Man sitting on bed talking to the doctor about prostate cancer treatment

Prostate Cancer Treatment

Prostate Cancer Treatment

Last Section Update: 03/2024

Contributor(s): Maureen Williams, ND

1 Introduction

Summary and Quick Facts for Prostate Cancer Treatment

  • Prostate cancer is common and can often be treated effectively in its early stages. For many men, immediate treatment may not be necessary.
  • This protocol will help you understand the different stages of prostate cancer and what treatments may be needed. Learn about dietary and lifestyle changes, and supplements that may complement a treatment approach.
  • Various preparations of lycopene and green tea supplements have been shown to benefit men with prostate cancer in clinical trials.

Roughly one in five men in the United States will be diagnosed with prostate cancer during their lifetime (NCI 2017c; Pollock 2015). Although prostate cancer can be deadly if it spreads to other organs, it is quite treatable if detected early (NCI 2018b; McLeod 2004). Surgery, radiation, and medicines to block hormones are common treatment options (NCI 2018b; NCCN 2017b). Researchers are continually working to make these treatments better and improve outcomes for men with prostate cancer (Ho 2017; Counago 2017; Montgomery 2016; Roth 2008; Holmboe 2000).

Many medical innovations in prostate cancer diagnosis and treatment have emerged in recent years. Advanced imaging techniques such as multiparametric MRI have made diagnosis more accurate and treatment more precise (Ahmed 2017; Bagheri 2017). New blood tests provide patients and doctors with information to better select appropriate treatment strategies (Tosoian, Druskin 2017). Immunotherapy, which has been a huge advance for cancer care in general, is currently an active and promising area of prostate cancer research (Bilusic 2017; Schepisi 2017).

While much discussion centers around specific treatments and diagnostics for prostate cancer, one of the most important aspects of a man’s journey through this disease is his involvement in decisions related to his care. It is important that men take an active, informed role in their prostate cancer care (Baade 2012). Obtaining accurate information is critical for men with prostate cancer—one study found that men who had greater knowledge about their options had better quality-of-life six months after treatment (Orom 2016). A man should work closely with his medical team to discuss key considerations, such as:

  • What treatment options are available for the level of disease he has;
  • Whether to pursue aggressive treatment options, such as surgery or radiation, or a less aggressive approach, called active surveillance, in early prostate cancer; and
  • What are the potential risks and benefits of each treatment option.

This protocol will provide the information that patients and their loved ones need to be informed and active in decisions related to prostate health. You will learn about current tools for finding and diagnosing prostate cancer, and treatment options for all stages of the disease. This protocol also includes details on many promising new treatments being developed, as well as integrative, natural interventions that may complement conventional therapy.

This protocol focuses on prostate cancer treatment. More information about prevention is available in the Prostate Cancer Prevention protocol. Readers are encouraged to review both of these protocols, as well as other relevant cancer-related protocols:

2 Background

The Prostate Gland

The prostate gland is part of the male reproductive system and produces an important fluid component of semen. Prostatic fluid helps sperm travel through the female reproductive tract to the egg for fertilization (NCCN 2016b; Schjenken 2015).

The prostate is located just below the bladder and surrounds part of the urethra, the tube that carries urine out of the bladder (NCCN 2016b). Because the prostate sits adjacent to the rectum, it can be felt during a manual procedure called digital rectal exam.

The prostate gland needs testosterone to function properly (NCI 2017c). Testosterone and its metabolite dihydrotestosterone stimulate prostate growth, particularly during puberty (Wilczynski 2015).

Pre-cancerous and Non-cancerous Conditions of the Prostate

As men age, growth of the prostate can cause restriction or partial blockage of the urethra (NCI 2017a). This condition, called benign prostatic hyperplasia (BPH), is common in older men and is not a form of cancer. Prostatitis, or inflammation of the prostate, is another non-cancerous condition that is more common in younger men (Mayo Clinic 2016). Prostatitis is often caused by a bacterial infection, but other factors, including autoimmune processes, may also contribute (Mayo Clinic 2016; Vaidyanathan 2008).

Prostate cells can take on some of the features of cancer cells in a condition called prostatic intraepithelial neoplasia, or PIN, which is diagnosed via prostate biopsy (Voltaggio 2016; Packer 2016). High-grade PIN denotes cells that look abnormal and is considered precancerous. Men with multiple sites of high-grade PIN detected on biopsy are more than twice as likely to develop prostate cancer as men without PIN (Bjurlin 2014; Cicione 2016). Although estimates vary, the risk of prostate cancer after a diagnosis of multiple-site high-grade PIN may be higher than 30% (Cicione 2016).

Because of its precancerous nature, careful monitoring is often recommended in cases of high-grade PIN (Bjurlin 2014; Cicione 2016). Men with PIN may benefit from lifestyle and dietary changes and targeted supplements aimed at preventing cancer from developing (Cheetham 2011).

Prostate Cancer

Most prostate cancers are of a type called adenocarcinomas (NCCN 2016b). Adenocarcinomas develop in the prostate when normal glandular cells become cancerous (Packer 2016). Gene mutations accumulate and promote abnormal prostate cell division, eventually leading to cancer development. As the tumor progresses, it causes alterations in surrounding tissues, making its growth easier (Yu 2017; Levesque 2017).

When a tumor is no longer confined to the prostate gland, it may spread to other nearby structures, such as the seminal vesicles (Small 2015). It can also spread to the urethra, rectum, and bladder (Zardawi 2016; Abbas 2011; Hallemeier 2010). In later stages, prostate cancer is found in the lymph nodes and distant parts of the body such as the bones, lungs, or liver (Rycaj 2017; Macedo 2017). The disease does not progress in the same manner, nor at the same rate, in all men (Pollard 2017; Peisch 2017).

3 Causes and Risk Factors

The risk of prostate cancer, like many other forms of cancer, increases with age. Forty-year-old men have a 2.3% chance of being diagnosed with prostate cancer by age 60. For 70-year-old men, the 20-year risk of prostate cancer is 9.5% (CDC 2015).

African-American men have a higher risk of prostate cancer than Caucasian men (Wells 2010; Zhang 2013). In one study of almost three million servicemen, African Americans were nearly three times more likely to be diagnosed with prostate cancer (Wells 2010). According to the Centers for Disease Control and Prevention (CDC), about twice as many African Americans die from prostate cancer as Caucasians (CDC 2017). In contrast, Asian Americans have a lower risk of prostate cancer (Tran 2016; CDC 2017).

Men with a family history of prostate cancer and those who have specific gene mutations have an increased risk of prostate cancer (Helfand 2015; Chen 2017; Cheng 2017). For instance, mutations in the BRCA1 or BRCA2 genes increase prostate cancer risk (Lecarpentier 2017). The likelihood of developing prostate cancer before age 65 is more than eight-fold higher in men with mutations in the BRCA2 gene. The presence of BRCA2 gene mutations predict a lifetime prostate cancer risk of 30–40% and is associated with more aggressive forms of cancer. While BRCA1 mutations have also been correlated with increased prostate cancer risk, the relationship is not as strong as with BRCA2 mutations (Costa 2017; Mateo 2017).

Obesity may be associated with increased risk for advanced prostate cancer (Vidal 2017; Rundle 2017). In a large prospective study of over 25,000 men, obesity was associated with increased prostate cancer risk in non-Hispanic white men and African-American men, but the association was stronger in African-American men than men of other races (Barrington 2015).

Dietary factors have been linked to prostate cancer risk. Greater intake of red meat (especially that cooked at high temperatures) and animal fats have been linked to increased prostate cancer risk (Nelson 2014). On the other hand, a healthy diet has been linked to lower risk of prostate cancer and better outcomes in several studies. Studies have shown that a diet rich in plant-based foods may be protective against prostate cancer (Perez-Cornago, Travis 2017; Peisch 2017). For a more thorough evaluation of dietary prostate cancer risks, review the Prostate Cancer Prevention protocol, specifically, the section titled “Impact of Diet on Prostate Cancer Risk and Mortality.”

Research suggests that smoking is a risk factor for many cancers, including cancer of the prostate (Tang 2017; Sato 2017; Jones, Joshu 2016). Smokers are more likely to be diagnosed with more advanced prostate cancer (Ho 2014), develop fatigue while using docetaxel (Taxotere) (a chemotherapy drug commonly used to treat prostate cancer) (Bergin 2017), and have complications such as pneumonia and unplanned intubation after prostate surgery (Byun 2017).

Gonorrhea (a sexually transmitted infection) is associated with increased prostate cancer risk (Lian 2015; Wang, Chung 2017; Vazquez-Salas 2016).

4 Signs and Symptoms of Prostate Cancer

With the widespread use of prostate cancer screening tests, over 60% of men with prostate cancer may not have any symptoms at the time of diagnosis. Instead, the only sign of the disease may be an elevated prostate-specific antigen (PSA) level. For some men, the tumor can be felt during a digital rectal examination (Small 2015).

Men with more advanced prostate cancer may have symptoms such as urination difficulties, discomfort in the pelvic area, and blood in the semen (Mayo Clinic 2018). Cancer that has spread beyond the prostate to other organs can cause other symptoms such as bone pain (NCI 2018b).

5 Diagnosis

Screening Tests

PSA and digital rectal exam. Until about 2008, doctors recommended that most men over 50 be screened for prostate cancer yearly with a PSA test along with a digital rectal exam (NCI 2017d; USPSTF 2008; NCI 2018a). PSA is a protein produced by cells of the prostate gland (NCI 2018a; Malatesta 2000), and high blood levels of PSA are often seen in men with prostate cancer. However, PSA levels can also be elevated as a result of benign prostate conditions, such as prostatitis and BPH (USPSTF 2008; NCI 2018a).

Controversy and new guidelines. Prostate cancer screening guidelines have been controversial (Wilt 2015; Etzioni 2014; Payton 2012; Tabayoyong 2015). As increasing numbers of men were being screened, critics became concerned that too many men were undergoing invasive diagnostic procedures only to find out they did not have cancer (NCI 2017d; USPSTF 2008; USPSTF 2017). A second concern was that some cancers detected during routine screening might not have become clinically significant in the man’s lifetime (Howrey 2013; Etzioni 2002; Andriole 2012).

In 2008, the United States Preventative Service Task Force (USPSTF) recommended against routine screening for men over 75 (USPSTF 2008). In 2012, they expanded this recommendation to men of all ages (Moyer 2012). A review of the literature from 2012 to 2016 found that the use of PSA testing had declined, and not as many prostate biopsies were being performed as previously (Lee, Mallin 2017).

As routine screening has declined, there are new concerns that men will be diagnosed in later and less treatable stages of prostate cancer (Lee, Mallin 2017; Eapen 2017; Fleshner 2017). The most recent draft of prostate cancer screening guidelines released by the USPSTF in 2017 states that “the decision about whether to be screened for prostate cancer should be an individual one” (Bibbins-Domingo 2017; USPSTF 2017). This statement highlights the importance of personal and informed decision-making when it comes to prostate cancer screening (Eapen 2017).

New screening tests. PSA testing and digital rectal exam have been the primary prostate cancer screening methods. Several variations of the basic PSA test, described below, have been developed to improve its usefulness (Saini 2016; Hatakeyama 2017).

The PSA level at a single time point may not be as informative as changes in PSA levels over time (Salman 2015; Adhyam 2012). PSA velocity measures how quickly PSA is rising, and PSA doubling time measures how long it takes for PSA levels to rise twofold (Ponholzer 2010; Loughlin 2014). Both doubling time and velocity have been primarily studied for monitoring prostate cancer after diagnosis. These tests can indicate how quickly a tumor is growing, whether the cancer has metastasized, and how the disease is responding to treatment (Howard 2017; Freiberger 2017; Vickers 2014).

Some PSA is free in the blood, and some is bound to, or complexed with, other proteins (NCI 2018a). The standard PSA test detects both forms, while a newer test measures free PSA, and complexed PSA can be calculated using these values (NCI 2018a; Brawer 1998; Brawer 2003). Complexed PSA, free PSA, and tests that include information about both may provide a more accurate reflection of prostate cancer activity than total PSA alone (Wang, Li 2017; Strittmatter 2011; NCI 2018a).

Another version of the PSA test looks at a precursor form of PSA called pro-PSA (Peyromaure 2005; Ito 2014; Ayyildiz 2014). This form of PSA may be better than total PSA at determining which men with borderline total PSA may really have cancer (Boegemann 2016). The Prostate Health Index (PHI) is a test that combines information from total PSA, free PSA, and pro-PSA (Loeb, Catalona 2014). This test was approved by the Food and Drug Administration (FDA) in 2012, for men age 50 and older with a total serum PSA between 4 and 10 ng/mL and a normal digital rectal exam, to reduce the number of unnecessary prostate biopsies (Loeb, Catalona 2014; Sartori 2014). One recent study found that total PSA was 47% accurate for identifying men with cancer while the PHI test was 72% accurate (Tosoian, Druskin 2017).

While some research has focused on improving the PSA test, other research has developed completely new tests. For the PCA3 test, for example, urine is collected after a digital rectal exam (NCI 2018a; Martignano 2017). The cells in the urine are tested for the prostate cancer-specific gene PCA3 (Hessels 2003). PCA3 testing is not currently used as a general screening test. Instead, for men with high PSA levels but no cancer detected in a biopsy, PCA3 testing can help determine which men should have a repeat biopsy and which should be monitored using active surveillance (Rubio-Briones 2017; Wang, Chen 2017; Galasso 2010).

Diagnostic Tests

Doctors diagnose prostate cancer by examining tissue from a biopsy (Bjurlin 2014; NCCN 2016b; Small 2015). The biopsy is most often collected through the wall of the rectum. Typically, at least 12 cores (different areas) of tissue are removed to check all areas of the prostate (NCCN 2016b). Some men experience adverse effects or complications such as soreness, infection, or bleeding after prostate biopsy (NCCN 2016b; Bjurlin 2014; Jones, Radtke 2016).

Imaging techniques are commonly used during the biopsy procedure (Woodrum 2017). Transrectal ultrasonography uses sound waves to produce images of the prostate (NCI 2018b). The doctor uses these images to ensure biopsy samples are obtained from the targeted regions of the prostate (NCCN 2016b).

Doctors may also use magnetic resonance imaging (MRI) along with transrectal ultrasonography (Marks 2013; Woodrum 2017; NCI 2018b; Jambor 2017). MRI images are taken before the procedure to assess the patient’s risk of prostate cancer, possibly preventing unnecessary biopsies (Porpiglia 2017; Ahmed 2017). If a biopsy is needed, these highly sensitive MRI images can be used to identify the region of the prostate to target (NCCN 2016b), improving diagnosis of more dangerous forms of cancer (Bjurlin 2017). In a study that enrolled 601 men who were scheduled for prostate biopsy, MRI-guided biopsy identified greater than 30% more cases of high-grade prostate cancer than traditional biopsy methods (Meng 2016).

Prognostic Assessment

A prognostic test can help guide treatment decisions by providing information on how aggressive a tumor is or how likely it is to spread (Terada 2017). Tissue obtained during biopsy or surgery is analyzed by a pathologist who assesses the characteristics of the cells and determines the Gleason score (Litwin 2017). The Gleason scoring system has been used for decades to indicate how aggressive a tumor is and guide treatment decisions (Chen 2016; Slager 2003; Wright 2009; Humphrey 2004).

The Gleason Score

The Gleason score is an established system for grading tumors and plays an important role in treatment selection. To determine the Gleason score, a pathologist first analyzes tumor cells in a biopsy or surgery sample under a microscope to determine how much they differ from normal cells and express this as a number between one and five (NCI 2018b). Lower numbers indicate that the characteristics of the cells are closer to those of normal cells and higher numbers indicate that the cells have more cancerous characteristics. The pathologist assigns a number, or a grade, to the two areas that make up most of the tumor. The sum of these two numbers is called the Gleason score. The Gleason score can range from 2 to 10 (although only Gleason scores of 6 – 10 are reported clinically in most cases) (NCCN 2016c; ACS 2017). Also, the individual numbers are usually provided (such as 3+4=7). The number listed first is the grade that is most common in the tumor (ACS 2017).

Tumors that are Gleason score 6 or lower are likely to grow slowly and may not require invasive treatment right away (NCCN 2016b). Patients with higher Gleason score tumors have a worse prognosis and may benefit from more aggressive treatment plans (NCCN 2017b). In 2014, new guidelines were released for grouping patients by Gleason score (Gordetsky 2016; Epstein 2017):

  • Grade Group 1 = Gleason score ≤ 6
  • Grade Group 2 = Gleason score 3 + 4 = 7
  • Grade Group 3 = Gleason score 4 + 3 = 7
  • Grade Group 4 = Gleason score 8
  • Grade Group 5 = Gleason scores 9 and 10

This new grouping system was validated in a study in over 20,000 men undergoing radical prostatectomy. Using PSA levels alone as the measure of recurrence, the rates of 5-year survival without recurrence in men in Groups 1, 2, 3, 4, and 5 were 96%, 88%, 63%, 48%, and 26%, respectively (Epstein 2016).

A commonly used system of staging is called the TNM system. The “T” component describes how much the tumor has grown in and around the prostate gland; the “N” component of staging indicates whether the cancer has spread to lymph nodes; and the “M” component indicates whether the cancer has metastasized (NCCN 2016b; Small 2015).

After being diagnosed with prostate cancer, patients typically undergo further testing to determine whether the cancer has spread to the lymph nodes and other organs (ie, to assess their TNM status) (Bhindi 2017; Rodgers 2017). Selecting which type of additional testing is appropriate depends on each man’s clinical status. Men with higher PSA values or Gleason scores or larger tumors may be candidates for additional imaging such as a bone scan with technetium-99m, pelvic computed tomography (CT) scan, or pelvic MRI to check for cancer spread (NCCN 2016b). Men whose PSA is above 10‒20 ng/mL are often advised to undergo the technetium-99m bone scan. The American College of Radiology has developed guidelines to help guide the selection of imaging tests for men with prostate cancer, based on variables such as “T” stage, Gleason score, PSA level, and number of positive biopsy cores (National Guideline 2016).

One challenge with both MRI and CT scans is they have a relatively high rate of inaccurately identifying the extent of the disease, which may lead to a suboptimal course of treatment. The development of techniques such as multiparametric MRI and sophisticated types of positron emission tomography (PET) scans has expanded the repertoire of tools available to physicians for use during prostate cancer evaluation (Bednarova 2017; Fulgham 2017). Results from these tests can be used to assess cancer stage and guide treatment decisions (NCCN 2017b; NCCN 2016b; Bhindi 2017; Rodgers 2017). Other techniques combining PET and MRI technologies have been investigated; these newer modalities may improve treatment planning in the near future (Eiber 2013). However, as previously mentioned, each man’s clinical status and unique situation must be taken into consideration when determining which testing strategies are optimal.

Importantly, given the numerous and complex strategies available for investigating the extent of prostate cancer, it is important that each patient undergo careful and thoughtful evaluation. Some experienced physicians have noted that lack of attention to detail in assessing a man’s clinical status may lead to inaccurate TNM staging and thus suboptimal treatment. Men in the midst of prostate cancer diagnosis and staging should ask lots of questions of their medical team and be sure they are confident that sufficient detail is being gathered to carefully plan their treatment.

Nomograms are tools that combine available clinical information from large numbers of patients and use mathematical calculations to estimate an individual’s risk of various events. In the case of prostate cancer, these events may include the spread (metastasis) of prostate cancer or mortality after specific treatments. Nomograms, when used appropriately by knowledgeable clinicians, can help individualize the treatment decision-making process (NCCN 2016b; Beauval 2017; Kim 2017; Lowrance 2009; Caras 2014). Nomograms can be informative about many aspects of prostate cancer care, including estimating the need for biopsy and the choice for adjuvant therapy (Caras 2014). However, because it is difficult to standardize these assessments (ie, different nomograms are appropriate for different patients), practitioners may prefer different nomograms or interpret them slightly differently.

In recent years, imaging studies, such as MRI, have been incorporated into prostate cancer nomograms (Caras 2014). Several research studies have revealed that incorporating multiparametric MRI into nomograms could improve their predictive value (Watson 2016). While nomograms may be very useful in addressing a specific question, they also have several shortcomings (eg, cost), and they are not perfectly accurate. Moreover, nomograms are only valid if used on a treatment population that is similar to the population from which the nomogram data were collected (Caras 2014). Given the complexity of properly employing nomograms, they may be underutilized, even though they have demonstrated value when used appropriately. Men in the treatment-planning stages of prostate cancer management should ask their care team whether these valuable tools have been incorporated into the decision-making process for their care.

6 Conventional Treatment

Locating an Experienced Prostate Cancer Physician

Working with a caring, experienced physician versed in the latest research and treatment approaches can make a remarkable difference in man’s prostate cancer journey. Therefore, a crucial initial phase of treatment is ensuring that you are working with a physician capable of delivering high-quality care aligned with the latest scientific evidence. The physicians listed below are regarded by many in the prostate cancer community as being skilled and highly qualified to provide top-notch care. (Note that this is not an inclusive list but rather encompasses some recognized prostate cancer experts known to Life Extension.)

Jeffrey Brady, MD   

  • Orlando, FL
  • 407-897-3499

Albert Chang, MD, PhD

  • Los Angeles, CA
  • 310-825-9775

Matthew Cooperberg, MD, MPH

  • San Francisco, CA
  • 415-353-7093

Amar Kishan, MD  

  • Los Angeles, CA
  • 310-825-9775

Laurence Klotz, MD, FRCSC  

  • Toronto, ON
  • 416-480-4673

Eugene Kwon, MD  

  • Rochester, MN
  • 507-405-2932

Brian Moran, MD

  • Westmont, IL
  • 630-654-2515

Gary Onik, MD

  • Fort Lauderdale, FL
  • 561-527-2380

Mark Scholz, MD

  • Marina del Rey, CA
  • 310-827-7707

Michael Steinberg, MD

  • Los Angeles, CA
  • 310-825-9775

John Sylvester, MD

  • Bradenton, FL
  • 941-748-4324

Nicholas Vogelzang, MD

  • Las Vegas, NV
  • 702-952-3400

Evan Yu, MD   

  • Seattle, WA
  • 855-557-0555

When diagnostic and staging information are available, the patient and his medical team can begin to consider treatment options (NCCN 2017b; Gillessen 2017; Small 2015) (see Table 1). For some men with early-stage, low-risk disease, an approach called active surveillance can be considered. In active surveillance, no treatment is administered and the prostate cancer is monitored carefully (Wilt 2017; Garisto 2017). Some evidence suggests treatment with 5-alpha reductase inhibitor drugs, like dutasteride and finasteride, which are used to treat benign prostatic hyperplasia (BPH, commonly known as “prostate enlargement”), may delay progression of low-risk prostate cancer. In a randomized controlled trial (REDEEM) that enrolled over 300 men undergoing active surveillance for low-risk prostate cancer across 65 sites in North America, treatment with dutasteride significantly reduced the risk of prostate cancer progression over a three-year period (Fleshner 2012, Wu 2020). Men with low-risk disease may stand to benefit from initiating therapy with a 5-alpha reductase inhibitor like dutasteride. Men in this situation should ask their doctor whether they are a good candidate for 5-alpha reductase inhibitor treatment. (More information about the role of 5-alpha reductase inhibitors in the context of low-risk prostate cancer is available in Life Extension’s Prostate Cancer Prevention protocol.)

If treatment is deemed necessary, surgery and various forms of radiation are common initial options (NCCN 2016b; NCCN 2017b; Small 2015). Those with more advanced disease or disease that has recurred after initial treatment may want to consider options such as chemotherapy, hormonal therapy, or immunotherapy (NCCN 2016b; Small 2015; NCCN 2017a).

Table 1: Initial Treatment Options Based on Disease Stage and Risk

Type of Prostate Cancer


Treatment Options

Low-risk disease

Small tumors confined to prostate
Gleason score ≤ 6
Gleason grade group 1
PSA < 10 ng/mL

  • Active surveillance
    • May include treatment with a 5-alpha reductase inhibitor (eg, dutasteride) in some cases
  • Radical prostatectomy
  • Radiation (EBRT or brachytherapy)

Intermediate-risk disease

Larger tumors confined to prostate
Gleason score = 7
Gleason grade group 2–3
PSA = 10–20 ng/mL

  • Active surveillance
  • Radical prostatectomy
  • EBRT, sometimes with hormone therapy
  • Brachytherapy

High-risk disease

Tumors that have grown beyond the prostate to local structures
Gleason score ≥ 8
Gleason grade group 4–5
PSA > 20 ng/mL

  • Radical prostatectomy, sometimes with hormone therapy
  • EBRT, typically with hormone therapy
  • EBRT plus brachytherapy, typically with hormone therapy

Progressive disease after initial therapy

Disease progression detected by PSA, digital rectal examination, or imaging

  • Radical prostatectomy for those previously treated with radiation
  • EBRT for those previously treated surgically
  • Brachytherapy
  • Hormone therapy
  • Cryotherapy
  • High-intensity focused ultrasound

Metastatic disease

Tumors that have grown beyond the prostate to the bladder, rectum, lymph nodes, or distant organs

  • Hormone therapy
  • Sipuleucel-T (Provenge)
  • Chemotherapy
  • Radiation therapy to metastases
  • Treatments for pain and other symptoms

EBRT=External beam radiation therapy; PSA=Prostate specific antigen
(Small 2015; NCCN 2017b)

Active Surveillance

Treatments such as surgery and radiation are invasive, with potential side effects and complications (Wilt 2017; Lee 2015). Men with low-risk prostate cancer have a good chance of living full lives without being affected by the disease, even without active treatment (Wilt 2017; Hamdy 2016). However, treatment with a 5-alpha reductase inhibitor, such as dutasteride, may reduce the risk of progression in some men with low-risk disease (Wu 2020). Men with low-risk prostate cancer should ask the physician who is managing their active surveillance if they are a candidate for treatment with dutasteride or another 5-alpha reductase inhibitor.

Active surveillance is a regimen of regular monitoring with PSA, digital rectal examination, and repeat biopsies (Garisto 2017; NCCN 2017b). With regular testing, the patient’s risk status can be monitored. If anything suspicious is detected, additional tests or an active treatment approach can be considered.

One recent study followed 731 men with prostate cancer who were randomly assigned to either active surveillance or surgery. After almost 20 years, there were no significant differences in rates of prostate cancer-related deaths or deaths from any cause in the two groups. Surgery was associated with more adverse events than surveillance, while surveillance was associated with increased likelihood of treatment for disease progression (Wilt 2017).

Another recent trial compared active surveillance, surgery, and radiation therapy in 1,643 men with low-risk prostate cancer. After an average of 10 years of follow-up, there were very few prostate cancer-related deaths in all three groups. Metastases were more common, but still rare (about 6%), in the active surveillance group compared to the other two groups (Hamdy 2016).

Patients under active surveillance may benefit from implementing dietary and lifestyle practices associated with prostate health. For example, both healthy diet and exercise can reduce the risk of disease progression during active surveillance (Galvao 2016). Supplements such as omega-3 fatty acids and vitamin D may also be helpful (Marshall 2012; Moreel 2014). In addition, new molecular tests such as Oncotype Dx and Promark may help patients and their medical teams feel more confident in the selection of active surveillance (Albala 2016; Ross 2016). (See the Novel and Emerging Strategies section of this protocol).

Deciding Among Treatment Options in Newly Diagnosed Prostate Cancer

When men are first diagnosed with prostate cancer, they, along with their medical team, face the task of deciding which initial treatment approach is right for them. The patient’s risk group plays a major role in this decision (Small 2015; NCCN 2017b).

But what about men for whom two or more options are equally appropriate? Some studies indicate that a patient’s treatment preferences may be overshadowed by their doctor’s recommendations (Scherr 2017). This suggests the value of talking with more than one type of prostate cancer specialist during the decision-making process. Radiation oncologists, who do not perform surgery, and urologists, who are surgeons, may present treatment options differently (Kim 2014; Jang 2010).

Patients can develop realistic expectations by asking questions when they meet with their medical team. Lack of complete information frequently leads men to underestimate their life expectancy with active surveillance and overestimate the gain in life expectancy with surgery or radiation (Xu 2016). Patients who discuss the risks and benefits of all treatment options with their medical team tend to be more satisfied with their ultimate decision (Davison 2003; Holmes 2017).

Online resources and advocacy groups can also help men stay involved and informed. Some decision aids have been specifically designed to support men through this process (Gorawara-Bhat 2017; Christie 2015), and men who use these tools are better able to ask critical questions about the treatments recommended by their medical team (Holmes-Rovner 2017; Jones, Hollen 2016).

Radical Prostatectomy

One common treatment option for prostate cancer is a type of surgery called radical prostatectomy (NCCN 2016b). Radical prostatectomy is mainly used when cancer is believed to be confined to the prostate gland (NCCN 2017b). According to the CDC, about 138,000 radical prostatectomies were performed in the United States in 2010 (CDC 2010).

During the procedure, the prostate gland is removed along with the seminal vesicles and sometimes other affected tissues in the region (NCCN 2016b; NCI 2018b). In the most common form of prostatectomy, called retropubic prostatectomy, lymph nodes can be removed if necessary, and nerves required for erection can be spared if they are not affected by the cancer (NCI 2018b; NCCN 2016b; Tosoian 2012; Masterson 2006; Goyal 2007).

Prostatectomies can also be performed laparoscopically to shorten recovery time. In this procedure, surgical tools are inserted through several small incisions. Laparoscopic surgery can be conducted using robotic arms to make very careful cuts, thereby reducing the risk of damage to healthy tissues (NCCN 2016b; Ku 2017). One study reported that robotic-assisted surgery was more effective than unassisted laparoscopic surgery at preventing PSA level rises that could indicate recurrence (Lee, Seo 2017).

Most men experience short-term urinary incontinence or sexual dysfunction after surgery (NCCN 2016b). Improvements in surgical techniques have reduced the number of men who experience long-term complications (Small 2015; Wallis 2017). The risk of long-term problems varies greatly based on individual characteristics, extent of the cancer, and skill of the surgeon (Goldenberg 2017). For instance, older patients or those whose nerves have been affected by the cancer are more likely to experience long-term erectile problems after surgery (NCCN 2016b).

Radiation Therapy

Men with prostate cancer that has not spread to surrounding tissues are commonly treated with radiation therapy. Radiation is also a valuable tool for recurrent disease and disease that has spread to lymph nodes (Small 2015; NCCN 2017b; NCCN 2016b). Radiation destroys cancer cells but can also cause damage to nearby healthy cells (NCI 2010).

External-beam radiation therapy uses a machine to deliver beams of photons to the prostate gland (NCCN 2016b). The radiation is carefully targeted to the cancer cells using digital imaging (NCI 2018b). Intensity-modulated radiation therapy is an advanced form of radiation that uses many carefully-calculated doses applied from various angles. This approach decreases the doses of radiation that reach normal organs and tissues. Intensity-modulated external-beam radiation has become the standard modality of radiation therapy for prostate cancer (Moon 2017).

Stereotactic body radiation therapy is a type of intensity-modulated radiation therapy used in recent years to treat men with localized prostate cancer. One advantage of this approach is that the treatment can be completed in about five visits (NCCN 2016b; Koskela 2017). Although this approach is a safe and effective way to treat prostate cancer, trials are currently under way to compare stereotactic body radiation therapy with other approaches (Kishan 2017; Kim 2016).

Intensity-modulated radiation therapy uses photon beams to irradiate the prostate, while a form of radiation therapy called proton therapy uses proton beams (NCCN 2016b). Proton beams release most of a dose of radiation at a specified depth. This may allow the use of higher doses of radiation without causing side effects involving nearby organs such as the bladder and rectum (Moon 2017). One recent study that enrolled 1,375 patients treated with proton therapy found that PSA levels remained low five years after treatment in 99%, 91%, and 86% of low-, intermediate-, and high-risk patients, respectively (Takagi 2017). Although this method is promising, long-term studies comparing it to intensity-modulated radiation therapy are needed (Magnuson 2017; Moon 2017).

Brachytherapy is another option for men with some early stage prostate cancers (NCCN 2017b). Brachytherapy involves the use of radiation-emitting devices called seeds that are about the size of a grain of rice. Using imaging techniques to guide placement, 40 to 100 seeds are implanted permanently or temporarily within the prostate. Because the radiation is delivered directly into the tumor, the dose of radiation can be high with minimal risk to healthy tissues (NCCN 2016b; Stish 2017). For patients with higher-risk cancer, brachytherapy can be combined with external beam radiation therapy and hormonal therapy (NCCN 2017b; Hannoun-Levi 2017).

Radiation therapy can cause short-term and long-term urinary, bowel, and sexual function symptoms (Lee 2015). External beam radiation therapy can also cause damage to the skin (NCCN 2016b). When data from many studies were analyzed together, patients treated with radiation were found to be more likely to have bowel symptoms, but less likely to have urinary or sexual function problems, compared with patients treated with surgery (Lardas 2017; Wallis 2017). New devices such as the SpaceOAR Hydrogel System, which creates a physical space between the prostate and rectum during radiation therapy, may increase protection of healthy tissues (Hamstra 2017; Wolf 2015; Augmenix 2017).

Refer to the Cancer Radiation Therapy protocol for more general information.


Cryotherapy, also called cryosurgery or cryoablation, is a newer treatment in which argon gas is sent through very thin needles into the prostate to freeze the tumor (NCCN 2016b). Cryotherapy is an option that is typically considered when radiation fails to completely destroy the cancer (NCCN 2017b); however, existing data on cryotherapy as an initial treatment are encouraging (Bahn 2012; Garcia-Barreras 2017; Durand 2014). One study compared cryotherapy with external beam radiation in men with newly diagnosed cancer that had not spread beyond the prostate. There was no difference between the two approaches in prostate cancer survival, and patients who received cryotherapy had fewer positive biopsies after three years (Donnelly 2010).

One innovative physician, Gary Onik, MD, has had success treating localized prostate cancer with focused cryotherapy. The approach taken by Dr. Onik and his team involves carefully mapping the location of cancer in the process via a technique called three-dimensional prostate-mapping biopsy. Then, after the tumors have been precisely located, patients are treated with focal cryoablation, in which targeted cryotherapy is applied to the cancerous tissue. Dr. Onik’s team conducted a study in which they used this technique on 46 men.

Impressively, biochemical disease-free survival was 89% after 10 years of follow-up, and the rate of biochemical disease-free survival did not differ by initial risk group. (This is important because men with higher-risk prostate cancer usually have a higher rate of recurrence and death from prostate cancer). Moreover, local recurrence was considerably less common in the group who underwent three-dimensional prostate mapping (4%) compared with those who underwent transrectal ultrasound (TRUS, 33%) (Onik 2014). A more comprehensive review of Dr. Onik’s pioneering work is available in the June, 2016 issue of Life Extension Magazine®, in an article titled “Major Advance in Screening and Treating Prostate Cancer.”

Hormone Therapy

Because androgens (male sex hormones) stimulate the growth of some prostate cancers, various types of hormone therapies are used to interfere with their actions (NCCN 2016b). Some hormone therapies stop the body from producing androgens, mainly testosterone, while others block the effect of testosterone on cancer cells (NCCN 2016b; NCI 2018b). Hormone therapy is a valuable tool used in all stages of prostate cancer except early low-risk disease (NCCN 2017b).

Hormone therapies targeting luteinizing hormone-releasing hormone (LHRH) prevent the testicles from making testosterone. Leuprolide (Lupron), goserelin (Zoladex), histrelin (Vantas), triptorelin (Trelstar), buserelin (Suprefact), and degarelix (Firmagon) are examples of such medications (NCCN 2016b; NCI 2018b). Another hormonal strategy for reducing testosterone is the use of certain forms of estrogens. Surgical removal of the testicles (orchiectomy) is used in some cases to dramatically reduce the amount of testosterone in the body (NCCN 2017b).

Ketoconazole (Nizoral), a well-known antifungal medication, is sometimes used for its ability to inhibit production of testosterone at several locations, including the adrenal glands (NLM 2017; NCCN 2016a; NCI 2018b). Abiraterone (Zytiga) is another androgen synthesis inhibitor approved by the FDA in 2012 for use in men with metastatic castration-resistant prostate cancer, a term referring to prostate cancer that has progressed despite testosterone-lowering therapy (Maluf 2012). Abiraterone plus the corticosteroid prednisone is used either before or after chemotherapy, and may be combined with other hormone therapy (NCI 2013; Fizazi 2012; James 2017; Fizazi 2017).

Antiandrogens block testosterone receptors on tumor cells. Bicalutamide (Casodex), flutamide, nilutamide (Nilandron), and enzalutamide (Xtandi) are examples of antiandrogens (NCCN 2016b; NCCN 2017b).

Apalutamide (Erleada), a nonsteroidal antiandrogen medication, was initially FDA-approved to treat non-metastatic castration-resistant prostate cancer in 2018, and was further approved in 2019 for patients with metastatic castration-sensitive prostate cancer (FDA 2019). Apalutamide is administered alongside androgen deprivation therapy or in those who have already undergone bilateral orchiectomy and has been shown to improve overall survival as well as progression-free survival (Uemura 2022; Lowentritt 2022). The phase III TITAN trial, which enrolled 1,052 patients with metastatic castration-sensitive prostate cancer, randomized patients to receive 240 mg apalutamide daily or placebo alongside androgen deprivation therapy. Those receiving apalutamide displayed a 33% reduced risk of death, 52% reduced risk of disease progression, and 61% reduced risk of beginning chemotherapy compared with placebo (Chi 2019). In the phase III SPARTAN trial, 1,207 patients with non-metastatic castration-resistant prostate cancer and a prostate-specific antigen doubling time of 10 months or less were assigned in a 2:1 ratio to receive 240 mg apalutamide daily or placebo alongside androgen deprivation therapy. Compared with placebo, the apalutamide group displayed significant increases in median metastasis-free survival time (40.5 months vs. 16.2 months), overall survival length (73.9 months vs. 59.9 months), and progression-free survival time (40.5 months vs. 14.7 months), as well as a 37% reduced risk of beginning chemotherapy (Smith 2018).

The side effects of hormone therapy can vary from patient to patient and depend on the exact therapy used (NCCN 2016b). In general, hormone therapies can cause erectile dysfunction, hot flashes, mood changes, weight gain, loss of muscle, breast growth, and fatigue (NCCN 2016b; NCI 2018b; Gilbert 2017). Long-term use of hormone therapies can weaken the patient’s bones and increase the risk of diabetes and heart disease (NCCN 2016b; Gupta 2017; Thomsen 2017).

The Importance of Administering LHRH Agonists on Time

LHRH agonists are often used to maintain low levels of testosterone for men with advanced prostate cancer. However, a retrospective analysis of nearly 23,000 prostate cancer patients treated with LHRH agonists found between 27% and 84% of the treatments were given later than recommended. This result is consistent with another large study that also found 27% of treatments were given late (Twardowski 2020). The medication is delivered via injection or implant, with different available formulations that can last one to six months, or even up to a year (Meani 2018; Johns Hopkins 2020). However, after that time period is past, testosterone levels begin to rise again. Patients with late injections tended to exceed recommended testosterone levels more than patients whose injections were given on time (Crawford 2020).

Furthermore, physicians were less likely to measure testosterone levels, which they checked only 13% of the time, instead relying on PSA levels (83% of the time), despite the recommendation that patients on LHRH agonists have testosterone levels monitored periodically. As evidence suggests maintaining low testosterone levels offers survival benefits for those with prostate cancer, it is important that those receiving LHRH agonists ensure they get their injections in a timely manner and have their testosterone levels monitored (Crawford 2020).


Chemotherapy is an option for men with castration-resistant metastatic cancers (NCCN 2017b). Docetaxel is a well-established and commonly used chemotherapy drug in prostate cancer treatment regimens. Newer data on docetaxel suggest the drug may also help men with tumors that still respond to hormone therapy (in other words, are not castration-resistant), particularly those with metastases or high-risk non-metastatic cancer (NCCN 2017b; Patrikidou 2017; Puente 2017; James 2016). In the CHAARTED trial, docetaxel extended average survival by slightly over one year in men being treated with hormone therapy (Sweeney 2015). Common side effects of docetaxel include diarrhea, nausea, vomiting, and loss of appetite; fatigue and weakness; low white blood cell counts and fever; numbness, tingling, or burning in the hands and feet; hair loss; and mouth sores (NCCN 2016b; Bergin 2017; ACS 2016).

In 2010, the FDA approved the chemotherapy drug cabazitaxel (Jevtana) for men whose cancer is progressing despite previous treatment with a regimen containing docetaxel (NCCN 2017b; Eisenberger 2017). Researchers are investigating how to manage the side effects, optimize the dose, and select the right patients for this drug (Eisenberger 2017; Patel 2017). Mitoxantrone (Novantrone) is another FDA-approved chemotherapy drug available for patients who cannot tolerate docetaxel or cabazitaxel (NCCN 2017b).

Refer to the Chemotherapy protocol for more general information.


As of late 2017, the only FDA-approved immunotherapy for prostate cancer is sipuleucel-T (NCCN 2016b; Silvestri 2016). Sipuleucel-T is a treatment option for men with metastatic castration-resistant prostate cancer. White blood cells from the patient are treated in the lab with a protein that helps them recognize and attack cancer cells. The cells are then returned to the patient’s body (Virgo 2017; NCI 2018b). In a randomized controlled trial, men treated with sipuleucel-T lived about four months longer than controls (Small 2006). In a recent phase-II clinical trial, sipuleucel-T caused a greater antitumor immune response when the treatment occurred before hormone therapy (Antonarakis 2017). Further studies will be needed to determine whether this therapy can be more effective before the development of castration-resistant disease.

Antibody-based Therapy

Ipilimumab (Yervoy), a monoclonal antibody that targets the immune checkpoint CTLA-4, was evaluated in a phase 3 study of 799 men with advanced prostate cancer and bone metastases who had already been treated with the chemotherapy drug docetaxel. Participants received radiation therapy to one or more bone metastases followed by either ipilimumab or placebo. Although there was no survival advantage with ipilimumab in the first year following treatment, additional follow-up revealed that ipilimumab significantly improved long-term survival. In years two through five after treatment, overall survival was better with ipilimumab than placebo (25% vs. 17% at year two, and 8% vs. 3% at year five) (Fizazi 2020).

Treatment of Bone Metastases

In addition to general prostate cancer treatments such as chemotherapy and hormone therapy, there are several options that specifically treat bone metastases. External beam radiation can be targeted to the bones (NCCN 2017b). Radiopharmaceuticals such as radium-223 naturally accumulate in areas of the bone with metastases and destroy cancer cells (NCI 2018b; Sartor 2014). Other drugs, such as denosumab (Prolia) and zoledronate (Aclasta), strengthen bones affected by cancer or weakened through cancer treatment and can help prevent fractures (Traboulsi 2017; Hegemann 2017; Israeli 2008).

Bone Loss and Prostate Cancer – A Complex Relationship

Bone fractures and vertebral body deformity or collapse from weakened bones are a major cause of morbidity and even death in patients with advanced prostate cancer (Matthew 2001; Johnson 2021). Their bones can be weakened both by bone metastases and osteoporosis, which is loss of bone mineral density. Since these patients are typically older and may require hormonal therapy, they are vulnerable to bone loss from their prostate cancer treatment and the normal aging process (Bubendorf 2000; Kim 2019). Even before starting hormonal therapy, many men diagnosed with prostate cancer already have some amount of bone loss (Parker 2020).

Bones are living tissues that contain cells, including osteoblasts and osteoclasts. There is a complex relationship between these cells and prostate cancer cells that have migrated to bone. This relationship is mediated by chemical messengers. Homing of the circulating prostate cancer cells is thought to occur through activation of the CXC-chemokine receptor type 4 on cancer cells, causing them to chemotaxis (ie, move in response to a chemical stimulus) to the bone. When prostate cancer cells spread to bone, they stimulate osteoblasts, which produce abnormal bone that is weak and prone to fracture. In addition to stimulating abnormal bone formation, however, the prostate cancer cells also secrete factors like interleukin-6 (IL-6) and parathyroid hormone-related peptide that ultimately lead to increased numbers and activity of the cells responsible for resorption of bone. These cells, called osteoclasts, contribute to bone breakdown and themselves release growth factors, such as transforming growth factor-beta, that promote further growth of prostate cancer cells. This process creates a vicious cycle of prostate cancer spread to bone, changes in bone metabolism, and further growth of the cancer cells (Walz 2019).

Under normal conditions, bone remodeling occurs with an equilibrium maintained between bone formation and resorption. Hormonal therapies that prevent the production of testosterone harm this equilibrium, resulting in rapid and severe bone loss. Consequently, these patients have an increased risk of bone fractures, bone pain, and impaired quality of life (Kim 2019).

For patients with advanced prostate cancer who are beginning hormonal therapy, clinical management should include monitoring for the early development of bone loss. Starting this process in the early phases of treatment allows for timely detection and, consequently, prompt intervention with measures to delay or prevent further loss of bone density (Kim 2019). Importantly, patients and their families should be educated about the importance of maintaining bone health. Making preservation of bone health a priority may help to maintain quality of life and achieve optimal disease outcomes (Saad 2021).

For all patients taking hormonal therapy for prostate cancer, lifestyle changes to maintain bone density are recommended. These include performing weight-bearing exercises, stopping smoking, and drinking no more than two alcoholic drinks per day (Parker 2020). Another important step is to consume sufficient calcium and vitamin D, which helps slow bone loss during treatment—especially in the first year. A daily amount of 1,000‒1200 mg calcium and 400‒1,000 IU vitamin D from both food and supplementation has been recommended and should be continued throughout treatment (Saad 2021). Caffeine intake should also be limited, as high amounts have been linked to decreased bone mineral density through a variety of mechanisms (Berman 2022).

Other potential interventions are treatment with an oral bisphosphonate or, if that is not tolerated, intravenous (IV) zoledronic acid (Reclast) or denosumab. Alternatively, they can be monitored with DEXA scanning (Parker 2020). Unlike a bone scan, which detects cancer that has spread to the bones, a DEXA scan evaluates bone mineral density. The DEXA scan is considered the gold standard for bone density testing but has limitations in patients with prostate cancer (Krugh 2022). This is due to the fact that these patients are generally older and can develop osteoarthritis in the spine, which when measured with a DEXA scan shows as an increase in bone mineral density. On the other hand, use of quantitative computerized tomography (QCT) to measure bone mineral density allows for measurement only in the central region of the vertebral bodies and can avoid the artificially high bone mineral density seen in DEXA due to osteoarthritis (Matthew 2001). Use of QCT instead of the DEXA scan, therefore, may be more reliable in older patients with prostate cancer.

Participating in a Clinical Trial

Some men may want to consider participating in a clinical trial. Many of the treatments described in the “Novel and Emerging Strategies” and “Integrative Interventions” sections are currently being tested. It is important to recognize that treatments under investigation might have significant side effects or might not be effective (NCI 2018b; Vieweg 2007). Whether the tested treatment is successful or not, all clinical trials help inform future patient care. Men who want to learn more about ongoing clinical trials can consult with their medical team. The following online resources may also be helpful:

  1. National Comprehensive Cancer Network (NCCN):
  2. National Cancer Institute:
  3. American Cancer Society:

Testosterone Replacement Therapy in Prostate Cancer

Testosterone deficiency affects around a quarter of men over age 40 and can considerably undermine quality of life (Liu 2022; Higano 2022). Supplemental testosterone, or testosterone replacement therapy (TRT), can alleviate symptoms attributable to low testosterone and improve quality of life in men with low testosterone levels (Hudson 2023). Whether or not testosterone replacement is appropriate for men with a history of localized prostate cancer remains controversial.

Historically, medical professionals have warned against testosterone replacement for men who have, or have had, prostate cancer (Polchert 2021). This cautious approach has been due to concern that testosterone therapy might stimulate prostate cancer growth (Higano 2022; Bhasin 2023). However, the understanding of the association, or lack thereof, of testosterone with prostate cancer has evolved (Bhasin 2023; Morgentaler 2009), and accumulating observational evidence suggests testosterone replacement in men who have been definitively treated for localized prostate cancer is not associated with recurrence (Polchert 2021; Kardoust 2019; Sarkar 2020). Men who have undergone a radical prostatectomy for localized prostate cancer and are considering TRT should have an undetectable PSA before initiating TRT. Those who have undergone other types of definitive treatment, such as radiation or ablation, should discuss with their healthcare team whether TRT may be appropriate as consensus has yet to be reached regarding how best to identify men who are ideal candidates for TRT in this setting (Higano 2022). As of early 2024, a randomized trial is ongoing to assess the safety and efficacy of testosterone therapy in men who have been treated for localized prostate cancer (Bhasin 2024).

Evidence is also accumulating to suggest that testosterone therapy in men with untreated prostate cancer undergoing active surveillance is not associated with increased risk of proceeding to active therapy (Ory 2016; Kaplan-Marans 2024). Randomized trials are needed to assess the safety and efficacy of testosterone replacement in this setting.

For men with advanced/metastatic prostate cancer, testosterone replacement is not advised for the purpose of addressing symptoms of low testosterone (Chedrawe 2022). Testosterone therapy may be used as part of a treatment regimen called bipolar androgen therapy, or BAT. In BAT, testosterone replacement is cycled with androgen deprivation (testosterone suppression) in an attempt to make prostate cancer cells more sensitive to the effects of androgen deprivation therapy. BAT may also improve quality of life for some patients. This approach remains investigational as of early 2024 and may only be available at a few university-level prostate cancer specialty centers or through participation in a clinical trial (Nabavi 2023; You 2022; Denmeade 2024; McKay 2024).

For men with prostate cancer or a history of prostate cancer, the decision to initiate testosterone must be made in consultation with a qualified healthcare provider who can help weigh the potential risks and benefits.

A more detailed discussion of testosterone in the context of prostate cancer is included in Life Extension’s Male Hormone Restoration Protocol.

7 Novel and Emerging Strategies

Improvements to Conventional Treatments

Commonly used treatments such as radical prostatectomy, radiation, and hormone therapy are constantly being reviewed and refined to improve patient survival and quality of life (NCCN 2017b). For example, identifying patient groups that are most likely to benefit from specific treatments is an active area of research. Recent clinical data suggest radical prostatectomy might be helpful even for men with advanced or high-risk disease (Weiner 2017; Gandaglia 2017; O'Shaughnessy 2017). Surgery may be particularly effective in this patient group when used in conjunction with radiation therapy (Fahmy 2017; NCCN 2017b).

Researchers are also developing new evidence regarding the optimal order and combinations of various treatments. As described earlier, docetaxel may be more effective when used before resistance to testosterone-lowering therapy develops (Estevez 2016). Other research is addressing issues such as which hormone therapy should be used first and when it should be started (Moul 2015; Dijkstra 2016; Ho 2017; Chu 2015).

New medications for treating prostate cancer are being studied. A newer second generation of hormone therapies is in development (Wadosky 2016; Bambury 2016; Petrunak 2017). Seviteronel, also known as VT-464, is an androgen synthesis inhibitor that is undergoing fast-track review by the FDA for approval in patients with metastatic castration-resistant disease (Norris 2017; Teply 2016; Pharmacutical Technology 2017).

Darolutamide (Nubeqa) is a hormone therapy belonging to a class of antiandrogen drugs. It exerts its effects by blocking the androgen receptor, preventing cells from responding to testosterone. Darolutamide is indicated for the treatment of patients who have prostate cancer that has not spread to distant sites in the body and that continues to grow even after testosterone levels have been lowered (Bayer Healthcare Pharmaceuticals Inc. 2021).

A recent study published in the New England Journal of Medicine investigated whether the addition of darolutamide to testosterone-lowering therapy and the chemotherapy drug docetaxel would help patients with prostate cancer that had already spread to distant sites but that exhibited slowed growth in response to lowered testosterone levels. The investigators specifically looked at whether patients given darolutamide lived longer than those on the same treatment regimen but without darolutimide (Smith 2022).

The investigators found that of the 1,306 patients enrolled in the study, those who received darolutamide lived significantly longer than those who did not. Moreover, even though they had taken an additional medication, the darolutamide group did not suffer from higher numbers of side effects (eg, abnormally low blood counts). Furthermore, they were able to go longer before their cancers stopped responding to testosterone-lowering therapy. These results support using a combination of darolutamide, testosterone-lowering therapy, and docetaxel to treat patients with metastatic hormone-sensitive prostate cancer (Smith 2022).

High-Intensity Focused Ultrasound

High-intensity focused ultrasound (HIFU) is being tested in men with newly diagnosed prostate cancer and those with cancer recurrence after radiation (NCCN 2017b; Golbari 2017; Garcia-Barreras 2017; Crouzet 2017). In this approach, ultrasound is focused on the tumor and its concentrated energy destroys the targeted tumor cells (NCCN 2016b; NCI 2018b; Kim 2008; Malietzis 2013).

HIFU is currently approved by the FDA for prostate tissue ablation, but is not specifically approved as a treatment for prostate cancer (Nelson 2015). HIFU may cause fewer side effects than radical prostatectomy, and initial studies suggest it may be equally effective in low-risk patients; however, more research is needed (Garcia-Barreras 2017; Kanthabalan 2017; Jones 2017; Albisinni 2017).

Vascular-Targeted Photodynamic Therapy

Vascular-targeted photodynamic therapy involves injection of a photosensitizing, or light-sensitizing, drug. Small laser fibers are inserted into the prostate to activate the drug locally, and the activated drug destroys blood vessels supporting the tumor (NCCN 2016b).

A phase-III clinical trial evaluated vascular-targeted photodynamic therapy in men with low-risk prostate cancer. Side effects were rare, and fewer men in the photodynamic therapy group (about 30%) than the active surveillance group (about 60%) had disease progression after two years (Azzouzi 2017). Moreover, almost half of the patients that underwent photodynamic therapy, compared with only 14% in the active surveillance group, had a cancer-free biopsy sample two years after treatment (Stone 2017).

Targeted Therapies

Targeted therapies are designed to block or inhibit specific molecules that help cancer grow. Olaparib (Lynparza) is a type of drug that interferes with a protein called poly ADP ribose polymerase, or PARP, that helps cancer cells repair their DNA (NCCN 2017b). Olaparib and other PARP inhibitors may be effective treatments for men with tumors that rely on this DNA repair function (Ramakrishnan Geethakumari 2017).

In a phase-II clinical trial, 88% of patients with defects in tumor DNA-repair genes responded to olaparib (Mateo 2015). Researchers are developing tests to identify patients who are likely to respond to olaparib and other targeted drugs (Goodall 2017). In 2016, the FDA granted olaparib “breakthrough therapy” designation for metastatic castration-resistant prostate cancer, which ensures its rapid review (Ramakrishnan Geethakumari 2017; Helleday 2016).

Another emerging therapy targets prostate-specific membrane antigen, or PSMA, which is highly concentrated on the surface of prostate cancer cells. Agents called PSMA ligands bind PSMA and carry a radioactive substance to destroy the prostate cancer cells (Eiber 2017; Kulkarni 2016).

In a recent study, 145 patients with advanced prostate cancer were treated with a PSMA ligand. Forty-five percent had reductions of at least 50% in their PSA levels (Rahbar 2017). Two other studies found PSA levels decreased in about 80–90% of patients after treatment with PSMA-directed radiotherapy (Baum 2016; Brauer 2017).


Immunotherapy, an approach that uses the patient’s own immune system to fight cancer, was named the “cancer advance of the year” by the American Society of Clinical Oncology in both 2016 and 2017 (Madan, Gulley 2017; Rijnders 2017; Burstein 2017; Dizon 2016). Sipuleucel-T was one of the first FDA-approved immunotherapies (Madan, Gulley 2017).

Cancer vaccines deliver a cancer-specific protein to the body and direct the immune system to target cells that contain that protein (Sayour 2017). A vaccine developed for prostate cancer called PROSTVAC was designed to trigger the immune system to attack cells that have PSA on their surface (Mandl 2014; DiPaola 2015). Phase I – II clinical trials of PROSTVAC in combination with other anti-cancer agent, are ongoing as of early 2018. Results of these trials will help establish the utility of PROSTVAC for treating prostate cancer (Madan 2017; Fong 2017; Gulley 2017). Several other vaccine approaches are also currently being tested in earlier stage clinical trials (Lilleby 2017; Heery 2016; Yoshimura 2016).

Checkpoint inhibitors are another class of immunotherapy agents. These drugs were developed in response to the discovery of immune checkpoint proteins, which tumor cells engage to deactivate immune cells (Azoury 2015; Dyck 2017). Checkpoint inhibitors interfere with this process, allowing the patient’s immune system to continue fighting the tumor (Rijnders 2017; Madan, Gulley 2017; Popovic 2017). In a small study testing the checkpoint inhibitor pembrolizumab (Keytruda) in patients with metastatic castration-resistant prostate cancer, three of 10 patients experienced rapid and dramatic PSA level reductions (Graff 2016). Similarly remarkable responses to the checkpoint inhibitors nivolumab (Opdivo) and ipilimumab (Yervoy) have been described in case reports (Basnet 2017; Cabel 2017). Additional clinical trials will help determine which patients are most likely to benefit from checkpoint-inhibitor immunotherapy (Popovic 2017).

Chimeric antigen receptor (CAR)-modified T-cell immunotherapy involves taking the patient’s T cells, genetically engineering the T cells to produce receptors that direct them to the cancer cells, and returning these CAR T cells to the patient’s body (NCI 2017b). In a phase-I clinical trial, 50% and 70% reductions in PSA levels were seen in two of five patients treated with CAR T-cell therapy (Junghans 2016). Promising results from animal models of prostate cancer using CAR T-cell therapy provide a foundation for further investigation (Kloss 2013; Gade 2005; Ma 2014; Zuccolotto 2014).

More information is available in the Cancer Immunotherapy protocol.

Screening, Diagnostic, and Prognostic Tests

Many men with slightly or moderately high PSA levels do not have cancer detected in their biopsy or do not have an aggressive form that needs treatment (Thompson 2004; Saini 2016). Several new tests are being developed to help men with moderate PSA level elevations decide whether to have a biopsy (Dani 2017; Carlsson 2017). A composite test called 4Kscore uses measurements of four different proteins in the blood along with clinical information about the patient to predict the likelihood that the cancer will spread within the next 15–20 years (Punnen 2015; Zappala 2017; Stattin 2015). A meta-analysis of published data concluded that the diagnostic accuracy of this test is similar to that of the FDA-approved Prostate Health Index (Russo 2017).

Genetic markers from cells in urine collected after a digital rectal exam may be useful predictors of cancer aggressiveness (Martignano 2017). In a trial with 1,077 participants, combined measurement of the gene markers TMPRSS2:ERG and PCA3 improved the ability to identify men at low risk for aggressive disease compared with PSA testing alone (Sanda 2017). Researchers examining genetic markers in urine samples from 905 participants with prostate cancer found two other markers (HOXC6 and DLX1 mRNA levels) that could help identify those with high-grade cancer (Van Neste 2016). These genetic tests could someday play a role in avoiding unnecessary biopsies (Martignano 2017).

New tests are also being developed to analyze tissue obtained through biopsy. The tissue may look healthy under a microscope, but certain molecular changes could indicate that a nearby cancer was missed by the biopsy needles. ConfirmMdx (Stewart 2013; Partin 2016) and the Prostate Core Mitomic Test (PCMT) (Robinson 2010; Legisi 2016) are two examples of commercially available tissue tests. Patients testing negative with these tests may opt for fewer or less frequent repeat biopsies (Wojno 2014; Legisi 2016).

Prostate tissue obtained through biopsy or surgery can be analyzed with new tests that may provide information on how aggressively the cancer should be treated:

  • Decipher has been assessed in over 2,000 patients and may predict the risk of metastasis (Nguyen 2017; Spratt 2017).
  • Oncotype DX Prostate Cancer Assay may provide information on tumor aggressiveness for men with clinically low-risk disease facing the choice between active surveillance or treatment (Brand 2016).
  • Prolaris and Promark may help prevent overtreatment by identifying men who are unlikely to benefit from more aggressive treatment (Cuzick 2015; Tosoian, Chappidi 2017; Koch 2016; Blume-Jensen 2015; Peabody 2017).

Although these tests are available and covered by Medicare for eligible patients, long-term and randomized trials are needed to confirm and compare their value (McMahon 2017; Metmark Genetics 2016).

Developments in imaging may improve diagnosis and assessment of prognosis. Positron emission tomography, or PET, provides information on how tissues and organs are functioning by measuring processes such as glucose metabolism and blood flow. PET scans use molecules called tracers that associate with cancers (Bednarova 2017). Researchers are working to understand how results from PET scans using various tracers can inform and improve treatment decisions (Dietlein 2017; Nanni 2016).

Repurposing Existing Drugs

Some drugs that are approved for the treatment of other diseases may be useful for treating prostate cancer. Much of the evidence supporting the potential benefits of these drugs comes from observational rather than clinical trials; however, several controlled trials are either underway or are being planned. The completion of such trials will help clarify whether there is a role for these repurposed drugs in prostate cancer treatment.

Statins are a category of cholesterol-lowering drugs. Among men with prostate cancer, those with high cholesterol levels are more likely to have high-grade and metastatic prostate cancer (Schnoeller 2017; Thysell 2010). In addition, men using statins to manage cholesterol have a lower risk of advanced prostate cancer and higher rate of prostate cancer survival (Alfaqih 2017). Several mechanisms by which statins may combat prostate cancer have been proposed, including modulation of cholesterol-signaling pathways in prostate tumors (cholesterol is the precursor to androgens, so statins may reduce androgen bioavailability in prostate cancer cells). Statins may also influence enzymes that participate in cell migration and tumor progression. Randomized controlled trials are needed to determine whether adding statins to prostate cancer treatment leads to better outcomes (Mucci 2017).

Preliminary data suggest aspirin may reduce prostate cancer recurrence (Smith 2017), prostate cancer-related death (Jacobs 2014), or death from any cause (Zhou 2017). The ADD-ASPIRIN trial is recruiting over 2,000 patients with prostate cancer to further test whether aspirin can prevent cancer recurrence (Coyle 2016).

The diabetes drug metformin may slow prostate cancer growth (Whitburn 2017; Sarmento-Cabral 2017). Metformin has been shown to enhance the ability of hormone therapy and radiation therapy to destroy prostate cancer cells in the lab and prostate tumors in mice (Colquhoun 2012; Whitburn 2017; Zhang 2014; Liu 2017). In one study in 44 men with metastatic prostate cancer, metformin (1,000 mg twice daily) stabilized the disease and extended PSA doubling time in a significant number of participants (Rothermundt 2014). A systematic review and meta-analysis of 30 cohort studies, including over 1.6 million prostate cancer patients, found that those who were taking metformin had improved overall survival, prostate cancer-specific survival, and recurrence-free survival compared with those who were not taking metformin. However, metformin use did not decrease the incidence of prostate cancer (He 2019). On the other hand, metformin use had no effect on survival outcomes in three recent studies examining patients with castration-resistant prostate cancer being treated with enzalutamide (Joshua 2022). Randomized controlled trials are ongoing to determine metformin’s potential role in treating prostate cancer (NLM 2023).

8 Dietary and Lifestyle Considerations

In addition to the information presented here, readers should also review the Prostate Cancer Prevention protocol, as it contains additional information about the potential role of diet and lifestyle factors in preventing prostate cancer.

Exercise and Body Weight

Regular exercise and maintaining a healthy body weight has been associated with better outcomes and quality of life for prostate cancer patients (Peisch 2017). A higher body mass index (BMI) has been associated with increased risk of aggressive prostate cancer (Xie, Zhang 2017). In one large observational trial, 5,158 men with prostate cancer were followed for several decades. In this study, long-term weight gain of more than 30 pounds was associated with a roughly 60% increased risk of prostate cancer-related death among non-smokers (Dickerman 2017; Perez-Cornago, Appleby 2017).

A meta-analysis of data on 1,199 participants from 32 clinical trials concluded that resistance exercise counters losses of muscle mass and strength associated with prostate cancer and its treatments (Keilani 2017). Another meta-analysis, which combined data from 1,574 participants in 16 randomized controlled trials, found exercise improved quality of life and reduced fatigue caused by prostate cancer (Bourke 2016). In one study with 25 patients, improved fitness was associated with slower rises in PSA levels (Hvid 2016). Additional studies are needed to address whether exercise programs can slow disease progression and improve survival (Hart 2017).

Exercise may be particularly helpful for patients on hormone therapy. Meta-analyses have shown that exercise improves some of the negative side effects attributed to hormone therapy, including muscle weakness, fatigue, weight gain, and sexual dysfunction (Yunfeng 2017; Baguley 2017). Results from one study suggest that, among patients on hormone therapy, those with the highest levels of fatigue may be the most likely to benefit from starting an exercise program (Taaffe 2017).


Emerging evidence suggests a diet emphasizing fruits, vegetables, and whole grains may contribute to reduced prostate cancer risk and improved prognosis and quality of life in prostate cancer patients (Carmody 2008; Nguyen 2006; Saxe 2001). In addition, preliminary evidence suggests specific foods, such as tomato sauce, cruciferous vegetables, olive oil, nuts, fish, and coffee, may be associated with lower risk of prostate cancer progression (Peisch 2017).

The Mediterranean diet is high in cancer-fighting phytonutrients, mainly from fruits, vegetables, whole grains, and olive oil, and has been associated with reduced risk of prostate cancer and prostate cancer-related death (Capurso 2017). In one study, men in the highest 25% of intake of cruciferous vegetables, such as broccoli, cabbage, and cauliflower, had about 60% reduced risk of prostate cancer progression compared with men whose intake was in the lowest 25% of the distribution (Richman 2012; Kirsh 2007). An association between higher fruit and vegetable consumption in general and increased prostate cancer survival has also been noted (Taborelli 2017).

Saturated fats, meat, and dairy may contribute to the development and progression of prostate cancer (Peisch 2017). One study noted that Swedish men with localized prostate cancer whose daily diet included at least three servings of high-fat milk were six times more likely to die of the disease; those reporting low-fat milk intake showed an associated borderline reduction in prostate cancer death (Downer 2017). Reducing saturated fat and increasing fruit and vegetable intake has been observed to prevent PSA level increases in men previously treated for prostate cancer (Hebert 2012).

Eating more fruits and vegetables and less red meat and saturated fat may also reduce prostate cancer risk and improve outcomes for some men with prostate cancer (Ballon-Landa 2018; Wilson 2016). Processed red meat and red meat cooked at high temperatures may be especially problematic and should be minimized (Wilson 2016).

A low ratio of omega-6 to omega-3 fatty acids in the diet may benefit prostate cancer patients (Apte 2013; Aronson 2011). In a group of 525 Swedish men with prostate cancer, the 25% of participants with the highest intake of the omega-3 fatty acid docosahexaenoic acid (DHA) and total marine fatty acids were 40% less likely to die of prostate cancer (Epstein 2012).

Carotenoids are plant pigments with documented health benefits, including some anti-cancer properties (Aghajanpour 2017). In one study, low circulating carotenoid levels were associated with more high-grade prostate cancers (Nordstrom 2016). In a study in men with recurrent prostate cancer participating in a 6-month program to improve diet and lifestyle, those with higher blood levels of carotenoids, including lycopene (a red pigment found in foods like tomatoes), had lower PSA levels at the end of the study (Antwi 2015). Cooked tomatoes are an especially rich source of lycopene (Story 2010). Higher consumption of lycopene has been correlated with a lower rate of prostate cancer diagnosis, especially lethal cancer (Chen 2013; Zu 2014).

Several population studies have shown that drinking coffee is associated with reduced risk of prostate cancer, especially lethal prostate cancer (Wang 2016; Pounis 2017; Wilson 2011; Peisch 2017). In a study of 630 men diagnosed with prostate cancer, those who drank an average of four cups of coffee per day or more had a 59% lower risk of cancer recurrence than those who drank one cup per day or less (Geybels 2013).


Smoking may be particularly harmful for men diagnosed with prostate cancer (Peisch 2017). Smokers are more likely to be diagnosed with aggressive disease and 61% more likely to die from the disease as compared to never smokers (Kenfield 2011). In a study of over 2,000 men, those who were smokers at the time of radiation therapy were more than twice as likely to die from their disease (Steinberger 2015). Other studies have found that smokers treated with radical prostatectomy were more likely to have rising PSA levels after treatment (Rieken 2015) and die earlier than non-smokers (Curtis 2017). Smokers have also been found to be more likely to experience treatment-related fatigue during chemotherapy with docetaxel (Bergin 2017) and complications after prostatectomy (Byun 2017).

9 Nutrients

Vitamin D

In laboratory studies, vitamin D interferes with several cancer processes (Pdq Integrative 2017; Abu El Maaty 2017; Moukayed 2017). For instance, laboratory data suggest vitamin D can prevent cancer cells from metastasizing (Hsu 2011). Several animal studies have shown that under some conditions vitamin D can control tumor growth (Pdq Integrative 2017; Mordan-McCombs 2010; Ajibade 2014). In addition, vitamin D can boost the immune system, possibly helping it identify and destroy cancer cells (Pandolfi 2017).

Several studies have explored whether vitamin D can help fight prostate cancer in humans (Brandstedt 2016; Xie, Chen 2017). In one study, serum vitamin D levels were analyzed before diagnosis in 1,000 patients with prostate cancer. Those with higher vitamin D levels were significantly less likely to die from the disease (Mondul 2016). In another study, short-term supplementation with high-dose vitamin D for three to eight weeks lowered PSA levels (Wagner 2013). As part of another study, 52 men with low-risk prostate cancer being monitored with active surveillance took 4,000 IU vitamin D3 daily for one year. In 55% of the men, the prostate cancer was less extensive at the end of the study than at the beginning based on biopsy analysis (Marshall 2012). Vitamin D supplementation improved PSA test results in two additional studies (Srinivas 2009; Newsom-Davis 2009).

Hormone therapy can weaken the bones of prostate cancer patients, but supplemental vitamin D may help prevent fractures in these patients (Ottanelli 2015; Dueregger 2014). A study examining factors associated with bone preservation in prostate cancer patients using hormone therapies found that those taking vitamin D supplements experienced less bone loss in their lower-back vertebrae (Alibhai 2013).

Green Tea

Green tea and its catechins, including epigallocatechin gallate or EGCG, may be helpful in fighting prostate cancer. In laboratory studies, EGCG slowed prostate tumor growth and caused cancer cells to die (Li 2014; Lin 2015). EGCG may also interfere with hormone signaling in prostate cancer cells (Ren 2000; Siddiqui 2011; Lee 2012).

Several human trials have suggested green tea and its catechins can prevent prostate cancer, particularly in men with high-grade prostatic intraepithelial neoplasia, or PIN, a precancerous condition (Pdq Integrative 2017; Jacob 2017). In a placebo-controlled trial, PSA levels decreased in men diagnosed with high-grade PIN taking 400 mg EGCG daily (Kumar 2015); furthermore, no toxic effects were seen after one year of EGCG supplementation at this dose (Kumar 2016). In a meta-analysis of multiple studies in men with high-grade PIN, taking green tea catechins reduced the rate of progression to prostate cancer from 23.1% to 7.6% (Cui 2017).

In a randomized trial, 113 men diagnosed with prostate cancer were assigned to drink six cups per day of green tea, black tea, or water for at least three weeks prior to prostatectomy. PSA levels significantly decreased in the group taking green tea (Henning 2015). In another trial, taking a green tea catechin supplement providing 800 mg EGCG daily was found to decrease levels of PSA and some other cancer markers in the blood in men with biopsy-confirmed prostate cancer awaiting prostatectomy (McLarty 2009).

Fish Oil and Omega-3 Fatty Acids

Oily fish are high in omega-3 polyunsaturated fatty acids (Ruxton 2004). These fatty acids have many health benefits and may even slow the growth of prostate cancer (Li 2014; Berquin 2011; Aucoin 2017). In laboratory and animal studies, omega-3 fatty acids were found to inhibit inflammation, interfere with blood vessel growth in tumors, and cause cancer cells to die (Spencer 2009; Gu 2013). Mice with prostate cancer whose only source of fat was fish oil survived longer than control mice fed diets with olive oil, corn oil, or animal fat (Lloyd 2013). Further analysis found that omega-3 fatty acids had beneficial effects on several types of cancer-fighting immune cells in the mice (Liang 2016). 

In a study that included more than 290,000 men, those who reported high fish and high omega-3 fatty acid intake on diet questionnaires at the beginning of the study were significantly less likely to die from prostate cancer during approximately 20 years of follow up (Bosire 2013). In a randomized trial, men scheduled for radical prostatectomy ate either a low-fat diet supplemented with 5 grams of fish oil daily or a traditional Western diet. Prostate cancer cells exposed to blood taken from the men eating the low-fat plus fish oil diet showed decreased growth in the laboratory (Aronson 2011). A second analysis of this same study found that pro-inflammatory marker levels were decreased and scores on a prognostic test were more favorable in the patients eating the low-fat plus fish oil diet (Galet 2014). In a study in men with low-risk prostate cancer undergoing active surveillance, higher tumor levels of omega-3 fatty acids, particularly the marine omega-3 fatty acid eicosapentaenoic acid (EPA), were associated with reduced risk of prostate cancer progression (Moreel 2014).

Flaxseed is a plant source of omega-3 fatty acids and fiber, as well as a class of polyphenols called lignans that have weak estrogenic activity (Kajla 2015). In one study, 25 men awaiting surgery for prostate cancer ate a low-fat diet supplemented with 30 grams of ground flaxseeds per day. Several tests indicated that the diet may have reduced cancer cell survival and proliferation (Demark-Wahnefried 2001). In a larger follow-up study, a similar group of patients ate either 30 grams ground flaxseeds per day, a low-fat diet, a low-fat diet plus 30 grams ground flaxseeds per day, or a control diet. Flaxseed supplementation, even without the context of a low-fat diet, was associated with molecular changes that may indicate that cancer cells were dividing more slowly (Demark-Wahnefried 2008).


As described in the “Dietary and Lifestyle Considerations” section, lycopene may help reduce risks of prostate cancer. Beneficial cancer-fighting effects of lycopene have been demonstrated in laboratory studies (Pdq Integrative 2017; Lin 2015). Small clinical studies in humans have shown that supplemental lycopene is safe and may reduce prostate cancer cell activity (Pdq Integrative 2017; Kumar 2008).

In a randomized controlled trial, men being treated with surgical removal of the testicles had a more consistent decrease in PSA levels if they were taking 4 mg per day of supplemental lycopene (Ansari 2003). Another randomized trial found that taking 30 mg lycopene per day reduced levels of markers of tumor growth in men newly diagnosed with localized prostate cancer (Kucuk 2001). In addition, men with intermediate-risk prostate cancer who ate tomato products providing 30 mg lycopene daily had significant decreases in PSA levels after three weeks (Paur 2017).


Pomegranate contains a number of compounds that combat free radicals, and extracts from pomegranate interfere with cancer cell division in laboratory research (Pdq Integrative 2017). In a study designed to simulate consumption of one to two pomegranate fruits per day in an average adult human, mice injected with prostate cancer cells drank either plain water or water with pomegranate extract. Tumor onset was later and tumor growth was slower in the mice receiving the pomegranate extract (Malik 2005). In a study using experimental mice bred to be highly susceptible to prostate cancer, the same dose of pomegranate extract prevented metastasis and increased survival (Adhami 2012). Several other animal studies have shown similar results (Seeram 2007; Sartippour 2008; Albrecht 2004).

Pomegranate products have also been tested in human studies. In one trial, the average PSA doubling time increased from 15 months to 54 months in men with rising PSA levels after surgery or radiation therapy who drank eight ounces of pomegranate juice daily. Prostate cancer cells exposed to blood taken from patients treated in this study did not divide as rapidly and were more likely to die (Pantuck 2006). A randomized trial in a similar patient population found that doses of 1 and 3 grams of pomegranate extract per day extended PSA doubling time by 58% and 43%, respectively, an effect that was statistically the same for the two doses (Paller 2013).

Cruciferous Vegetable Isothiocyanates

Cruciferous vegetables such as cabbage, broccoli, cauliflower, collard greens, arugula, Brussels sprouts, and kale contain phytochemicals called glucosinolates. During food preparation, chewing, and digestion, glucosinolates are broken down into isothiocyanatets (eg, sulforaphane) and other bioactive compounds called indoles (eg, indole-3-carbinol). The cruciferous-vegetable-breakdown products have some compelling anti-prostate-cancer properties (Novio 2016; Watson 2013). Epidemiological studies have found correlations between greater intake of cruciferous vegetables and reduced risk of prostate cancer (Watson 2013). A small clinical study in which 20 men with prostate cancer took an isothiocyanate-rich broccoli extract for up to 20 weeks showed that PSA doubling time increased during treatment (Alumkal 2015). A meta-analysis of observational studies found that cruciferous vegetable consumption was associated with a roughly 20% relative prostate cancer risk reduction among men who ate the most cruciferous vegetables versus those who ate the least (Liu 2012). As of the time of this writing in early 2018, four clinical trials examining different cruciferous vegetable derivatives or preparations are pending publication of results.


Cranberries are a rich source of phytonutrients known to boost the immune system and fight infection, and laboratory and clinical data suggest cranberry products may be useful for cancer patients (Weh 2016). In several laboratory studies, various preparations of cranberry juice have been shown to interfere with cancer cell division and signals that boost cancer growth (Weh 2016; Deziel 2012; Deziel 2010). In an animal model of prostate cancer, a purified proanthocyanidin-rich extract from cranberries significantly slowed prostate tumor growth (Ferguson 2006).

In a controlled clinical trial, 64 participants scheduled for radical prostatectomy took either 1,500 mg per day of cranberry fruit powder or placebo for at least 21 days prior to surgery. Average PSA levels decreased by 22.5% in the group taking cranberry and increased by 0.9% in the placebo group (Student 2016).

Some studies have addressed whether cranberry can help relieve urinary symptoms in men treated for prostate cancer. Urinary tract infections are a common side effect of radiation therapy (Flannigan 2014; Bonetta 2012). Cranberry extract can interfere with the ability of bacteria to stick to tissue in the urinary tract (Weh 2016; Sobota 1984; Hisano 2012). In a randomized controlled trial in 370 men undergoing radiation therapy, those receiving 200 mg cranberry extract daily had a lower rate of urinary tract infections than those receiving placebo (8.7% vs. 24.2%) (Bonetta 2012). A large follow-up study confirmed these results in a group of 924 participants (Bonetta 2017). In a separate study, cranberry extracts protected men being treated with radiation therapy from another common side effect—inflammation of the bladder (Hamilton 2015).


Soy isoflavones such as genistein have been studied extensively for their anti-inflammatory and estrogen-modulating effects (Danciu 2017). Laboratory data on prostate cancer cells suggest isoflavones may reduce inflammation and interfere with signals that promote blood vessel growth in tumors (Swami 2009; Rabiau 2010). Genistein has been shown to slow prostate tumor cell proliferation in laboratory and animal models (Ajdzanovic 2013; Wang 2004; El Touny 2009). Findings from other studies suggest isoflavones may make prostate cancer cells more sensitive to radiation therapy (Raffoul 2007; Singh-Gupta 2010).

In a randomized controlled trial, 32 patients with rising PSA levels after prostate cancer treatment added two slices of soy-enriched bread, providing 34 mg of isoflavones per slice, or a placebo bread to their daily diet. Reduced levels of markers of inflammation and suppressed cancer-promoting immune activity were seen in those receiving isoflavones in their bread (Lesinski 2015). In another randomized trial including 54 patients scheduled for prostatectomy, those who received 30 mg genistein per day had a 7.8% drop in PSA levels versus a 4.4% increase in the placebo group (Lazarevic 2011). Two small open trials using isoflavone-containing soy beverages noted reductions in PSA level increases in participants with rising post-treatment PSA levels (Kwan 2010; Pendleton 2008).

Some clinical trials have found that isoflavones do not affect PSA levels or other health parameters (deVere White 2010; Hamilton-Reeves 2013). Inconsistencies in preparations, doses, participant characteristics, and treatment durations make it difficult to draw conclusions. Future research into the effects of soy and isoflavones on prostate cancer outcomes is needed.

Modified Citrus Pectin

Pectin is an indigestible carbohydrate that is especially abundant in the peels and pulp of citrus fruits. Modified citrus pectin (MCP) is pectin that has been chemically modified to break into smaller carbohydrate chains that can be absorbed into the blood. Studies have shown that these small bits of MCP inhibit a molecule called galectin-3. Cancer cells use galectin-3 during metastasis, and inhibiting galectin-3 may impede cancer cells’ ability to spread (Leclere 2013; Zhang 2018; Jiang 2013).

Indeed, findings from a study using a rat model of prostate cancer suggest oral MCP may reduce metastases. Although nearly all untreated rats had metastases after 30 days, only about half of the rats drinking water containing MCP had metastases (Pienta 1995).

In a small clinical trial, 10 men with rising PSA levels after treatment for prostate cancer received 14.4 grams per day of MCP for 12 months; PSA doubling times increased in seven of the 10 men (Guess 2003). Another open trial tested the effects of MCP supplementation, at 15 grams per day, in participants with a variety of advanced solid cancers. MCP led to improved quality of life and disease stabilization in 20.7% of the 29 participants who completed eight weeks of supplementation. One participant with metastatic prostate cancer had a remarkable response, with a 50% decreased PSA level, improved quality of life, and decreased pain at 16 weeks (Azémar 2007). An ongoing clinical trial is evaluating the effect of MCP, at a dose of 4.8 grams three times per day, on PSA levels (Keizman 2017).

Laboratory research suggests MCP may prevent tumor growth and spread by interfering with cell-cell interaction and adherence (Leclere 2013). MCP and a similar product called fractionated pectin powder have also been shown to cause cell death in prostate cancer cell cultures (Jackson 2007; Yan 2010).


Curcumin, a carotenoid pigment extracted from the spice turmeric, has well-established anti-inflammatory and oxidative stress-reducing effects. In laboratory studies, curcumin interfered with cancer growth signals, decreased androgen receptor activity, reduced production of PSA, and slowed tumor growth (Li 2014; Lin 2015; Goel 2010; Rivera 2017). In one trial, 36 patients with castration-resistant prostate cancer and rising PSA levels were given 6,000 mg curcumin per day while undergoing treatment with docetaxel and prednisone. Positive PSA responses were noted in 59% of participants (Mahammedi 2016). Another study with 85 participants found that a combination of curcumin and soy isoflavones markedly reduced PSA levels in men with high PSA levels and negative biopsies (Ide 2010).


Healthy prostate cells accumulate zinc to accomplish their normal cellular functions. In contrast, prostate cancer cells have depleted zinc stores, which makes them less susceptible to cell death (Costello 2016; Eidelman 2017; Franz 2013). When prostate cancer cells are treated with zinc in the laboratory, they begin to die (Feng 2002). In a group of over 35,000 men, those taking higher amounts of supplemental zinc were observed to be significantly less likely to be diagnosed with advanced prostate cancer (Gonzalez 2009). Another observational study in 525 men noted that those with higher dietary zinc intake around the time of their prostate cancer diagnosis had a lower risk of dying from prostate cancer (Epstein 2011).


Melatonin, a hormone best known for its role in regulating sleep, is also emerging as a promising anti-cancer agent. Evidence to date has shown that melatonin can interfere with cancer initiation, progression, and metastasis (Reiter 2017). In an observational study, men with higher levels of melatonin metabolites in their urine were found to be significantly less likely to have prostate cancer, especially advanced prostate cancer (Tai 2016). When rodents with prostate cancer were treated with supplemental melatonin, blood vessel growth was inhibited and the tumors grew more slowly (Paroni 2014; Xi 2001; Siu 2002; Mayo 2017). Melatonin may fight prostate cancer by interfering with androgen receptor signaling (Reiter 2017). Melatonin has also been shown to decrease glucose metabolism in prostate cancer cells, reducing cancer cells’ ATP production (ATP is a key cellular-energy-storage compound) (Hevia 2017). Melatonin may also enhance cancer cells’ sensitivity to conventional anti-cancer drugs, possibly complementing standard therapy (Reiter 2017).

Milk Thistle and Silymarin

Milk thistle (Silybum marianum) has been used for thousands of years as an herbal remedy for liver disorders. One of the main active ingredients in the seeds and fruit of milk thistle is a flavonoid complex called silymarin (Vue 2016; Abenavoli 2010; Vaknin 2008). Many studies have tested the effects of silymarin on rodents with prostate cancer and on prostate cancer cells in the laboratory. For example, one component of silymarin, called silibinin, reduced the creation of new blood vessels in tumors and slowed tumor growth in mice with prostate cancer (Deep 2017). In another study, silibinin made prostate tumors in mice more sensitive to the effects of radiation yet protected healthy tissues from radiation damage (Nambiar 2015).

Silibinin is being tested in clinical trials for breast cancer (Lazzeroni 2016), hepatitis C infection (Braun 2015), and liver cancer (Siegel 2014). In six patients with prostate cancer awaiting prostatectomy, taking 13 grams daily of a preparation of silibinin led to high levels of silibinin in the blood; however, levels were very low in the prostate tissue obtained during surgery (Flaig 2010). Recent studies have explored variations in the silibinin compound that may be more potent and may reach the prostate tissue more effectively (Vue 2017; Manivannan 2017).


  • Mar: Updated section on testosterone replacement therapy and prostate cancer in Conventional Treatment


  • Jul: Updated discussion of metformin in Repurposing Existing Drugs


  • Sep: Added section on locating an experienced prostate cancer physician to Conventional Treatment
  • Mar: Updated section on improvements to conventional treatments in Novel and Emerging Strategies
  • Mar: Updated section on hormone therapy in Conventional Treatment
  • Mar: Added section on bone loss and prostate cancer to Conventional Treatment


  • Nov: Updated Conventional Treatment section


  • Feb: Comprehensive update & review

Disclaimer and Safety Information

This information (and any accompanying material) is not intended to replace the attention or advice of a physician or other qualified health care professional. Anyone who wishes to embark on any dietary, drug, exercise, or other lifestyle change intended to prevent or treat a specific disease or condition should first consult with and seek clearance from a physician or other qualified health care professional. Pregnant women in particular should seek the advice of a physician before using any protocol listed on this website. The protocols described on this website are for adults only, unless otherwise specified. Product labels may contain important safety information and the most recent product information provided by the product manufacturers should be carefully reviewed prior to use to verify the dose, administration, and contraindications. National, state, and local laws may vary regarding the use and application of many of the therapies discussed. The reader assumes the risk of any injuries. The authors and publishers, their affiliates and assigns are not liable for any injury and/or damage to persons arising from this protocol and expressly disclaim responsibility for any adverse effects resulting from the use of the information contained herein.

The protocols raise many issues that are subject to change as new data emerge. None of our suggested protocol regimens can guarantee health benefits. Life Extension has not performed independent verification of the data contained in the referenced materials, and expressly disclaims responsibility for any error in the literature.


Abbas TO, Al-Naimi AR, Yakoob RA, Al-Bozom IA, Alobaidly AM. Prostate cancer metastases to the rectum: a case report. World journal of surgical oncology.May 21 2011;9:56.

Abenavoli L, Capasso R, Milic N, Capasso F. Milk thistle in liver diseases: past, present, future. Phytotherapy research: PTR.Oct 2010;24(10):1423-1432.

Abu El Maaty MA, Wolfl S. Vitamin D as a Novel Regulator of Tumor Metabolism: Insights on Potential Mechanisms and Implications for Anti-Cancer Therapy. International journal of molecular sciences. Oct 19 2017;18(10).

ACS. American Cancer Society. Chemmotherapy for prostate cancer. Available at last updated 03/11/2016. Accessed 12/08/2017.

ACS. American Cancer Society. Understanding Your Pathology Report: Prostate Cancer. Last updated 3/8/2017. Accessed 11/29/2017.

Adhami VM, Siddiqui IA, Syed DN, Lall RK, Mukhtar H. Oral infusion of pomegranate fruit extract inhibits prostate carcinogenesis in the TRAMP model. Carcinogenesis.Mar 2012;33(3):644-651.

Adhyam M, Gupta AK. A Review on the Clinical Utility of PSA in Cancer Prostate. Indian journal of surgical oncology.Jun 2012;3(2):120-129.

Aghajanpour M, Nazer MR, Obeidavi Z, Akbari M, Ezati P, Kor NM. Functional foods and their role in cancer prevention and health promotion: a comprehensive review. American journal of cancer research.2017;7(4):740-769.

Ahmed HU, El-Shater Bosaily A, Brown LC, Gabe R, Kaplan R, Parmar MK, . . . Emberton M. Diagnostic accuracy of multi-parametric MRI and TRUS biopsy in prostate cancer (PROMIS): a paired validating confirmatory study. Lancet.Feb 25 2017;389(10071):815-822.

Ajdzanovic V, Mojic M, Maksimovic-Ivanic D, Bulatovic M, Mijatovic S, Milosevic V, Spasojevic I. Membrane fluidity, invasiveness and dynamic phenotype of metastatic prostate cancer cells after treatment with soy isoflavones. The Journal of membrane biology.Apr 2013;246(4):307-314.

Ajibade AA, Kirk JS, Karasik E, Gillard B, Moser MT, Johnson CS, . . . Foster BA. Early growth inhibition is followed by increased metastatic disease with vitamin D (calcitriol) treatment in the TRAMP model of prostate cancer. PloS one.2014;9(2):e89555.

Albala D, Kemeter MJ, Febbo PG, Lu R, John V, Stoy D, . . . Dubeck F. Health Economic Impact and Prospective Clinical Utility of Oncotype DX(R) Genomic Prostate Score. Rev Urol.2016;18(3):123-132.

Albisinni S, Aoun F, Bellucci S, Biaou I, Limani K, Hawaux E, . . . van Velthoven R. Comparing High-Intensity Focal Ultrasound Hemiablation to Robotic Radical Prostatectomy in the Management of Unilateral Prostate Cancer: A Matched-Pair Analysis. Journal of endourology / Endourological Society. Jan 2017;31(1):14-19.

Albrecht M, Jiang W, Kumi-Diaka J, Lansky EP, Gommersall LM, Patel A, . . . Campbell MJ. Pomegranate extracts potently suppress proliferation, xenograft growth, and invasion of human prostate cancer cells. Journal of medicinal food.Fall 2004;7(3):274-283.

Alfaqih MA, Allott EH, Hamilton RJ, Freeman MR, Freedland SJ. The current evidence on statin use and prostate cancer prevention: are we there yet? Nature reviews. Urology. Feb 2017;14(2):107-119.

Alibhai SM, Mohamedali HZ, Gulamhusein H, Panju AH, Breunis H, Timilshina N, . . . Cheung AM. Changes in bone mineral density in men starting androgen deprivation therapy and the protective role of vitamin D. Osteoporosis international: a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA.Oct 2013;24(10):2571-2579.

Alumkal JJ, Slottke R, Schwartzman J, Cherala G, Munar M, Graff JN, . . . Mori M. A phase II study of sulforaphane-rich broccoli sprout extracts in men with recurrent prostate cancer. Investigational new drugs.Apr 2015;33(2):480-489.

Andriole GL, Crawford ED, Grubb RL, 3rd, Buys SS, Chia D, Church TR, . . . Prorok PC. Prostate cancer screening in the randomized Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial: mortality results after 13 years of follow-up. J Natl Cancer Inst.Jan 18 2012;104(2):125-132.

Ansari MS, Gupta NP. A comparison of lycopene and orchidectomy vs orchidectomy alone in the management of advanced prostate cancer. BJU Int.Sep 2003;92(4):375-378; discussion 378.

Antonarakis ES, Kibel AS, Yu EY, Karsh LI, Elfiky A, Shore ND, . . . Drake CG. Sequencing of Sipuleucel-T and Androgen Deprivation Therapy in Men with Hormone-Sensitive Biochemically Recurrent Prostate Cancer: A Phase II Randomized Trial. Clinical cancer research: an official journal of the American Association for Cancer Research.May 15 2017;23(10):2451-2459.

Antwi SO, Steck SE, Zhang H, Stumm L, Zhang J, Hurley TG, Hebert JR. Plasma carotenoids and tocopherols in relation to prostate-specific antigen (PSA) levels among men with biochemical recurrence of prostate cancer. Cancer epidemiology.Oct 2015;39(5):752-762.

Apte SA, Cavazos DA, Whelan KA, Degraffenried LA. A low dietary ratio of omega-6 to omega-3 Fatty acids may delay progression of prostate cancer. Nutrition and cancer.2013;65(4):556-562.

Aronson WJ, Kobayashi N, Barnard RJ, Henning S, Huang M, Jardack PM, . . . Galet C. Phase II prospective randomized trial of a low-fat diet with fish oil supplementation in men undergoing radical prostatectomy. Cancer prevention research (Philadelphia, Pa.).Dec 2011;4(12):2062-2071.

Aucoin M, Cooley K, Knee C, Fritz H, Balneaves LG, Breau R, . . . Seely D. Fish-Derived Omega-3 Fatty Acids and Prostate Cancer: A Systematic Review. Integrative cancer therapies.Mar 2017;16(1):32-62.

Augmenix. What is SpaceOAR Hydrogel? Copyright by Augmenix, Inc. Accessed 12/28/2017.

Ayyildiz SN, Ayyildiz A. PSA, PSA derivatives, proPSA and prostate health index in the diagnosis of prostate cancer. Turkish journal of urology. Jun 2014;40(2):82-88.

Azémar M, Hildenbrand B, Haering B, Heim ME, Unger C. Clinical Benefit in Patients with Advanced Solid Tumors Treated with Modified Citrus Pectin: A Prospective Pilot Study. Clin Med Oncol. 2007;1:73-80.

Azoury SC, Straughan DM, Shukla V. Immune Checkpoint Inhibitors for Cancer Therapy: Clinical Efficacy and Safety. Current cancer drug targets.2015;15(6):452-462.

Azzouzi AR, Vincendeau S, Barret E, Cicco A, Kleinclauss F, van der Poel HG, . . . Emberton M. Padeliporfin vascular-targeted photodynamic therapy versus active surveillance in men with low-risk prostate cancer (CLIN1001 PCM301): an open-label, phase 3, randomised controlled trial. The Lancet. Oncology.Feb 2017;18(2):181-191.

Baade PD, Youlden DR, Gardiner RA, Ferguson M, Aitken JF, Yaxley J, Chambers SK. Factors associated with treatment received by men diagnosed with prostate cancer in Queensland, Australia. BJU Int. Dec 2012;110(11 Pt B):E712-719.

Bagheri MH, Ahlman MA, Lindenberg L, Turkbey B, Lin J, Cahid Civelek A, . . . Apolo AB. Advances in medical imaging for the diagnosis and management of common genitourinary cancers. Urologic oncology.Jul 2017;35(7):473-491.

Baguley BJ, Bolam KA, Wright ORL, Skinner TL. The Effect of Nutrition Therapy and Exercise on Cancer-Related Fatigue and Quality of Life in Men with Prostate Cancer: A Systematic Review. Nutrients.Sep 12 2017;9(9).

Bahn D, de Castro Abreu AL, Gill IS, Hung AJ, Silverman P, Gross ME, . . . Ukimura O. Focal cryotherapy for clinically unilateral, low-intermediate risk prostate cancer in 73 men with a median follow-up of 3.7 years. Eur Urol.Jul 2012;62(1):55-63.

Ballon-Landa E, Parsons JK. Nutrition, physical activity, and lifestyle factors in prostate cancer prevention. Current opinion in urology.Jan 2018;28(1):55-61.

Bambury RM, Rathkopf DE. Novel and next-generation androgen receptor-directed therapies for prostate cancer: Beyond abiraterone and enzalutamide. Urologic oncology.Aug 2016;34(8):348-355.

Barrington WE, Schenk JM, Etzioni R, Arnold KB, Neuhouser ML, Thompson IM, Jr., . . . Kristal AR. Difference in Association of Obesity With Prostate Cancer Risk Between US African American and Non-Hispanic White Men in the Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA Oncol.Jun 2015;1(3):342-349.

Basnet A, Khullar G, Mehta R, Chittoria N. A Case of Locally Advanced Castration-resistant Prostate Cancer With Remarkable Response to Nivolumab. Clinical genitourinary cancer.Oct 2017;15(5):e881-e884.

Baum RP, Kulkami HR, Schuchardt C, Singh A, Wirtz M, Wiessalla S, Schottelius M, Mueller D, Klette I, Wester HJ. 177Lu-Labeled Prostate-Specific Membrane Antigen Radioligand Therapy of Metastatic Castration-Resistant Prostate Cancer: Safety and Efficacy. J Nucl Med.2016;57(7):1006-1013.

Bayer HealthCare Pharmaceuticals Inc. NUBEQA (darolutamide) Prescribing Information. Updated 1/2021. Accessed 3/23/2022,

Beauval JB, Cabarrou B, Gandaglia G, Patard PM, Ouzzane A, de la Taille A, . . . Roumiguie M. External validation of a nomogram for identification of pathologically favorable disease in intermediate risk prostate cancer patients. Prostate.Jun 2017;77(8):928-933.

Bednarova S, Lindenberg ML, Vinsensia M, Zuiani C, Choyke PL, Turkbey B. Positron emission tomography (PET) in primary prostate cancer staging and risk assessment. Transl Androl Urol. Jun 2017;6(3):413-423.

Bell MA, Campbell JD, Joice G, Sopko NA, Burnett AL. Shifting the Paradigm of Testosterone Replacement Therapy in Prostate Cancer. World J Mens Health. May 2018;36(2):103-109. doi:10.5534/wjmh.170007.

Bergin ART, Hovey E, Lloyd A, Marx G, Parente P, Rapke T, de Souza P. Docetaxel-related fatigue in men with metastatic prostate cancer: a descriptive analysis. Supportive care in cancer: official journal of the Multinational Association of Supportive Care in Cancer.Sep 2017;25(9):2871-2879.

Berman NK, Honig S, Cronstein BN, Pillinger MH. The effects of caffeine on bone mineral density and fracture risk. Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. Jan 4 2022;doi:10.1007/s00198-021-05972-w

Berquin IM, Edwards IJ, Kridel SJ, Chen YQ. Polyunsaturated fatty acid metabolism in prostate cancer. Cancer metastasis reviews.Dec 2011;30(3-4):295-309.

Bhasin S, Institute D-FC. Improving Quality of Life of Prostate Cancer Survivors With Androgen Deficiency. identifier: NCT03716739. Updated 1/19/2024. Accessed 3/25/2024.

Bhasin S, Travison TG, Pencina KM, et al. Prostate Safety Events During Testosterone Replacement Therapy in Men With Hypogonadism: A Randomized Clinical Trial. JAMA Netw Open. Dec 1 2023;6(12):e2348692. doi:10.1001/jamanetworkopen.2023.48692.

Bhindi B, Karnes RJ, Rangel LJ, Mason RJ, Gettman MT, Frank I, . . . Boorjian SA. Independent Validation of the American Joint Committee on Cancer 8th Edition Prostate Cancer Staging Classification. J Urol.Jun 29 2017.

Bibbins-Domingo K, Grossman DC, Curry SJ. The US Preventive Services Task Force 2017 Draft Recommendation Statement on Screening for Prostate Cancer: An Invitation to Review and Comment. JAMA.May 16 2017;317(19):1949-1950.

Bilusic M, Madan RA, Gulley JL. Immunotherapy of Prostate Cancer: Facts and Hopes. Clinical cancer research: an official journal of the American Association for Cancer Research.Jun 29 2017.

Bjurlin MA, Rosenkrantz AB, Taneja SS. MRI-fusion biopsy: the contemporary experience. Transl Androl Urol. Jun 2017;6(3):483-489.

Bjurlin MA, Wysock JS, Taneja SS. Optimization of prostate biopsy: review of technique and complications. The Urologic clinics of North America.May 2014;41(2):299-313.

Blume-Jensen P, Berman DM, Rimm DL, Shipitsin M, Putzi M, Nifong TP, . . . Saad F. Development and clinical validation of an in situ biopsy-based multimarker assay for risk stratification in prostate cancer. Clinical cancer research: an official journal of the American Association for Cancer Research. Jun 01 2015;21(11):2591-2600.

Boegemann M, Stephan C, Cammann H, Vincendeau S, Houlgatte A, Jung K, . . . Semjonow A. The percentage of prostate-specific antigen (PSA) isoform [-2]proPSA and the Prostate Health Index improve the diagnostic accuracy for clinically relevant prostate cancer at initial and repeat biopsy compared with total PSA and percentage free PSA in men aged </=65 years. BJU Int.Jan 2016;117(1):72-79.

Bonetta A, Di Pierro F. Enteric-coated, highly standardized cranberry extract reduces risk of UTIs and urinary symptoms during radiotherapy for prostate carcinoma. Cancer management and research.2012;4:281-286.

Bonetta A, Roviello G, Generali D, Zanotti L, Cappelletti MR, Pacifico C, Di Pierro F. Enteric-coated and highly standardized cranberry extract reduces antibiotic and nonsteroidal anti-inflammatory drug use for urinary tract infections during radiotherapy for prostate carcinoma. Research and reports in urology.2017;9:65-69.

Bosire C, Stampfer MJ, Subar AF, Park Y, Kirkpatrick SI, Chiuve SE, . . . Reedy J. Index-based dietary patterns and the risk of prostate cancer in the NIH-AARP diet and health study. Am J Epidemiol.Mar 15 2013;177(6):504-513.

Bourke L, Smith D, Steed L, Hooper R, Carter A, Catto J, . . . Rosario DJ. Exercise for Men with Prostate Cancer: A Systematic Review and Meta-analysis. Eur Urol. Apr 2016;69(4):693-703.

Brand TC, Zhang N, Crager MR, Maddala T, Dee A, Sesterhenn IA, . . . Lawrence HJ. Patient-specific Meta-analysis of 2 Clinical Validation Studies to Predict Pathologic Outcomes in Prostate Cancer Using the 17-Gene Genomic Prostate Score. Urology.Mar 2016;89:69-75.

Brandstedt J, Almquist M, Manjer J, Malm J. Vitamin D, PTH, and calcium in relation to survival following prostate cancer. Cancer Causes Control.May 2016;27(5):669-677.

Brauer A, Grubert LS, Roll W, Schrader AJ, Schafers M, Bogemann M, Rahbar K. 177Lu-PSMA-617 radioligand therapy and outcome in patients with metastasized castration-resistant prostate cancer. European journal of nuclear medicine and molecular imaging.Sep 2017;44(10):1663-1670.

Braun DL, Rauch A, Aouri M, Durisch N, Eberhard N, Anagnostopoulos A, . . . Fehr J. A Lead-In with Silibinin Prior to Triple-Therapy Translates into Favorable Treatment Outcomes in Difficult-To-Treat HIV/Hepatitis C Coinfected Patients. PloS one.2015;10(7):e0133028.

Brawer MK. Assays for complexed prostate-specific antigen and other advances in the diagnosis of prostate cancer. Rev Urol.2003;5 Suppl 6:S10-16.

Brawer MK, Meyer GE, Letran JL, Bankson DD, Morris DL, Yeung KK, Allard WJ. Measurement of complexed PSA improves specificity for early detection of prostate cancer. Urology.Sep 1998;52(3):372-378.

Broderick JM. FDA Grants Apalutamide Priority Review for Nonmetastatic CRPC. 12/21/2017. Accessed 01/08/2018.

Bubendorf L, Schöpfer A, Wagner U, et al. Metastatic patterns of prostate cancer: An autopsy study of 1,589 patients. Human Pathology. 2000;31(5):578-583.

Burstein HJ, Krilov L, Aragon-Ching JB, Baxter NN, Chiorean EG, Chow WA, . . . Dizon DS. Clinical Cancer Advances 2017: Annual Report on Progress Against Cancer From the American Society of Clinical Oncology. Journal of clinical oncology: official journal of the American Society of Clinical Oncology. Apr 20 2017;35(12):1341-1367.

Byun DJ, Cohn MR, Patel SN, Donin NM, Sosnowski R, Bjurlin MA. The Effect of Smoking on 30-Day Complications Following Radical Prostatectomy. Clinical genitourinary cancer.Apr 2017;15(2):e249-e253.

Cabel L, Loir E, Gravis G, Lavaud P, Massard C, Albiges L, . . . Fizazi K. Long-term complete remission with Ipilimumab in metastatic castrate-resistant prostate cancer: case report of two patients. Journal for immunotherapy of cancer.2017;5:31.

Capurso C, Vendemiale G. The Mediterranean Diet Reduces the Risk and Mortality of the Prostate Cancer: A Narrative Review. Frontiers in nutrition. 2017;4:38.

Caras RJ, Sterbis JR. Prostate cancer nomograms: a review of their use in cancer detection and treatment. Current urology reports.Mar 2014;15(3):391.

Carlsson SV, Roobol MJ. Improving the evaluation and diagnosis of clinically significant prostate cancer in 2017. Current opinion in urology.May 2017;27(3):198-204.

Carmody J, Olendzki B, Reed G, Andersen V, Rosenzweig P. A dietary intervention for recurrent prostate cancer after definitive primary treatment: results of a randomized pilot trial. Urology.Dec 2008;72(6):1324-1328.

CDC. Centers for Disease Control and Prevention. Prostate Cancer Risk by Age. Last updated 12/15/2015. Accessed 8/19/2017.

CDC. Centers for Disease Control and Prevention. National Hospital Discharge Survey: 2010 table, Procedures by selected patient characteristics - Number by procedure category and age. 2010. Accessed 8/29/2017.

CDC. Centers for Disease Control and Prevention. Prostate Cancer Rates by Race and Ethnicity. Last updated 6/19/2017. Accessed 8/19/2017.

Chedrawe E, Sathe A, White J, Ory J, Ramasamy R. Testosterone Therapy in Advanced Prostate Cancer. Androg Clin Res Ther. 2022;3(1):180-186. doi:10.1089/andro.2021.0035.

Cheetham PJ, Katz AE. Diet and prostate cancer - a holistic approach to management. Archivos espanoles de urologia. Oct 2011;64(8):720-734.

Chen H, Na R, Packiam VT, Conran CA, Jiang D, Tao S, . . . Xu J. Reclassification of prostate cancer risk using sequentially identified SNPs: Results from the REDUCE trial. Prostate.Aug 2017;77(11):1179-1186.

Chen J, Song Y, Zhang L. Lycopene/tomato consumption and the risk of prostate cancer: a systematic review and meta-analysis of prospective studies. J Nutr Sci Vitaminol (Tokyo).2013;59(3):213-223.

Chen N, Zhou Q. The evolving Gleason grading system. Chinese journal of cancer research = Chung-kuo yen cheng yen chiu. Feb 2016;28(1):58-64.

Cheng HH, Pritchard CC, Montgomery B, Lin DW, Nelson PS. Prostate Cancer Screening in a New Era of Genetics. Clinical genitourinary cancer.May 31 2017.

Chi KN, Agarwal N, Bjartell A, et al. Apalutamide for Metastatic, Castration-Sensitive Prostate Cancer. The New England journal of medicine. Jul 4 2019;381(1):13-24. doi:10.1056/NEJMoa1903307

Christie DR, Sharpley CF, Bitsika V. Why do patients regret their prostate cancer treatment? A systematic review of regret after treatment for localized prostate cancer. Psycho-oncology.Sep 2015;24(9):1002-1011.

Chu FM, Sartor O, Gomella L, Rudo T, Somerville MC, Hereghty B, Manyak MJ. A randomised, double-blind study comparing the addition of bicalutamide with or without dutasteride to GnRH analogue therapy in men with non-metastatic castrate-resistant prostate cancer. European journal of cancer (Oxford, England: 1990).Aug 2015;51(12):1555-1569.

Cicione A, De Nunzio C, Tubaro A, Cantiello F, Manno S, Oliveira C, . . . Damiano R. Metabolic syndrome diagnosis and widespread high grade prostatic intraepithelial neoplasia significantly increase prostate cancer risk: results from a multicenter biopsy study. BMC cancer. Feb 04 2016;16:59.

Colquhoun AJ, Venier NA, Vandersluis AD, Besla R, Sugar LM, Kiss A, . . . Venkateswaran V. Metformin enhances the antiproliferative and apoptotic effect of bicalutamide in prostate cancer. Prostate Cancer Prostatic Dis.Dec 2012;15(4):346-352.

Costa WH, Jabboure GN, Cunha IW. Urological cancer related to familial syndromes. International braz j urol: official journal of the Brazilian Society of Urology.Mar-Apr 2017;43(2):192-201.

Costello LC, Franklin RB. A comprehensive review of the role of zinc in normal prostate function and metabolism; and its implications in prostate cancer. Archives of biochemistry and biophysics.Dec 01 2016;611:100-112.

Counago F, Sancho G, Catala V, Hernandez D, Recio M, Montemuino S, . . . Del Cerro E. Magnetic resonance imaging for prostate cancer before radical and salvage radiotherapy: What radiation oncologists need to know. World journal of clinical oncology.Aug 10 2017;8(4):305-319.

Coyle C, Cafferty FH, Rowley S, MacKenzie M, Berkman L, Gupta S, . . . Langley RE. ADD-ASPIRIN: A phase III, double-blind, placebo controlled, randomised trial assessing the effects of aspirin on disease recurrence and survival after primary therapy in common non-metastatic solid tumours. Contemporary clinical trials.Nov 2016;51:56-64.

Crawford ED, Twardowski PW, Concepcion RS, et al. The Impact of Late Luteinizing Hormone-Releasing Hormone Agonist Dosing on Testosterone Suppression in Patients with Prostate Cancer: An Analysis of United States Clinical Data. J Urol. 2020;203(4):743-750.

Crouzet S, Blana A, Murat FJ, Pasticier G, Brown SCW, Conti GN, . . . Ward JF. Salvage high-intensity focused ultrasound (HIFU) for locally recurrent prostate cancer after failed radiation therapy: Multi-institutional analysis of 418 patients. BJU Int.Jun 2017;119(6):896-904.

Cui K, Li X, Du Y, Tang X, Arai S, Geng Y, . . . Zhang T. Chemoprevention of prostate cancer in men with high-grade prostatic intraepithelial neoplasia (HGPIN): a systematic review and adjusted indirect treatment comparison. Oncotarget.May 30 2017;8(22):36674-36684.

Curtis A, Ondracek RP, Murekeyisoni C, Kauffman E, Mohler J, Marshall J. Tobacco use and outcome in radical prostatectomy patients. Cancer Med. Apr 2017;6(4):857-864.

Cuzick J, Stone S, Fisher G, Yang ZH, North BV, Berney DM, . . . Scardino P. Validation of an RNA cell cycle progression score for predicting death from prostate cancer in a conservatively managed needle biopsy cohort. British journal of cancer.Jul 28 2015;113(3):382-389.

Danciu C, Avram S, Pavel I, Ghiulai R, Dehelean C, Ersilia A, . . . Soica C. Main Isoflavones Found in Dietary Sources as Natural Anti-inflammatory Agents. Current drug targets.Nov 9 2017.

Dani H, Loeb S. The role of prostate cancer biomarkers in undiagnosed men. Current opinion in urology.May 2017;27(3):210-216.

Daskivich TJ, Chamie K, Kwan L, Labo J, Palvolgyi R, Dash A, . . . Litwin MS. Overtreatment of men with low-risk prostate cancer and significant comorbidity. Cancer.May 15 2011;117(10):2058-2066.

Davison BJ, Goldenberg SL. Decisional regret and quality of life after participating in medical decision-making for early-stage prostate cancer. BJU Int.Jan 2003;91(1):14-17.

Deep G, Kumar R, Nambiar DK, Jain AK, Ramteke AM, Serkova NJ, . . . Agarwal R. Silibinin inhibits hypoxia-induced HIF-1alpha-mediated signaling, angiogenesis and lipogenesis in prostate cancer cells: In vitro evidence and in vivo functional imaging and metabolomics. Molecular carcinogenesis.Mar 2017;56(3):833-848.

Demark-Wahnefried W, Polascik TJ, George SL, Switzer BR, Madden JF, Ruffin MTt, . . . Vollmer RT. Flaxseed supplementation (not dietary fat restriction) reduces prostate cancer proliferation rates in men presurgery. Cancer epidemiology, biomarkers & prevention: a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.Dec 2008;17(12):3577-3587.

Demark-Wahnefried W, Price DT, Polascik TJ, Robertson CN, Anderson EE, Paulson DF, . . . Vollmer RT. Pilot study of dietary fat restriction and flaxseed supplementation in men with prostate cancer before surgery: exploring the effects on hormonal levels, prostate-specific antigen, and histopathologic features. Urology.Jul 2001;58(1):47-52.

Denmeade SR. A Phase II Study Assessing the Safety and Efficacy of Oral Testosterone Undecanoate Followed by Enzalutamide as Therapy for Men With Metastatic Castrate Resistant Prostate Cancer. Identifier: NCT05081193. Updated 5/1/2023. Accessed 3/11/2024.

deVere White RW, Tsodikov A, Stapp EC, Soares SE, Fujii H, Hackman RM. Effects of a high dose, aglycone-rich soy extract on prostate-specific antigen and serum isoflavone concentrations in men with localized prostate cancer. Nutrition and cancer.2010;62(8):1036-1043.

Deziel B, MacPhee J, Patel K, Catalli A, Kulka M, Neto C, . . . Hurta R. American cranberry (Vaccinium macrocarpon) extract affects human prostate cancer cell growth via cell cycle arrest by modulating expression of cell cycle regulators. Food Funct.May 2012;3(5):556-564.

Deziel BA, Patel K, Neto C, Gottschall-Pass K, Hurta RA. Proanthocyanidins from the American Cranberry (Vaccinium macrocarpon) inhibit matrix metalloproteinase-2 and matrix metalloproteinase-9 activity in human prostate cancer cells via alterations in multiple cellular signalling pathways. Journal of cellular biochemistry.Oct 15 2010;111(3):742-754.

Dickerman BA, Ahearn TU, Giovannucci E, Stampfer MJ, Nguyen PL, Mucci LA, Wilson KM. Weight change, obesity and risk of prostate cancer progression among men with clinically localized prostate cancer. International journal of cancer. Journal international du cancer.Sep 01 2017;141(5):933-944.

Dietlein F, Kobe C, Neubauer S, Schmidt M, Stockter S, Fischer T, . . . Dietlein M. PSA-Stratified Performance of 18F- and 68Ga-PSMA PET in Patients with Biochemical Recurrence of Prostate Cancer. J Nucl Med.Jun 2017;58(6):947-952.

Dijkstra S, Witjes WP, Roos EP, Vijverberg PL, Geboers AD, Bruins JL, . . . Mulders PF. The AVOCAT study: Bicalutamide monotherapy versus combined bicalutamide plus dutasteride therapy for patients with locally advanced or metastatic carcinoma of the prostate-a long-term follow-up comparison and quality of life analysis. Springerplus.2016;5:653.

DiPaola RS, Chen YH, Bubley GJ, Stein MN, Hahn NM, Carducci MA, . . . Wilding G. A national multicenter phase 2 study of prostate-specific antigen (PSA) pox virus vaccine with sequential androgen ablation therapy in patients with PSA progression: ECOG 9802. Eur Urol. Sep 2015;68(3):365-371.

Dizon DS, Krilov L, Cohen E, Gangadhar T, Ganz PA, Hensing TA, . . . Masters G. Clinical Cancer Advances 2016: Annual Report on Progress Against Cancer From the American Society of Clinical Oncology. Journal of clinical oncology: official journal of the American Society of Clinical Oncology.Mar 20 2016;34(9):987-1011.

Donnelly BJ, Saliken JC, Brasher PM, Ernst SD, Rewcastle JC, Lau H, . . . Trpkov K. A randomized trial of external beam radiotherapy versus cryoablation in patients with localized prostate cancer. Cancer.Jan 15 2010;116(2):323-330.

Downer MK, Batista JL, Mucci LA, Stampfer MJ, Epstein MM, Hakansson N, . . . Andersson SO. Dairy intake in relation to prostate cancer survival. International journal of cancer. Journal international du cancer. May 01 2017;140(9):2060-2069.

Dueregger A, Heidegger I, Ofer P, Perktold B, Ramoner R, Klocker H, Eder IE. The use of dietary supplements to alleviate androgen deprivation therapy side effects during prostate cancer treatment. Nutrients.Oct 21 2014;6(10):4491-4519.

Durand M, Barret E, Galiano M, Rozet F, Sanchez-Salas R, Ahallal Y, . . . Cathelineau X. Focal cryoablation: a treatment option for unilateral low-risk prostate cancer. BJU Int.Jan 2014;113(1):56-64.

Dyck L, Mills KHG. Immune checkpoints and their inhibition in cancer and infectious diseases. European journal of immunology.May 2017;47(5):765-779.

Eapen RS, Herlemann A, Washington SL, 3rd, Cooperberg MR. Impact of the United States Preventive Services Task Force 'D' recommendation on prostate cancer screening and staging. Current opinion in urology.May 2017;27(3):205-209.

Eiber M, Fendler WP, Rowe SP, Calais J, Hofman MS, Maurer T, . . . Giesel FL. Prostate-Specific Membrane Antigen Ligands for Imaging and Therapy. J Nucl Med.Sep 2017;58(Suppl 2):67s-76s.

Eiber M, Souvatzoglou M, Maurer T, Ziegler S, Rummeny E, Schwaiger M, Beer A. Initial experience in restaging of patients with recurrent prostate cancer: Comparison of 11C-Choline-PET/MR and 11C-Choline-PET/CT. Journal of Nuclear Medicine.May 1, 2013 2013;54(supplement 2):343.

Eidelman E, Twum-Ampofo J, Ansari J, Siddiqui MM. The Metabolic Phenotype of Prostate Cancer. Frontiers in oncology.2017;7:131.

Eisenberger M, Hardy-Bessard AC, Kim CS, Geczi L, Ford D, Mourey L, . . . de Bono J. Phase III Study Comparing a Reduced Dose of Cabazitaxel (20 mg/m2) and the Currently Approved Dose (25 mg/m2) in Postdocetaxel Patients With Metastatic Castration-Resistant Prostate Cancer-PROSELICA. Journal of clinical oncology: official journal of the American Society of Clinical Oncology. Aug 15 2017:Jco2016721076.

El Touny LH, Banerjee PP. Identification of a biphasic role for genistein in the regulation of prostate cancer growth and metastasis. Cancer research.Apr 15 2009;69(8):3695-3703.

Epstein JI, Amin MB, Reuter VE, Humphrey PA. Contemporary Gleason Grading of Prostatic Carcinoma: An Update With Discussion on Practical Issues to Implement the 2014 International Society of Urological Pathology (ISUP) Consensus Conference on Gleason Grading of Prostatic Carcinoma. The American journal of surgical pathology.Apr 2017;41(4):e1-e7.

Epstein JI, Zelefsky MJ, Sjoberg DD, Nelson JB, Egevad L, Magi-Galluzzi C, . . . Klein EA. A Contemporary Prostate Cancer Grading System: A Validated Alternative to the Gleason Score. Eur Urol.Mar 2016;69(3):428-435.

Epstein MM, Kasperzyk JL, Andren O, Giovannucci EL, Wolk A, Hakansson N, . . . Mucci LA. Dietary zinc and prostate cancer survival in a Swedish cohort. The American journal of clinical nutrition.Mar 2011;93(3):586-593.

Epstein MM, Kasperzyk JL, Mucci LA, Giovannucci E, Price A, Wolk A, . . . Andren O. Dietary fatty acid intake and prostate cancer survival in Orebro County, Sweden. Am J Epidemiol.Aug 01 2012;176(3):240-252.

Estevez SV, Herranz UA, Calvo OF, Afonso Afonso FJ, Couto LS, Quintela ML, . . . Macia Escalante S. Prostate cancer perspectives after chaarted: Optimizing treatment sequence. Critical reviews in oncology/hematology. Nov 2016;107:119-127.

Etzioni R, Penson DF, Legler JM, di Tommaso D, Boer R, Gann PH, Feuer EJ. Overdiagnosis due to prostate-specific antigen screening: lessons from U.S. prostate cancer incidence trends. J Natl Cancer Inst.Jul 03 2002;94(13):981-990.

Etzioni RD, Thompson IM. What do the screening trials really tell us and where do we go from here? The Urologic clinics of North America.May 2014;41(2):223-228.

Fahmy O, Khairul-Asri MG, Hadi S, Gakis G, Stenzl A. The Role of Radical Prostatectomy and Radiotherapy in Treatment of Locally Advanced Prostate Cancer: A Systematic Review and Meta-Analysis. Urol Int.Jul 04 2017.

Feng P, Li TL, Guan ZX, Franklin RB, Costello LC. Direct effect of zinc on mitochondrial apoptogenesis in prostate cells. Prostate.Sep 01 2002;52(4):311-318.

Ferguson PJ, Kurowska EM, Freeman DJ, Chambers AF, Koropatnick J. In vivo inhibition of growth of human tumor lines by flavonoid fractions from cranberry extract. Nutrition and cancer.2006;56(1):86-94.

Fizazi K, Drake CG, Beer TM, et al. Final Analysis of the Ipilimumab Versus Placebo Following Radiotherapy Phase III Trial in Postdocetaxel Metastatic Castration-resistant Prostate Cancer Identifies an Excess of Long-term Survivors. Eur Urol. doi:10.1016/j.eururo.2020.07.032

Fizazi K, Scher HI, Molina A, Logothetis CJ, Chi KN, Jones RJ, . . . de Bono JS. Abiraterone acetate for treatment of metastatic castration-resistant prostate cancer: final overall survival analysis of the COU-AA-301 randomised, double-blind, placebo-controlled phase 3 study. The Lancet. Oncology.Oct 2012;13(10):983-992.

Fizazi K, Tran N, Fein L, Matsubara N, Rodriguez-Antolin A, Alekseev BY, . . . Chi KN. Abiraterone plus Prednisone in Metastatic, Castration-Sensitive Prostate Cancer. N Engl J Med.Jul 27 2017;377(4):352-360.

Flaig TW, Glode M, Gustafson D, van Bokhoven A, Tao Y, Wilson S, . . . Pollak M. A study of high-dose oral silybin-phytosome followed by prostatectomy in patients with localized prostate cancer. Prostate.Jun 01 2010;70(8):848-855.

Flannigan RK, Baverstock RJ. Management of post-radiation therapy complications among prostate cancer patients: A case series. Can Urol Assoc J.Sep 2014;8(9-10):E632-636.

Flesher NE, Lucia MS, Egerdie B, et al. Dutasteride in localised prostate cancer management: the REDEEM randomised, double-blind, placebo-controlled trial. Lancet. 2012; 379, 1103-11.

Fleshner K, Carlsson SV, Roobol MJ. The effect of the USPSTF PSA screening recommendation on prostate cancer incidence patterns in the USA. Nature reviews. Urology.Jan 2017;14(1):26-37.

Fong L. An Open Label, Randomized Phase 2 Trial of Prostvac and Ipilimumab as Monotherapy or in Combination for Men With Localized Prostate Cancer Undergoing Radical Prostatectomy. [Internet]. Bethesda (MD): National LIbrary of Medicine. Identifier: NCT02506114. Last updated 6/8/2017. Accessed 1/9/2018.

Food and Drug Administration. FDA approves apalutamide for metastatic castration-sensitive prostate cancer. 9/18/2019. Accessed March 25, 2022,

Franz MC, Anderle P, Burzle M, Suzuki Y, Freeman MR, Hediger MA, Kovacs G. Zinc transporters in prostate cancer. Molecular aspects of medicine.Apr-Jun 2013;34(2-3):735-741.

Freiberger C, Berneking V, Vogeli TA, Kirschner-Hermanns R, Eble MJ, Pinkawa M. Long-term prognostic significance of rising PSA levels following radiotherapy for localized prostate cancer - focus on overall survival. Radiation oncology (London, England).Jun 14 2017;12(1):98.

Fulgham PF, Rukstalis DB, Turkbey IB, Rubenstein JN, Taneja S, Carroll PR, . . . Eggener S. AUA Policy Statement on the Use of Multiparametric Magnetic Resonance Imaging in the Diagnosis, Staging and Management of Prostate Cancer. J Urol.May 05 2017.

Gade TP, Hassen W, Santos E, Gunset G, Saudemont A, Gong MC, . . . Sadelain M. Targeted elimination of prostate cancer by genetically directed human T lymphocytes. Cancer research.Oct 01 2005;65(19):9080-9088.

Galasso F, Giannella R, Bruni P, Giulivo R, Barbini VR, Disanto V, . . . Sepe G. PCA3: a new tool to diagnose prostate cancer (PCa) and a guidance in biopsy decisions. Preliminary report of the UrOP study. Archivio italiano di urologia, andrologia: organo ufficiale [di] Societa italiana di ecografia urologica e nefrologica / Associazione ricerche in urologia.Mar 2010;82(1):5-9.

Galet C, Gollapudi K, Stepanian S, Byrd JB, Henning SM, Grogan T, . . . Aronson WJ. Effect of a low-fat fish oil diet on proinflammatory eicosanoids and cell-cycle progression score in men undergoing radical prostatectomy. Cancer prevention research (Philadelphia, Pa.).Jan 2014;7(1):97-104.

Galvao DA, Taaffe DR, Spry N, Gardiner RA, Taylor R, Risbridger GP, . . . Newton RU. Enhancing active surveillance of prostate cancer: the potential of exercise medicine. Nature reviews. Urology.May 2016;13(5):258-265.

Gandaglia G, Fossati N, Stabile A, Bandini M, Rigatti P, Montorsi F, Briganti A. Radical Prostatectomy in Men with Oligometastatic Prostate Cancer: Results of a Single-institution Series with Long-term Follow-up. Eur Urol.Aug 2017;72(2):289-292.

Garcia-Barreras S, Sanchez-Salas R, Sivaraman A, Barret E, Secin F, Nunes-Silva I, . . . Cathelineau X. Partial gland ablation versus radical prostatectomy Comparative Analysis of Partial Gland Ablation and Radical Prostatectomy to Treat Low- and Intermediate-risk Prostate Cancer: Oncologic and Functional Outcomes. J Urol.Aug 17 2017.

Garisto JD, Klotz L. Active Surveillance for Prostate Cancer: How to Do It Right. Oncology (Williston Park, N.Y.).May 15 2017;31(5):333-340, 345.

Geybels MS, Neuhouser ML, Wright JL, Stott-Miller M, Stanford JL. Coffee and tea consumption in relation to prostate cancer prognosis. Cancer Causes Control.Nov 2013;24(11):1947-1954.

Gilbert DC, Duong T, Kynaston HG, Alhasso AA, Cafferty FH, Rosen SD, . . . Abel PD. Quality-of-life outcomes from the Prostate Adenocarcinoma: TransCutaneous Hormones (PATCH) trial evaluating luteinising hormone-releasing hormone agonists versus transdermal oestradiol for androgen suppression in advanced prostate cancer. BJU Int.May 2017;119(5):667-675.

Gillessen S, Attard G, Beer TM, Beltran H, Bossi A, Bristow R, . . . Omlin A. Management of Patients with Advanced Prostate Cancer: The Report of the Advanced Prostate Cancer Consensus Conference APCCC 2017. Eur Urol.Jun 24 2017.

Goel A, Aggarwal BB. Curcumin, the golden spice from Indian saffron, is a chemosensitizer and radiosensitizer for tumors and chemoprotector and radioprotector for normal organs. Nutrition and cancer. 2010;62(7):919-930.

Golbari NM, Katz AE. Salvage Therapy Options for Local Prostate Cancer Recurrence After Primary Radiotherapy: a Literature Review. Current urology reports.Aug 2017;18(8):63.

Goldenberg MG, Goldenberg L, Grantcharov TP. Surgeon Performance Predicts Early Continence After Robot-Assisted Radical Prostatectomy. Journal of endourology / Endourological Society. Sep 2017;31(9):858-863.

Golla V, Kaplan AL. Testosterone Therapy on Active Surveillance and Following Definitive Treatment for Prostate Cancer. Current urology reports.Jul 2017;18(7):49.

Gonzalez A, Peters U, Lampe JW, White E. Zinc intake from supplements and diet and prostate cancer. Nutrition and cancer.2009;61(2):206-215.

Goodall J, Mateo J, Yuan W, Mossop H, Porta N, Miranda S, . . . de Bono JS. Circulating Free DNA to Guide Prostate Cancer Treatment with PARP Inhibition. Cancer Discov.Apr 27 2017.

Gorawara-Bhat R, O'Muircheartaigh S, Mohile S, Dale W. Patients' perceptions and attitudes on recurrent prostate cancer and hormone therapy: Qualitative comparison between decision-aid and control groups. Journal of geriatric oncology.Jun 08 2017.

Gordetsky J, Epstein J. Grading of prostatic adenocarcinoma: current state and prognostic implications. Diagnostic pathology.Mar 09 2016;11:25.

Goyal NK, Kumar A, Trivedi S, Dwivedi US, Singh PB. Surgical complications of radical retropubic prostatectomy: A single institutional experience of seven years. Indian journal of urology: IJU: journal of the Urological Society of India.Oct 2007;23(4):369-371.

Graff JN, Alumkal JJ, Drake CG, Thomas GV, Redmond WL, Farhad M, . . . Beer TM. Early evidence of anti-PD-1 activity in enzalutamide-resistant prostate cancer. Oncotarget.Aug 16 2016;7(33):52810-52817.

Gu Z, Suburu J, Chen H, Chen YQ. Mechanisms of omega-3 polyunsaturated fatty acids in prostate cancer prevention. Biomed Res Int.2013;2013:824563.

Guess BW, Scholz MC, Strum SB, Lam RY, Johnson HJ, Jennrich RI. Modified citrus pectin (MCP) increases the prostate-specific antigen doubling time in men with prostate cancer: a phase II pilot study. Prostate Cancer Prostatic Dis.2003;6(4):301-304.

Gulley JL. Phase I/II Study of PROSTVAC in Combination With Nivolumab in Men With Prostate Cancer. [Internet]. Bethesda (MD): National Library of Medicine. Identifier: NCT02933255. Last updated 10/19/2017. Accessed 1/9/2018.

Gupta D, Salmane C, Slovin S, Steingart RM. Cardiovascular Complications of Androgen Deprivation Therapy for Prostate Cancer. Current treatment options in cardiovascular medicine. Aug 2017;19(8):61.

Hackett GI. Testosterone Replacement Therapy and Mortality in Older Men. Drug safety: an international journal of medical toxicology and drug experience.Feb 2016;39(2):117-130.

Hallemeier CL, Kohli M, Chandan VS, Miller RC, Choo R. Multiple urinary bladder masses from metastatic prostate adenocarcinoma. Rare tumors.Dec 31 2010;2(4):e65.

Hamdy FC, Donovan JL, Lane JA, Mason M, Metcalfe C, Holding P, . . . Neal DE. 10-Year Outcomes after Monitoring, Surgery, or Radiotherapy for Localized Prostate Cancer. N Engl J Med. Oct 13 2016;375(15):1415-1424.

Hamilton-Reeves JM, Banerjee S, Banerjee SK, Holzbeierlein JM, Thrasher JB, Kambhampati S, . . . Van Veldhuizen P. Short-term soy isoflavone intervention in patients with localized prostate cancer: a randomized, double-blind, placebo-controlled trial. PloS one.2013;8(7):e68331.

Hamilton K, Bennett NC, Purdie G, Herst PM. Standardized cranberry capsules for radiation cystitis in prostate cancer patients in New Zealand: a randomized double blinded, placebo controlled pilot study. Supportive care in cancer: official journal of the Multinational Association of Supportive Care in Cancer.Jan 2015;23(1):95-102.

Hamstra DA, Mariados N, Sylvester J, Shah D, Karsh L, Hudes R, . . . Michalski J. Continued Benefit to Rectal Separation for Prostate Radiation Therapy: Final Results of a Phase III Trial. International journal of radiation oncology, biology, physics.Apr 01 2017;97(5):976-985.

Hannoun-Levi JM. Brachytherapy for prostate cancer: Present and future. Cancer radiotherapie: journal de la Societe francaise de radiotherapie oncologique.Aug 25 2017.

Hart NH, Galvao DA, Newton RU. Exercise medicine for advanced prostate cancer. Current opinion in supportive and palliative care.Sep 2017;11(3):247-257.

Hatakeyama S, Yoneyama T, Tobisawa Y, Ohyama C. Recent progress and perspectives on prostate cancer biomarkers. Int J Clin Oncol.Apr 2017;22(2):214-221.

He K, Hu H, Ye S, Wang H, Cui R, Yi L. The effect of metformin therapy on incidence and prognosis in prostate cancer: A systematic review and meta-analysis. Scientific Reports. 2019/02/18 2019;9(1):2218. doi:10.1038/s41598-018-38285-w.

Hebert JR, Hurley TG, Harmon BE, Heiney S, Hebert CJ, Steck SE. A diet, physical activity, and stress reduction intervention in men with rising prostate-specific antigen after treatment for prostate cancer. Cancer epidemiology.Apr 2012;36(2):e128-136.

Heery CR, Madan RA, Stein MN, Stadler WM, Di Paola RS, Rauckhorst M, . . . Gulley JL. Samarium-153-EDTMP (Quadramet(R)) with or without vaccine in metastatic castration-resistant prostate cancer: A randomized Phase 2 trial. Oncotarget.Oct 18 2016;7(42):69014-69023.

Hegemann M, Bedke J, Stenzl A, Todenhofer T. Denosumab treatment in the management of patients with advanced prostate cancer: clinical evidence and experience. Therapeutic advances in urology.Mar-Apr 2017;9(3-4):81-88.

Helfand BT, Roehl KA, Cooper PR, McGuire BB, Fitzgerald LM, Cancel-Tassin G, . . . Catalona WJ. Associations of prostate cancer risk variants with disease aggressiveness: results of the NCI-SPORE Genetics Working Group analysis of 18,343 cases. Human genetics.Apr 2015;134(4):439-450.

Helleday T. PARP inhibitor receives FDA breakthrough therapy designation in castration resistant prostate cancer: beyond germline BRCA mutations. Ann Oncol.May 2016;27(5):755-757.

Henning SM, Wang P, Said JW, Huang M, Grogan T, Elashoff D, . . . Aronson WJ. Randomized clinical trial of brewed green and black tea in men with prostate cancer prior to prostatectomy. Prostate.Apr 01 2015;75(5):550-559.

Hessels D, Klein Gunnewiek JM, van Oort I, Karthaus HF, van Leenders GJ, van Balken B, . . . Schalken JA. DD3(PCA3)-based molecular urine analysis for the diagnosis of prostate cancer. Eur Urol.Jul 2003;44(1):8-15; discussion 15-16.

Hevia D, Gonzalez-Menendez P, Fernandez-Fernandez M, Cueto S, Rodriguez-Gonzalez P, Garcia-Alonso JI, . . . Sainz RM. Melatonin Decreases Glucose Metabolism in Prostate Cancer Cells: A (13)C Stable Isotope-Resolved Metabolomic Study. International journal of molecular sciences.Jul 26 2017;18(8).

Higano C, Farrell TW. Overview of approach to prostate cancer survivors. UpToDate. Updated 9/15/2022. Accessed 2/28/2024.

Hisano M, Bruschini H, Nicodemo AC, Srougi M. Cranberries and lower urinary tract infection prevention. Clinics (Sao Paulo, Brazil).2012;67(6):661-668.

Ho T, Howard LE, Vidal AC, Gerber L, Moreira D, McKeever M, . . . Freedland SJ. Smoking and risk of low- and high-grade prostate cancer: results from the REDUCE study. Clinical cancer research: an official journal of the American Association for Cancer Research.Oct 15 2014;20(20):5331-5338.

Ho TH, Nunez-Nateras R, Hou YX, Bryce AH, Northfelt DW, Dueck AC, . . . Castle EP. A Study of Combination Bicalutamide and Raloxifene for Patients With Castration-Resistant Prostate Cancer. Clinical genitourinary cancer.Apr 2017;15(2):196-202.e191.

Holmboe ES, Concato J. Treatment decisions for localized prostate cancer: asking men what's important. Journal of general internal medicine.Oct 2000;15(10):694-701.

Holmes-Rovner M, Srikanth A, Henry SG, Langford A, Rovner DR, Fagerlin A. Decision aid use during post-biopsy consultations for localized prostate cancer. Health expectations: an international journal of public participation in health care and health policy.Sep 07 2017.

Holmes JA, Bensen JT, Mohler JL, Song L, Mishel MH, Chen RC. Quality of care received and patient-reported regret in prostate cancer: Analysis of a population-based prospective cohort. Cancer.Jan 01 2017;123(1):138-143.

Howard LE, Moreira D, De Hoedt A, Aronson WJ, Kane CJ, Amling CL, . . . Freedland SJ. Thresholds for PSA doubling time in men with non-metastatic castration-resistant prostate cancer. BJU Int.Mar 28 2017.

Howrey BT, Kuo YF, Lin YL, Goodwin JS. The impact of PSA screening on prostate cancer mortality and overdiagnosis of prostate cancer in the United States. J Gerontol A Biol Sci Med Sci. Jan 2013;68(1):56-61.

Hsu JW, Yasmin-Karim S, King MR, Wojciechowski JC, Mickelsen D, Blair ML, . . . Lee YF. Suppression of prostate cancer cell rolling and adhesion to endothelium by 1alpha,25-dihydroxyvitamin D3. Am J Pathol.Feb 2011;178(2):872-880.

Hudson J, Cruickshank M, Quinton R, et al. Symptomatic benefits of testosterone treatment in patient subgroups: a systematic review, individual participant data meta-analysis, and aggregate data meta-analysis. Lancet Healthy Longev. Oct 2023;4(10):e561-e572. doi:10.1016/s2666-7568(23)00169-1.

Humphrey PA. Gleason grading and prognostic factors in carcinoma of the prostate. Mod Pathol.Mar 2004;17(3):292-306.

Hvid T, Lindegaard B, Winding K, Iversen P, Brasso K, Solomon TP, . . . Hojman P. Effect of a 2-year home-based endurance training intervention on physiological function and PSA doubling time in prostate cancer patients. Cancer Causes Control.Feb 2016;27(2):165-174.

Ide H, Tokiwa S, Sakamaki K, Nishio K, Isotani S, Muto S, . . . Horie S. Combined inhibitory effects of soy isoflavones and curcumin on the production of prostate-specific antigen. Prostate.Jul 01 2010;70(10):1127-1133.

Israeli RS. Managing bone loss and bone metastases in prostate cancer patients: a focus on bisphosphonate therapy. Rev Urol.Spring 2008;10(2):99-110.

Ito K, Fujizuka Y, Ishikura K, Cook B. Next-generation prostate-specific antigen test: precursor form of prostate-specific antigen. Int J Clin Oncol.Oct 2014;19(5):782-792.

Jackson CL, Dreaden TM, Theobald LK, Tran NM, Beal TL, Eid M, . . . Mohnen D. Pectin induces apoptosis in human prostate cancer cells: correlation of apoptotic function with pectin structure. Glycobiology.Aug 2007;17(8):805-819.

Jacob SA, Khan TM, Lee LH. The Effect of Green Tea Consumption on Prostate Cancer Risk and Progression: A Systematic Review. Nutrition and cancer.Apr 2017;69(3):353-364.

Jacobs EJ, Newton CC, Stevens VL, Campbell PT, Freedland SJ, Gapstur SM. Daily aspirin use and prostate cancer-specific mortality in a large cohort of men with nonmetastatic prostate cancer. Journal of clinical oncology: official journal of the American Society of Clinical Oncology.Nov 20 2014;32(33):3716-3722.

Jambor I, Bostrom PJ, Taimen P, Syvanen K, Kahkonen E, Kallajoki M, . . . Aronen HJ. Novel biparametric MRI and targeted biopsy improves risk stratification in men with a clinical suspicion of prostate cancer (IMPROD Trial). Journal of magnetic resonance imaging: JMRI. Oct 2017;46(4):1089-1095.

James ND, de Bono JS, Spears MR, Clarke NW, Mason MD, Dearnaley DP, . . . Sydes MR. Abiraterone for Prostate Cancer Not Previously Treated with Hormone Therapy. N Engl J Med.Jul 27 2017;377(4):338-351.

James ND, Sydes MR, Clarke NW, Mason MD, Dearnaley DP, Spears MR, . . . Parmar MK. Addition of docetaxel, zoledronic acid, or both to first-line long-term hormone therapy in prostate cancer (STAMPEDE): survival results from an adaptive, multiarm, multistage, platform randomised controlled trial. Lancet.Mar 19 2016;387(10024):1163-1177.

Jang TL, Bekelman JE, Liu Y, Bach PB, Basch EM, Elkin EB, . . . Schrag D. Physician visits prior to treatment for clinically localized prostate cancer. Archives of internal medicine.Mar 08 2010;170(5):440-450.

Jiang J, Eliaz I, Sliva D. Synergistic and additive effects of modified citrus pectin with two polybotanical compounds, in the suppression of invasive behavior of human breast and prostate cancer cells. Integrative cancer therapies.Mar 2013;12(2):145-152.

Johns Hopkins. Hormone Therapy for Prostate Cancer. Published 2020. Accessed August 18, 2020.

Johnson ED, Butler K, Gupta S. Bone Health in Patients With Prostate Cancer: An Evidence-Based Algorithm. Fed Pract. Aug 2021;38(Suppl 3):S20-S26. doi:10.12788/fp.0155

Jones MR, Joshu CE, Kanarek N, Navas-Acien A, Richardson KA, Platz EA. Cigarette Smoking and Prostate Cancer Mortality in Four US States, 1999-2010. Preventing chronic disease.Apr 14 2016;13:E51.

Jones RA, Hollen PJ, Wenzel J, Weiss G, Song D, Sims T, Petroni G. Understanding Advanced Prostate Cancer Decision Making Utilizing an Interactive Decision Aid. Cancer nursing.Nov 01 2016.

Jones TA, Chin J, McLeod D, Barkin J, Pantuck A, Marks LS. High-Intensity Focused Ultrasound for Radio-recurrent Prostate Cancer: A North American Clinical Trial. J Urol.Jun 23 2017.

Jones TA, Radtke JP, Hadaschik B, Marks LS. Optimizing safety and accuracy of prostate biopsy. Current opinion in urology.Sep 2016;26(5):472-480.

Joshua AM, Armstrong A, Crumbaker M, et al. Statin and metformin use and outcomes in patients with castration-resistant prostate cancer treated with enzalutamide: A meta-analysis of AFFIRM, PREVAIL and PROSPER. European journal of cancer (Oxford, England: 1990). Jul 2022;170:285-295. doi:10.1016/j.ejca.2022.04.005.

Junghans RP, Ma Q, Rathore R, Gomes EM, Bais AJ, Lo AS, . . . Cohen SI. Phase I Trial of Anti-PSMA Designer CAR-T Cells in Prostate Cancer: Possible Role for Interacting Interleukin 2-T Cell Pharmacodynamics as a Determinant of Clinical Response. Prostate. Oct 2016;76(14):1257-1270.

Kajla P, Sharma A, Sood DR. Flaxseed-a potential functional food source. Journal of food science and technology.Apr 2015;52(4):1857-1871.

Kanthabalan A, Peters M, Van Vulpen M, McCartan N, Hindley RG, Emara A, . . . Ahmed HU. Focal salvage high-intensity focused ultrasound in radiorecurrent prostate cancer. BJU Int.Aug 2017;120(2):246-256.

Kaplan-Marans E, Zhang TR, Hu JC. Oncologic Outcomes of Testosterone Therapy for Men on Active Surveillance for Prostate Cancer: A Population-based Analysis. European Urology Open Science. 2024;60:36-43. 

Kardoust Parizi M, Abufaraj M, Fajkovic H, et al. Oncological safety of testosterone replacement therapy in prostate cancer survivors after definitive local therapy: A systematic literature review and meta-analysis. Urologic oncology. Oct 2019;37(10):637-646. doi:10.1016/j.urolonc.2019.06.007.

Keilani M, Hasenoehrl T, Baumann L, Ristl R, Schwarz M, Marhold M, . . . Crevenna R. Effects of resistance exercise in prostate cancer patients: a meta-analysis. Supportive care in cancer: official journal of the Multinational Association of Supportive Care in Cancer.Sep 2017;25(9):2953-2968.

Keizman D. Phase III, Single-Center, Open Label, Trial Evaluating the Safety and Efficacy of PectaSol-C Modified Citrus Pectin on PSA Kinetics in Prostate Cancer in the Setting of Serial Increases in PSA. [Internet]. Bethesda (MD): National LIbrary of Medicine. Identifier: NCT01681823. Last updated 5/30/2017. Accessed 9/15/2017.

Kenfield SA, Stampfer MJ, Chan JM, Giovannucci E. Smoking and prostate cancer survival and recurrence. JAMA.Jun 22 2011;305(24):2548-2555.

Kim DK, Lee JY, Kim KJ, et al. Effect of Androgen-Deprivation Therapy on Bone Mineral Density in Patients with Prostate Cancer: A Systematic Review and Meta-Analysis. Journal of Clinical Medicine. 2019;8(1):113.

Kim HJ, Phak JH, Kim WC. Hypofractionated stereotactic body radiotherapy in low- and intermediate-risk prostate carcinoma. Radiation oncology journal.Dec 2016;34(4):260-264.

Kim SP, Gross CP, Nguyen PL, Smaldone MC, Thompson RH, Shah ND, . . . Tilburt JC. Specialty bias in treatment recommendations and quality of life among radiation oncologists and urologists for localized prostate cancer. Prostate Cancer Prostatic Dis.Jun 2014;17(2):163-169.

Kim TH, Jeon HG, Jeong BC, Seo SI, Jeon SS, Choi HY, Lee HM. Development of a new nomogram to predict insignificant prostate cancer in patients undergoing radical prostatectomy. Scand J Urol.Feb 2017;51(1):27-32.

Kim YS, Rhim H, Choi MJ, Lim HK, Choi D. High-intensity focused ultrasound therapy: an overview for radiologists. Korean journal of radiology.Jul-Aug 2008;9(4):291-302.

Kirsh VA, Peters U, Mayne ST, Subar AF, Chatterjee N, Johnson CC, Hayes RB. Prospective study of fruit and vegetable intake and risk of prostate cancer. J Natl Cancer Inst.Aug 01 2007;99(15):1200-1209.

Kishan AU, King CR. Stereotactic Body Radiotherapy for Low- and Intermediate-Risk Prostate Cancer. Seminars in radiation oncology.Jul 2017;27(3):268-278.

Kloss CC, Condomines M, Cartellieri M, Bachmann M, Sadelain M. Combinatorial antigen recognition with balanced signaling promotes selective tumor eradication by engineered T cells. Nat Biotechnol.Jan 2013;31(1):71-75.

Koch MO, Cho JS, Kaimakliotis HZ, Cheng L, Sangale Z, Brawer M, . . . Stone S. Use of the cell cycle progression (CCP) score for predicting systemic disease and response to radiation of biochemical recurrence. Cancer biomarkers: section A of Disease markers.Jun 07 2016;17(1):83-88.

Koskela K, Palmgren JE, Heikkila J, Virsunen H, Sailas L, Auvinen P, . . . Kataja V. Hypofractionated stereotactic body radiotherapy for localized prostate cancer - first Nordic clinical experience. Acta oncologica (Stockholm, Sweden).Jul 2017;56(7):978-983.

Krugh M, Langaker MD. Dual Energy X-ray Absorptiometry. StatPearls. 2022.

Ku JY, Lee CH, Lee JZ, Ha HK. Comparison of functional outcomes between laparoscopic radical prostatectomy and robot-assisted laparoscopic radical prostatectomy: a propensity score-matched comparison study. Asia Pac J Clin Oncol.Jun 2017;13(3):212-218.

Kucuk O, Sarkar FH, Sakr W, Djuric Z, Pollak MN, Khachik F, . . . Wood DP, Jr. Phase II randomized clinical trial of lycopene supplementation before radical prostatectomy. Cancer epidemiology, biomarkers & prevention: a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. Aug 2001;10(8):861-868.

Kulkarni HR, Singh A, Schuchardt C, Niepsch K, Sayeg M, Leshch Y, . . . Baum RP. PSMA-Based Radioligand Therapy for Metastatic Castration-Resistant Prostate Cancer: The Bad Berka Experience Since 2013. J Nucl Med. Oct 2016;57(Suppl 3):97s-104s.

Kumar NB, Besterman-Dahan K, Kang L, Pow-Sang J, Xu P, Allen K, . . . Krischer JP. Results of a Randomized Clinical Trial of the Action of Several Doses of Lycopene in Localized Prostate Cancer: Administration Prior to Radical Prostatectomy. Clinical medicine. Urology [electronic resource].Apr 16 2008;1:1-14.

Kumar NB, Pow-Sang J, Egan KM, Spiess PE, Dickinson S, Salup R, . . . Schell MJ. Randomized, Placebo-Controlled Trial of Green Tea Catechins for Prostate Cancer Prevention. Cancer prevention research (Philadelphia, Pa.).Oct 2015;8(10):879-887.

Kumar NB, Pow-Sang J, Spiess PE, Park J, Salup R, Williams CR, . . . Schell MJ. Randomized, placebo-controlled trial evaluating the safety of one-year administration of green tea catechins. Oncotarget.Oct 25 2016;7(43):70794-70802.

Kwan W, Duncan G, Van Patten C, Liu M, Lim J. A phase II trial of a soy beverage for subjects without clinical disease with rising prostate-specific antigen after radical radiation for prostate cancer. Nutrition and cancer.2010;62(2):198-207.

Lardas M, Liew M, van den Bergh RC, De Santis M, Bellmunt J, Van den Broeck T, . . . Bourke L. Quality of Life Outcomes after Primary Treatment for Clinically Localised Prostate Cancer: A Systematic Review. Eur Urol.Jul 27 2017.

Lazarevic B, Boezelijn G, Diep LM, Kvernrod K, Ogren O, Ramberg H, . . . Karlsen SJ. Efficacy and safety of short-term genistein intervention in patients with localized prostate cancer prior to radical prostatectomy: a randomized, placebo-controlled, double-blind Phase 2 clinical trial. Nutrition and cancer.2011;63(6):889-898.

Lazzeroni M, Guerrieri-Gonzaga A, Gandini S, Johansson H, Serrano D, Cazzaniga M, . . . Bonanni B. A Presurgical Study of Oral Silybin-Phosphatidylcholine in Patients with Early Breast Cancer. Cancer prevention research (Philadelphia, Pa.).Jan 2016;9(1):89-95.

Lecarpentier J, Silvestri V, Kuchenbaecker KB, Barrowdale D, Dennis J, McGuffog L, . . . Ottini L. Prediction of Breast and Prostate Cancer Risks in Male BRCA1 and BRCA2 Mutation Carriers Using Polygenic Risk Scores. Journal of clinical oncology: official journal of the American Society of Clinical Oncology.Jul 10 2017;35(20):2240-2250.

Leclere L, Cutsem PV, Michiels C. Anti-cancer activities of pH- or heat-modified pectin. Frontiers in Pharmacology.2013;4.

Lee DJ, Mallin K, Graves AJ, Chang SS, Penson DF, Resnick MJ, Barocas DA. Recent changes in prostate cancer screening practices and prostate cancer epidemiology. J Urol.May 25 2017.

Lee SH, Seo HJ, Lee NR, Son SK, Kim DK, Rha KH. Robot-assisted radical prostatectomy has lower biochemical recurrence than laparoscopic radical prostatectomy: Systematic review and meta-analysis. Investigative and clinical urology.May 2017;58(3):152-163.

Lee TK, Breau RH, Mallick R, Eapen L. A systematic review of expanded prostate cancer index composite (EPIC) quality of life after surgery or radiation treatment. The Canadian journal of urology.Feb 2015;22(1):7599-7606.

Lee YH, Kwak J, Choi HK, Choi KC, Kim S, Lee J, . . . Yoon HG. EGCG suppresses prostate cancer cell growth modulating acetylation of androgen receptor by anti-histone acetyltransferase activity. Int J Mol Med.Jul 2012;30(1):69-74.

Legisi L, DeSa E, Qureshi MN. Use of the Prostate Core Mitomic Test in Repeated Biopsy Decision-Making: Real-World Assessment of Clinical Utility in a Multicenter Patient Population. American health & drug benefits.Dec 2016;9(9):497-502.

Lesinski GB, Reville PK, Mace TA, Young GS, Ahn-Jarvis J, Thomas-Ahner J, . . . Clinton SK. Consumption of soy isoflavone enriched bread in men with prostate cancer is associated with reduced proinflammatory cytokines and immunosuppressive cells. Cancer prevention research (Philadelphia, Pa.).Nov 2015;8(11):1036-1044.

Levesque C, Nelson PS. Cellular Constituents of the Prostate Stroma: Key Contributors to Prostate Cancer Progression and Therapy Resistance. Cold Spring Harbor perspectives in medicine. May 10 2017.

Li Y, Ahmad A, Kong D, Bao B, Sarkar FH. Recent progress on nutraceutical research in prostate cancer. Cancer metastasis reviews.Sep 2014;33(2-3):629-640.

Lian WQ, Luo F, Song XL, Lu YJ, Zhao SC. Gonorrhea and Prostate Cancer Incidence: An Updated Meta-Analysis of 21 Epidemiologic Studies. Med Sci Monit.Jul 01 2015;21:1902-1910.

Liang P, Henning SM, Schokrpur S, Wu L, Doan N, Said J, . . . Aronson WJ. Effect of Dietary Omega-3 Fatty Acids on Tumor-Associated Macrophages and Prostate Cancer Progression. Prostate.Oct 2016;76(14):1293-1302.

Lilleby W, Gaudernack G, Brunsvig PF, Vlatkovic L, Schulz M, Mills K, . . . Inderberg EM. Phase I/IIa clinical trial of a novel hTERT peptide vaccine in men with metastatic hormone-naive prostate cancer. Cancer Immunol Immunother.Jul 2017;66(7):891-901.

Lin PH, Aronson W, Freedland SJ. Nutrition, dietary interventions and prostate cancer: the latest evidence. BMC medicine.Jan 08 2015;13:3.

Litwin MS, Tan HJ. The Diagnosis and Treatment of Prostate Cancer: A Review. JAMA.Jun 27 2017;317(24):2532-2542.

Liu B, Mao Q, Cao M, Xie L. Cruciferous vegetables intake and risk of prostate cancer: a meta-analysis. Int J Urol.Feb 2012;19(2):134-141.

Liu N, Feng Y, Ma X, Ma F. Prevalence of testosterone deficiency among US adult males. The aging male : the official journal of the International Society for the Study of the Aging Male. Dec 2022;25(1):278-280. doi:10.1080/13685538.2022.2130236.

Liu Q, Tong D, Liu G, Xu J, Do K, Geary K, . . . Jiang J. Metformin reverses prostate cancer resistance to enzalutamide by targeting TGF-beta1/STAT3 axis-regulated EMT. Cell death & disease.Aug 24 2017;8(8):e3007.

Lloyd JC, Masko EM, Wu C, Keenan MM, Pilla DM, Aronson WJ, . . . Freedland SJ. Fish oil slows prostate cancer xenograft growth relative to other dietary fats and is associated with decreased mitochondrial and insulin pathway gene expression. Prostate Cancer Prostatic Dis. Dec 2013;16(4):285-291.

Loeb S, Bjurlin MA, Nicholson J, Tammela TL, Penson DF, Carter HB, . . . Etzioni R. Overdiagnosis and overtreatment of prostate cancer. Eur Urol.Jun 2014;65(6):1046-1055.

Loeb S, Catalona WJ. The Prostate Health Index: a new test for the detection of prostate cancer. Therapeutic advances in urology.Apr 2014;6(2):74-77.

Loughlin KR. PSA velocity: a systematic review of clinical applications. Urologic oncology.Nov 2014;32(8):1116-1125.

Lowentritt B, Brown G, Pilon D, et al. Real-World Prostate-Specific Antigen Response and Treatment Adherence of Apalutamide in Patients with Non-Metastatic Castration-Resistant Prostate Cancer. Urology. Mar 19 2022;doi:10.1016/j.urology.2022.02.024

Lowrance WT, Scardino PT. Predictive models for newly diagnosed prostate cancer patients. Rev Urol.Summer 2009;11(3):117-126.

Ma Q, Gomes EM, Lo AS, Junghans RP. Advanced generation anti-prostate specific membrane antigen designer T cells for prostate cancer immunotherapy. Prostate.Feb 2014;74(3):286-296.

Macedo F, Ladeira K, Pinho F, Saraiva N, Bonito N, Pinto L, Goncalves F. Bone Metastases: An Overview. Oncology reviews.Mar 03 2017;11(1):321.

Madan RA. Docetaxel and Prostvac for Metastatic Castration Sensitive Prostate Cancer. [Internet]. Bethesda (MD): National Library of Medicine. Identifier: NCT02649855. Last updated 11/24/2017. Accessed 1/9/2018.

Madan RA, Gulley JL. Prostate cancer immunotherapy: the path forward. Current opinion in supportive and palliative care.Sep 2017;11(3):225-230.

Magnuson WJ, Mahal A, Yu JB. Emerging Technologies and Techniques in Radiation Therapy. Seminars in radiation oncology.Jan 2017;27(1):34-42.

Mahammedi H, Planchat E, Pouget M, Durando X, Cure H, Guy L, . . . Eymard JC. The New Combination Docetaxel, Prednisone and Curcumin in Patients with Castration-Resistant Prostate Cancer: A Pilot Phase II Study. Oncology.2016;90(2):69-78.

Malatesta M, Mannello F, Luchetti F, Marcheggiani F, Condemi L, Papa S, Gazzanelli G. Prostate-specific antigen synthesis and secretion by human placenta: a physiological kallikrein source during pregnancy. The Journal of clinical endocrinology and metabolism.Jan 2000;85(1):317-321.

Malietzis G, Monzon L, Hand J, Wasan H, Leen E, Abel M, . . . Abel P. High-intensity focused ultrasound: advances in technology and experimental trials support enhanced utility of focused ultrasound surgery in oncology. The British journal of radiology.Apr 2013;86(1024):20130044.

Malik A, Afaq F, Sarfaraz S, Adhami VM, Syed DN, Mukhtar H. Pomegranate fruit juice for chemoprevention and chemotherapy of prostate cancer. Proceedings of the National Academy of Sciences of the United States of America. Oct 11 2005;102(41):14813-14818.

Maluf FC, Smaletz O, Herchenhorn D. Castration-resistant prostate cancer: systemic therapy in 2012. Clinics (Sao Paulo, Brazil).2012;67(4):389-394.

Mandl SJ, Rountree RB, Dela Cruz TB, Foy SP, Cote JJ, Gordon EJ, . . . Franzusoff A. Elucidating immunologic mechanisms of PROSTVAC cancer immunotherapy. Journal for immunotherapy of cancer.2014;2(1):34.

Manivannan E, Amawi H, Hussein N, Karthikeyan C, Fetcenko A, Narayana Moorthy NSH, . . . Tiwari AK. Design and discovery of silybin analogues as antiproliferative compounds using a ring disjunctive - Based, natural product lead optimization approach. European journal of medicinal chemistry.Jun 16 2017;133:365-378.

Marks L, Young S, Natarajan S. MRI-ultrasound fusion for guidance of targeted prostate biopsy. Current opinion in urology.Jan 2013;23(1):43-50.

Marshall DT, Savage SJ, Garrett-Mayer E, Keane TE, Hollis BW, Horst RL, . . . Gattoni-Celli S. Vitamin D3 supplementation at 4000 international units per day for one year results in a decrease of positive cores at repeat biopsy in subjects with low-risk prostate cancer under active surveillance. The Journal of clinical endocrinology and metabolism.Jul 2012;97(7):2315-2324.

Martignano F, Rossi L, Maugeri A, Galla V, Conteduca V, De Giorgi U, . . . Schepisi G. Urinary RNA-based biomarkers for prostate cancer detection. Clinica chimica acta; international journal of clinical chemistry.Aug 12 2017;473:96-105.

Masterson TA, Bianco FJ, Jr., Vickers AJ, DiBlasio CJ, Fearn PA, Rabbani F, . . . Scardino PT. The association between total and positive lymph node counts, and disease progression in clinically localized prostate cancer. J Urol.Apr 2006;175(4):1320-1324; discussion 1324-1325.

Mateo J, Boysen G, Barbieri CE, Bryant HE, Castro E, Nelson PS, . . . de Bono JS. DNA Repair in Prostate Cancer: Biology and Clinical Implications. European urology.Mar 2017;71(3):417-425.

Mateo J, Carreira S, Sandhu S, Miranda S, Mossop H, Perez-Lopez R, . . . de Bono JS. DNA-Repair Defects and Olaparib in Metastatic Prostate Cancer. N Engl J Med.Oct 29 2015;373(18):1697-1708.

Matthew R. Smith M.D. PD, Francis J. McGovern M.D., Mary Anne Fallon L.P.N., David Schoenfeld Ph.D., Philip W. Kantoff M.D., Joel S. Finkelstein M.D. Low bone mineral density in hormone-naïve men with prostate carcinoma. Cancer. 15 June 2001 91(12):2238-2245.

Mayo Clinic. Prostate Cancer: Symptoms & causes. 2/15/2018. Accessed 2/15/2018.

Mayo Clinic. Prostatitis: Symptoms & causes. 11/23/2016. Accessed 8/17/2017.

Mayo JC, Hevia D, Quiros-Gonzalez I, Rodriguez-Garcia A, Gonzalez-Menendez P, Cepas V, . . . Sainz RM. IGFBP3 and MAPK/ERK signaling mediates melatonin-induced antitumor activity in prostate cancer. Journal of pineal research.Jan 2017;62(1).

McKay R. Sequential Testosterone and Enzalutamide Prevents Unfavorable Progression. Identifier: NCT04363164. Updated 10/31/2023. Accessed 3/11/2024.

McLarty J, Bigelow RL, Smith M, Elmajian D, Ankem M, Cardelli JA. Tea polyphenols decrease serum levels of prostate-specific antigen, hepatocyte growth factor, and vascular endothelial growth factor in prostate cancer patients and inhibit production of hepatocyte growth factor and vascular endothelial growth factor in vitro. Cancer prevention research (Philadelphia, Pa.). Jul 2009;2(7):673-682.

McLeod DG. Success and failure of single-modality treatment for early prostate cancer. Rev Urol.2004;6 Suppl 2:S13-19.

McMahon GC, Brown GA, Mueller TJ. Utilization of individualized prostate cancer and genomic biomarkers for the practicing urologist. Rev Urol. 2017;19(2):97-105.

Meani D, Solarić M, Visapää H, Rosén RM, Janknegt R, Soče M. Practical differences between luteinizing hormone-releasing hormone agonists in prostate cancer: perspectives across the spectrum of care. Therapeutic advances in urology. 2018;10(2):51-63.

Meng X, Rosenkrantz AB, Mendhiratta N, Fenstermaker M, Huang R, Wysock JS, . . . Taneja SS. Relationship Between Prebiopsy Multiparametric Magnetic Resonance Imaging (MRI), Biopsy Indication, and MRI-ultrasound Fusion-targeted Prostate Biopsy Outcomes. Eur Urol. Mar 2016;69(3):512-517.

Metmark Genetics. [Press Release]. Metmark Receives Positive Medicare Final Coverage Decision for ProMark. 8/30/2016. Accessed 12/28/2017.

Mondul AM, Weinstein SJ, Moy KA, Mannisto S, Albanes D. Circulating 25-Hydroxyvitamin D and Prostate Cancer Survival. Cancer epidemiology, biomarkers & prevention: a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.Apr 2016;25(4):665-669.

Montgomery B, Eisenberger MA, Rettig MB, Chu F, Pili R, Stephenson JJ, . . . Taplin ME. Androgen Receptor Modulation Optimized for Response (ARMOR) Phase I and II Studies: Galeterone for the Treatment of Castration-Resistant Prostate Cancer. Clinical cancer research: an official journal of the American Association for Cancer Research.Mar 15 2016;22(6):1356-1363.

Moon DH, Efstathiou JA, Chen RC. What is the best way to radiate the prostate in 2016? Urologic oncology.Feb 2017;35(2):59-68.

Morales A, Siemens DR. Testosterone Therapy and Prostate Cancer: Incorporating Low-Level Evidence into Practical Recommendations. The Urologic clinics of North America. Nov 2022;49(4):573-582. doi:10.1016/j.ucl.2022.07.002.

Mordan-McCombs S, Brown T, Wang WL, Gaupel AC, Welsh J, Tenniswood M. Tumor progression in the LPB-Tag transgenic model of prostate cancer is altered by vitamin D receptor and serum testosterone status. The Journal of steroid biochemistry and molecular biology. Jul 2010;121(1-2):368-371.

Moreel X, Allaire J, Leger C, Caron A, Labonte ME, Lamarche B, . . . Fradet V. Prostatic and dietary omega-3 fatty acids and prostate cancer progression during active surveillance. Cancer prevention research (Philadelphia, Pa.).Jul 2014;7(7):766-776.

Morgentaler A, Caliber M. Safety of testosterone therapy in men with prostate cancer. Expert Opin Drug Saf. Nov 2019;18(11):1065-1076. doi:10.1080/14740338.2019.1666103.

Morgentaler A, Traish AM. Shifting the paradigm of testosterone and prostate cancer: the saturation model and the limits of androgen-dependent growth. Eur Urol. Feb 2009;55(2):310-20. doi:10.1016/j.eururo.2008.09.024.

Moukayed M, Grant WB. The roles of UVB and vitamin D in reducing risk of cancer incidence and mortality: A review of the epidemiology, clinical trials, and mechanisms. Reviews in endocrine & metabolic disorders.Jun 2017;18(2):167-182.

Moul JW. Hormone naive prostate cancer: predicting and maximizing response intervals. Asian journal of andrology.Nov-Dec 2015;17(6):929-935; discussion 933.

Moyer VA. Screening for prostate cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med.Jul 17 2012;157(2):120-134.

Mucci LA, Kantoff PW. Is the Evidence Sufficient to Recommend Statins for All Men With Prostate Cancer? Journal of clinical oncology: official journal of the American Society of Clinical Oncology.Oct 10 2017;35(29):3272-3274.

Nabavi N, Mahdavi SR, Ardalan MA, et al. Bipolar Androgen Therapy: When Excess Fuel Extinguishes the Fire. Biomedicines. Jul 24 2023;11(7)doi:10.3390/biomedicines11072084.

Nambiar DK, Rajamani P, Deep G, Jain AK, Agarwal R, Singh RP. Silibinin Preferentially Radiosensitizes Prostate Cancer by Inhibiting DNA Repair Signaling. Molecular cancer therapeutics.Dec 2015;14(12):2722-2734.

Nanni C, Zanoni L, Pultrone C, Schiavina R, Brunocilla E, Lodi F, . . . Fanti S. (18)F-FACBC (anti1-amino-3-(18)F-fluorocyclobutane-1-carboxylic acid) versus (11)C-choline PET/CT in prostate cancer relapse: results of a prospective trial. European journal of nuclear medicine and molecular imaging.Aug 2016;43(9):1601-1610.

National Guideline C. ACR Appropriateness Criteria: prostate cancer--pretreatment detection, surveillance, and staging. 2016.

NCCN. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Prostate Cancer. 2/21/2017a. Accessed 8/3/2017.

NCCN. National Comprehensive Cancer Network. NCCN Guidelines for Patients: Prostate Cancer. Copyright 2016a. Accessed 8/2/2017.

NCCN. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Prostate Cancer Version 2. 2017b.

NCCN. National Comprehensive Cancer Network. NCCN Guidelines for Patients: Prostate Cancer. In: Network NCC, ed. Fort Washington, PA: National Comprehensive Cancer Network Foundation; 2016b.

NCCN. National Comprehensive Cancer Network. NCCN Guidelines for Patients: Prostate Cancer. In: Network NCC, ed. Fort Washington, PA: National Comprehensive Cancer Network Foundation; 2016c.

NCI. National Cancer Institute. Radiation Therapy for Cancer. 6/30/2010. Accessed 6/1/2015.

NCI. National Cancer Institute. Prostate-Specific Antigen (PSA) Test. Last updated 10/4/2017d. Accessed 2/14/2018.

NCI. National Cancer Institute. FDA approval for abiraterone acetate. Available at Last updated 07/01/2013. Accessed 12/07/2017.

NCI. National Cancer Institute. Understanding Prostate Changes: A Health Guide for Men. Accessed 10/27/2017a.

NCI. National Cancer Institute. CAR T cells: Engineering patients' immune cells to treat their cancers. Last updated 08/31/2017b. Accessed 12/09/2017.

NCI. PDQ Prostate Cancer Prevention. Last updated 8/17/2017c.

NCI. PDQ Prostate Cancer Screening. Last updated 2/9/2018a. Accessed 2/14/2018.

NCI. PDQ Prostate Cancer Treatment. Last updated 2/6/2018b. Accessed 2/14/2018.

Nelson R. FDA Approves First HIFU Device for Prostate Tissue Ablation. Medscape. 10/22/2015. Accessed 2/15/2018.

Nelson WG, DeMarzo AM, Yegnasubramanian S. The Diet as a Cause of Human Prostate Cancer. Cancer treatment and research.2014;159:51-68.

Newsom-Davis TE, Kenny LM, Ngan S, King J, Waxman J. The promiscuous receptor. BJU Int.Nov 2009;104(9):1204-1207.

Nguyen JY, Major JM, Knott CJ, Freeman KM, Downs TM, Saxe GA. Adoption of a plant-based diet by patients with recurrent prostate cancer. Integrative cancer therapies.Sep 2006;5(3):214-223.

Nguyen PL, Haddad Z, Ross AE, Martin NE, Deheshi S, Lam LLC, . . . Klein EA. Ability of a Genomic Classifier to Predict Metastasis and Prostate Cancer-specific Mortality after Radiation or Surgery based on Needle Biopsy Specimens. Eur Urol.May 18 2017.

NLM. National Library of Medicine. Search results page. Accessed 7/14/2023.

NLM. U.S. National Library of Medicine. PubMed Health [online]. Adrenal Glands: About the Adrenal Glands. Accessed 11/29/2017.

Nordstrom T, Van Blarigan EL, Ngo V, Roy R, Weinberg V, Song X, . . . Paris PL. Associations between circulating carotenoids, genomic instability and the risk of high-grade prostate cancer. Prostate.Mar 2016;76(4):339-348.

Norris JD, Ellison SJ, Baker JG, Stagg DB, Wardell SE, Park S, . . . McDonnell DP. Androgen receptor antagonism drives cytochrome P450 17A1 inhibitor efficacy in prostate cancer. The Journal of clinical investigation.Jun 01 2017;127(6):2326-2338.

Novio S, Cartea ME, Soengas P, Freire-Garabal M, Nunez-Iglesias MJ. Effects of Brassicaceae Isothiocyanates on Prostate Cancer. Molecules.May 12 2016;21(5).

O'Shaughnessy MJ, McBride SM, Vargas HA, Touijer KA, Morris MJ, Danila DC, . . . Scher HI. A Pilot Study of a Multimodal Treatment Paradigm to Accelerate Drug Evaluations in Early-stage Metastatic Prostate Cancer. Urology.Apr 2017;102:164-172.

Onik G, Barrie K, Miessau M, Bostwick D, Vaughan D, Brady J, Budd W. Long-Term Results of Optimized Focal Therapy for Prostate Cancer: Average 10-Year Follow-Up in 70 Patients. Journal of Men's Health.2014;11(2):64-74.

Orom H, Biddle C, Underwood W, 3rd, Nelson CJ, Homish DL. What Is a "Good" Treatment Decision? Decisional Control, Knowledge, Treatment Decision Making, and Quality of Life in Men with Clinically Localized Prostate Cancer. Medical decision making: an international journal of the Society for Medical Decision Making.Aug 2016;36(6):714-725.

Ory J, Flannigan R, Lundeen C, Huang JG, Pommerville P, Goldenberg SL. Testosterone Therapy in Patients with Treated and Untreated Prostate Cancer: Impact on Oncologic Outcomes. J Urol. Oct 2016;196(4):1082-9. doi:10.1016/j.juro.2016.04.069.

Ottanelli S. Prevention and treatment of bone fragility in cancer patient. Clin Cases Miner Bone Metab. May-Aug 2015;12(2):116-129.

Packer JR, Maitland NJ. The molecular and cellular origin of human prostate cancer. Biochimica et biophysica acta.Jun 2016;1863(6 Pt A):1238-1260.

Paller CJ, Ye X, Wozniak PJ, Gillespie BK, Sieber PR, Greengold RH, . . . Carducci MA. A randomized phase II study of pomegranate extract for men with rising PSA following initial therapy for localized prostate cancer. Prostate Cancer Prostatic Dis.Mar 2013;16(1):50-55.

Pandolfi F, Franza L, Mandolini C, Conti P. Immune Modulation by Vitamin D: Special Emphasis on Its Role in Prevention and Treatment of Cancer. Clin Ther.May 2017;39(5):884-893.

Pantuck AJ, Leppert JT, Zomorodian N, Aronson W, Hong J, Barnard RJ, . . . Belldegrun A. Phase II study of pomegranate juice for men with rising prostate-specific antigen following surgery or radiation for prostate cancer. Clinical cancer research: an official journal of the American Association for Cancer Research.Jul 01 2006;12(13):4018-4026.

Parker C, Castro E, Fizazi K, et al. Prostate cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Annals of Oncology. 2020;31(9):1119-1134. doi:10.1016/j.annonc.2020.06.011

Paroni R, Terraneo L, Bonomini F, Finati E, Virgili E, Bianciardi P, . . . Samaja M. Antitumour activity of melatonin in a mouse model of human prostate cancer: relationship with hypoxia signalling. Journal of pineal research.Aug 2014;57(1):43-52.

Partin AW, W VANC, Trock BJ, Epstein JI, L VANN. CLINICAL EVALUATION OF AN EPIGENETIC ASSAY TO PREDICT MISSED CANCER IN PROSTATE BIOPSY SPECIMENS. Transactions of the American Clinical and Climatological Association.2016;127:313-327.

Patel SA, Hoffman-Censits J. Cabazitaxel in the treatment of metastatic castration-resistant prostate cancer: patient selection and special considerations. OncoTargetsand therapy.2017;10:4089-4098.

Patrikidou A, Uccello M, Tree A, Parker C, Attard G, Eeles R, . . . Reid A. Upfront Docetaxel in the Post-STAMPEDE World: Lessons from an Early Evaluation of Non-trial Usage in Hormone-Sensitive Prostate Cancer. Clinical oncology (Royal College of Radiologists (Great Britain)).Oct 2017;29(10):e174-e175.

Paur I, Lilleby W, Bohn SK, Hulander E, Klein W, Vlatkovic L, . . . Blomhoff R. Tomato-based randomized controlled trial in prostate cancer patients: Effect on PSA. Clinical nutrition (Edinburgh, Scotland).Jun 2017;36(3):672-679.

Payton S. Prostate cancer: New PSA screening guideline faces widespread opposition. Nature reviews. Urology. Jun 05 2012;9(7):351.

Pdq Integrative A, Complementary Therapies Editorial B. Prostate Cancer, Nutrition, and Dietary Supplements (PDQ(R)): Health Professional Version. PDQ Cancer Information Summaries. Bethesda (MD): National Cancer Institute (US); 2017.

Peabody JW, DeMaria LM, Tamondong-Lachica D, Florentino J, Czarina Acelajado M, Ouenes O, . . . Burgon T. Impact of a protein-based assay that predicts prostate cancer aggressiveness on urologists' recommendations for active treatment or active surveillance: a randomized clinical utility trial. BMC urology.Jul 03 2017;17(1):51.

Peisch SF, Van Blarigan EL, Chan JM, Stampfer MJ, Kenfield SA. Prostate cancer progression and mortality: a review of diet and lifestyle factors. World J Urol.Jun 2017;35(6):867-874.

Pendleton JM, Tan WW, Anai S, Chang M, Hou W, Shiverick KT, Rosser CJ. Phase II trial of isoflavone in prostate-specific antigen recurrent prostate cancer after previous local therapy. BMC cancer.May 11 2008;8:132.

Perez-Cornago A, Appleby PN, Pischon T, Tsilidis KK, Tjonneland A, Olsen A, . . . Travis RC. Tall height and obesity are associated with an increased risk of aggressive prostate cancer: results from the EPIC cohort study. BMC medicine.Jul 13 2017;15(1):115.

Perez-Cornago A, Travis RC, Appleby PN, Tsilidis KK, Tjonneland A, Olsen A, . . . Key TJ. Fruit and vegetable intake and prostate cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC). International journal of cancer. Journal international du cancer.Jul 15 2017;141(2):287-297.

Petrunak EM, Rogers SA, Aube J, Scott EE. Structural and Functional Evaluation of Clinically Relevant Inhibitors of Steroidogenic Cytochrome P450 17A1. Drug Metab Dispos.Jun 2017;45(6):635-645.

Peyromaure M, Fulla Y, Debre B, Dinh-Xuan AT. Pro PSA : a "pro cancer" form of PSA? Med Hypotheses.2005;64(1):92-95.

Pharmacutical Technology. FDA grants fast-track status for Innocrin's seviteronel to treat metastatic CRPC. Copyright 2017. Accessed 11/29/2017.

Pienta KJ, Naik H, Akhtar A, Yamazaki K, Replogle TS, Lehr J, . . . Raz A. Inhibition of spontaneous metastasis in a rat prostate cancer model by oral administration of modified citrus pectin. J Natl Cancer Inst.Mar 01 1995;87(5):348-353.

Polchert M, Voznesensky I, Soubra A, Hellstrom WJ. Updated review of testosterone replacement therapy in the setting of prostate cancer. Androgens: Clinical Research and Therapeutics. 2021;2(1):36-45.

Pollard ME, Hobbs AR, Kwon YS, Katsigeorgis M, Lavery HJ, Levinson A, . . . Jazayeri SB. Heterogeneity of Outcomes in D'Amico Intermediate-Risk Prostate Cancer Patients after Radical Prostatectomy: Influence of Primary and Secondary Gleason Score. Oncology research and treatment. 2017;40(9):508-514.

Pollock PA, Ludgate A, Wassersug RJ. In 2124, half of all men can count on developing prostate cancer. Current oncology (Toronto, Ont.).Feb 2015;22(1):10-12.

Ponholzer A, Popper N, Breitenecker F, Schmid HP, Albrecht W, Loidl W, . . . Rauchenwald M. Proposal for a standardized PSA doubling-time calculation. Anticancer research.May 2010;30(5):1633-1636.

Popovic LS, Matovina-Brko G, Popovic M. Checkpoint inhibitors in the treatment of urological malignancies. ESMO open.2017;2(2):e000165.

Porpiglia F, Manfredi M, Mele F, Cossu M, Bollito E, Veltri A, . . . De Luca S. Diagnostic Pathway with Multiparametric Magnetic Resonance Imaging Versus Standard Pathway: Results from a Randomized Prospective Study in Biopsy-naive Patients with Suspected Prostate Cancer. Eur Urol.Aug 2017;72(2):282-288.

Pounis G, Tabolacci C, Costanzo S, Cordella M, Bonaccio M, Rago L, . . . Facchiano F. Reduction by coffee consumption of prostate cancer risk: Evidence from the Moli-sani cohort and cellular models. International journal of cancer. Journal international du cancer.Jul 01 2017;141(1):72-82.

Puente J, Grande E, Medina A, Maroto P, Lainez N, Arranz JA. Docetaxel in prostate cancer: a familiar face as the new standard in a hormone-sensitive setting. Therapeutic advances in medical oncology.May 2017;9(5):307-318.

Punnen S, Pavan N, Parekh DJ. Finding the Wolf in Sheep's Clothing: The 4Kscore Is a Novel Blood Test That Can Accurately Identify the Risk of Aggressive Prostate Cancer. Rev Urol.2015;17(1):3-13.

Rabiau N, Kossai M, Braud M, Chalabi N, Satih S, Bignon YJ, Bernard-Gallon DJ. Genistein and daidzein act on a panel of genes implicated in cell cycle and angiogenesis by polymerase chain reaction arrays in human prostate cancer cell lines. Cancer epidemiology.Apr 2010;34(2):200-206.

Raffoul JJ, Banerjee S, Che M, Knoll ZE, Doerge DR, Abrams J, . . . Hillman GG. Soy isoflavones enhance radiotherapy in a metastatic prostate cancer model. International journal of cancer. Journal international du cancer.Jun 01 2007;120(11):2491-2498.

Rahbar K, Ahmadzadehfar H, Kratochwil C, Haberkorn U, Schafers M, Essler M, . . . Krause BJ. German Multicenter Study Investigating 177Lu-PSMA-617 Radioligand Therapy in Advanced Prostate Cancer Patients. J Nucl Med.Jan 2017;58(1):85-90.

Ramakrishnan Geethakumari P, Schiewer MJ, Knudsen KE, Kelly WK. PARP Inhibitors in Prostate Cancer. Current treatment options in oncology.Jun 2017;18(6):37.

Reiter RJ, Rosales-Corral SA, Tan DX, Acuna-Castroviejo D, Qin L, Yang SF, Xu K. Melatonin, a Full Service Anti-Cancer Agent: Inhibition of Initiation, Progression and Metastasis. International journal of molecular sciences. Apr 17 2017;18(4).

Ren F, Zhang S, Mitchell SH, Butler R, Young CY. Tea polyphenols down-regulate the expression of the androgen receptor in LNCaP prostate cancer cells. Oncogene.Apr 06 2000;19(15):1924-1932.

Richman EL, Carroll PR, Chan JM. Vegetable and fruit intake after diagnosis and risk of prostate cancer progression. International journal of cancer. Journal international du cancer. Jul 01 2012;131(1):201-210.

Rieken M, Shariat SF, Kluth LA, Fajkovic H, Rink M, Karakiewicz PI, . . . Pourmand G. Association of Cigarette Smoking and Smoking Cessation with Biochemical Recurrence of Prostate Cancer in Patients Treated with Radical Prostatectomy. Eur Urol.Dec 2015;68(6):949-956.

Rijnders M, de Wit R, Boormans JL, Lolkema MPJ, van der Veldt AAM. Systematic Review of Immune Checkpoint Inhibition in Urological Cancers. Eur Urol.Sep 2017;72(3):411-423.

Rivera M, Ramos Y, Rodriguez-Valentin M, Lopez-Acevedo S, Cubano LA, Zou J, . . . Boukli NM. Targeting multiple pro-apoptotic signaling pathways with curcumin in prostate cancer cells. PloS one.2017;12(6):e0179587.

Robinson K, Creed J, Reguly B, Powell C, Wittock R, Klein D, . . . Dakubo GD. Accurate prediction of repeat prostate biopsy outcomes by a mitochondrial DNA deletion assay. Prostate Cancer Prostatic Dis.Jun 2010;13(2):126-131.

Rodgers L, Peer CJ, Figg WD. Diagnosis, staging, and risk stratification in prostate cancer: Utilizing diagnostic tools to avoid unnecessary therapies and side effects. Cancer Biol Ther. May 05 2017:1-3.

Rodriguez KM, Pastuszak AW, Khera M. The Role of Testosterone Therapy in the Setting of Prostate Cancer. Curr Urol Rep. Jun 30 2018;19(8):67. doi:10.1007/s11934-018-0812-1.

Ross AE, D'Amico AV, Freedland SJ. Which, when and why? Rational use of tissue-based molecular testing in localized prostate cancer. Prostate Cancer Prostatic Dis.Mar 2016;19(1):1-6.

Roth AJ, Weinberger MI, Nelson CJ. Prostate cancer: psychosocial implications and management. Future oncology (London, England).Aug 2008;4(4):561-568.

Rothermundt C, Hayoz S, Templeton AJ, Winterhalder R, Strebel RT, Bartschi D, . . . Gillessen S. Metformin in chemotherapy-naive castration-resistant prostate cancer: a multicenter phase 2 trial (SAKK 08/09). Eur Urol.Sep 2014;66(3):468-474.

Rubio-Briones J, Casanova J, Martinez F, Dominguez-Escrig JL, Fernandez-Serra A, Dumont R, . . . Lopez-Guerrero JA. PCA3 as a second-line biomarker in a prospective controlled randomized opportunistic prostate cancer screening programme. Actas urologicas espanolas. Jun 2017;41(5):300-308.

Rundle A, Wang Y, Sadasivan S, Chitale DA, Gupta NS, Tang D, Rybicki BA. Larger men have larger prostates: Detection bias in epidemiologic studies of obesity and prostate cancer risk. Prostate.Jun 2017;77(9):949-954.

Russo GI, Regis F, Castelli T, Favilla V, Privitera S, Giardina R, . . . Morgia G. A Systematic Review and Meta-analysis of the Diagnostic Accuracy of Prostate Health Index and 4-Kallikrein Panel Score in Predicting Overall and High-grade Prostate Cancer. Clinical genitourinary cancer. Aug 2017;15(4):429-439.e421.

Ruxton C. Health benefits of omega-3 fatty acids. Nursing standard (Royal College of Nursing (Great Britain): 1987).Aug 11-17 2004;18(48):38-42.

Rycaj K, Li H, Zhou J, Chen X, Tang DG. Cellular determinants and microenvironmental regulation of prostate cancer metastasis. Semin Cancer Biol.Jun 2017;44:83-97.

Saad F. Optimizing bone health in prostate cancer. Accessed March 10, 2021, 2021.

Saini S. PSA and beyond: alternative prostate cancer biomarkers. Cellular oncology (Dordrecht).Apr 2016;39(2):97-106.

Salman JW, Schoots IG, Carlsson SV, Jenster G, Roobol MJ. Prostate Specific Antigen as a Tumor Marker in Prostate Cancer: Biochemical and Clinical Aspects. Advances in experimental medicine and biology.2015;867:93-114.

Sanda MG, Feng Z, Howard DH, Tomlins SA, Sokoll LJ, Chan DW, . . . Taneja S. Association Between Combined TMPRSS2:ERG and PCA3 RNA Urinary Testing and Detection of Aggressive Prostate Cancer. JAMA Oncol.May 18 2017.

Sarkar RR, Patel SH, Parsons JK, et al. Testosterone therapy does not increase the risks of prostate cancer recurrence or death after definitive treatment for localized disease. Prostate cancer and prostatic diseases. Dec 2020;23(4):689-695. doi:10.1038/s41391-020-0241-3.

Sarmento-Cabral A, F LL, Gahete MD, Castano JP, Luque RM. Metformin Reduces Prostate Tumor Growth, in a Diet-Dependent Manner, by Modulating Multiple Signaling Pathways. Mol Cancer Res.Jul 2017;15(7):862-874.

Sartippour MR, Seeram NP, Rao JY, Moro A, Harris DM, Henning SM, . . . Heber D. Ellagitannin-rich pomegranate extract inhibits angiogenesis in prostate cancer in vitro and in vivo. International journal of oncology.Feb 2008;32(2):475-480.

Sartor O, Coleman R, Nilsson S, Heinrich D, Helle SI, O'Sullivan JM, . . . Parker C. Effect of radium-223 dichloride on symptomatic skeletal events in patients with castration-resistant prostate cancer and bone metastases: results from a phase 3, double-blind, randomised trial. The Lancet. Oncology.Jun 2014;15(7):738-746.

Sartori DA, Chan DW. Biomarkers in prostate cancer: what's new? Current opinion in oncology.May 2014;26(3):259-264.

Sato N, Shiota M, Shiga KI, Takeuchi A, Inokuchi J, Tatsugami K, . . . Eto M. Smoking effect on oncological outcome among men with prostate cancer after radical prostatectomy. Japanese journal of clinical oncology.May 01 2017;47(5):453-457.

Saxe GA, Hebert JR, Carmody JF, Kabat-Zinn J, Rosenzweig PH, Jarzobski D, . . . Blute RD. Can diet in conjunction with stress reduction affect the rate of increase in prostate specific antigen after biochemical recurrence of prostate cancer? J Urol.Dec 2001;166(6):2202-2207.

Sayour EJ, Mitchell DA. Manipulation of Innate and Adaptive Immunity through Cancer Vaccines. J Immunol Res.2017;2017:3145742.

Schepisi G, Farolfi A, Conteduca V, Martignano F, De Lisi D, Ravaglia G, . . . De Giorgi U. Immunotherapy for Prostate Cancer: Where We Are Headed. International journal of molecular sciences. Dec 5 2017;18(12).

Scherr KA, Fagerlin A, Hofer T, Scherer LD, Holmes-Rovner M, Williamson LD, . . . Ubel PA. Physician Recommendations Trump Patient Preferences in Prostate Cancer Treatment Decisions. Medical decision making: an international journal of the Society for Medical Decision Making.Jan 2017;37(1):56-69.

Schjenken JE, Robertson SA. Seminal Fluid Signalling in the Female Reproductive Tract: Implications for Reproductive Success and Offspring Health. Advances in experimental medicine and biology.2015;868:127-158.

Schnoeller TJ, Jentzmik F, Schrader AJ, Steinestel J. Influence of serum cholesterol level and statin treatment on prostate cancer aggressiveness. Oncotarget.Apr 07 2017.

Seeram NP, Aronson WJ, Zhang Y, Henning SM, Moro A, Lee RP, . . . Heber D. Pomegranate ellagitannin-derived metabolites inhibit prostate cancer growth and localize to the mouse prostate gland. Journal of agricultural and food chemistry.Sep 19 2007;55(19):7732-7737.

Siddiqui IA, Asim M, Hafeez BB, Adhami VM, Tarapore RS, Mukhtar H. Green tea polyphenol EGCG blunts androgen receptor function in prostate cancer. FASEB journal: official publication of the Federation of American Societies for Experimental Biology.Apr 2011;25(4):1198-1207.

Siegel AB, Narayan R, Rodriguez R, Goyal A, Jacobson JS, Kelly K, . . . Greenlee H. A phase I dose-finding study of silybin phosphatidylcholine (milk thistle) in patients with advanced hepatocellular carcinoma. Integrative cancer therapies.Jan 2014;13(1):46-53.

Silvestri I, Cattarino S, Giantulli S, Nazzari C, Collalti G, Sciarra A. A Perspective of Immunotherapy for Prostate Cancer. Cancers.Jul 07 2016;8(7).

Singh-Gupta V, Zhang H, Yunker CK, Ahmad Z, Zwier D, Sarkar FH, Hillman GG. Daidzein effect on hormone refractory prostate cancer in vitro and in vivo compared to genistein and soy extract: potentiation of radiotherapy. Pharmaceutical research.Jun 2010;27(6):1115-1127.

Siu SW, Lau KW, Tam PC, Shiu SY. Melatonin and prostate cancer cell proliferation: interplay with castration, epidermal growth factor, and androgen sensitivity. Prostate.Jul 01 2002;52(2):106-122.

Slager SL, Schaid DJ, Cunningham JM, McDonnell SK, Marks AF, Peterson BJ, . . . Thibodeau SN. Confirmation of linkage of prostate cancer aggressiveness with chromosome 19q. Am J Hum Genet.Mar 2003;72(3):759-762.

Small EJ. Prostate Cancer. In: Goldman LS, A.I., ed. Goldman-Cecil Medicine. Philadelphia: Elsevier Health Sciences; 2015.

Small EJ, Schellhammer PF, Higano CS, Redfern CH, Nemunaitis JJ, Valone FH, . . . Hershberg RM. Placebo-controlled phase III trial of immunologic therapy with sipuleucel-T (APC8015) in patients with metastatic, asymptomatic hormone refractory prostate cancer. Journal of clinical oncology: official journal of the American Society of Clinical Oncology.Jul 01 2006;24(19):3089-3094.

Smith CJ, Dorsey TH, Tang W, Jordan SV, Loffredo CA, Ambs S. Aspirin Use Reduces the Risk of Aggressive Prostate Cancer and Disease Recurrence in African-American Men. Cancer epidemiology, biomarkers & prevention: a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. Jun 2017;26(6):845-853.

Smith MR, Antonarakis ES, Ryan CJ, Berry WR, Shore ND, Liu G, . . . Rathkopf DE. Phase 2 Study of the Safety and Antitumor Activity of Apalutamide (ARN-509), a Potent Androgen Receptor Antagonist, in the High-risk Nonmetastatic Castration-resistant Prostate Cancer Cohort. Eur Urol.Dec 2016;70(6):963-970.

Smith MR, Hussain M, Saad F, et al. Darolutamide and Survival in Metastatic, Hormone-Sensitive Prostate Cancer. New England Journal of Medicine. 2022;doi:10.1056/NEJMoa2119115

Smith MR, Saad F, Chowdhury S, et al. Apalutamide Treatment and Metastasis-free Survival in Prostate Cancer. The New England journal of medicine. Apr 12 2018;378(15):1408-1418. doi:10.1056/NEJMoa1715546

Sobota AE. Inhibition of bacterial adherence by cranberry juice: potential use for the treatment of urinary tract infections. J Urol.May 1984;131(5):1013-1016.

Spencer L, Mann C, Metcalfe M, Webb M, Pollard C, Spencer D, . . . Dennison A. The effect of omega-3 FAs on tumour angiogenesis and their therapeutic potential. European journal of cancer (Oxford, England: 1990).Aug 2009;45(12):2077-2086.

Spratt DE, Yousefi K, Deheshi S, Ross AE, Den RB, Schaeffer EM, . . . Feng FY. Individual Patient-Level Meta-Analysis of the Performance of the Decipher Genomic Classifier in High-Risk Men After Prostatectomy to Predict Development of Metastatic Disease. Journal of clinical oncology: official journal of the American Society of Clinical Oncology.Jun 20 2017;35(18):1991-1998.

Srinivas S, Feldman D. A phase II trial of calcitriol and naproxen in recurrent prostate cancer. Anticancer research.Sep 2009;29(9):3605-3610.

Stattin P, Vickers AJ, Sjoberg DD, Johansson R, Granfors T, Johansson M, . . . Lilja H. Improving the Specificity of Screening for Lethal Prostate Cancer Using Prostate-specific Antigen and a Panel of Kallikrein Markers: A Nested Case-Control Study. Eur Urol.Aug 2015;68(2):207-213.

Steinberger E, Kollmeier M, McBride S, Novak C, Pei X, Zelefsky MJ. Cigarette smoking during external beam radiation therapy for prostate cancer is associated with an increased risk of prostate cancer-specific mortality and treatment-related toxicity. BJU Int.Oct 2015;116(4):596-603.

Stewart GD, Van Neste L, Delvenne P, Delree P, Delga A, McNeill SA, . . . Harrison DJ. Clinical utility of an epigenetic assay to detect occult prostate cancer in histopathologically negative biopsies: results of the MATLOC study. J Urol.Mar 2013;189(3):1110-1116.

Stish BJ, Davis BJ, Mynderse LA, Deufel CL, Choo R. Brachytherapy in the Management of Prostate Cancer. Surgical oncology clinics of North America.Jul 2017;26(3):491-513.

Stone L. Prostate cancer: Light, camera, action - photodynamic therapy for low-risk disease. Nature reviews. Urology. Mar 2017;14(3):134.

Story EN, Kopec RE, Schwartz SJ, Harris GK. An update on the health effects of tomato lycopene. Annual review of food science and technology.2010;1:189-210.

Strittmatter F, Stieber P, Nagel D, Fullhase C, Walther S, Stief CG, Waidelich R. Detection of prostate cancer with complexed PSA and complexed/total PSA ratio - is there any advantage? European journal of medical research.Oct 10 2011;16(10):445-450.

Student V, Vidlar A, Bouchal J, Vrbkova J, Kolar Z, Kral M, . . . Vostalova J. Cranberry intervention in patients with prostate cancer prior to radical prostatectomy. Clinical, pathological and laboratory findings. Biomedical papers of the Medical Faculty of the University Palacky, Olomouc, Czechoslovakia.Dec 2016;160(4):559-565.

Swami S, Krishnan AV, Moreno J, Bhattacharyya RS, Gardner C, Brooks JD, . . . Feldman D. Inhibition of prostaglandin synthesis and actions by genistein in human prostate cancer cells and by soy isoflavones in prostate cancer patients. International journal of cancer. Journal international du cancer.May 01 2009;124(9):2050-2059.

Sweeney CJ, Chen YH, Carducci M, Liu G, Jarrard DF, Eisenberger M, . . . DiPaola RS. Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer. N Engl J Med. Aug 20 2015;373(8):737-746.

Taaffe DR, Newton RU, Spry N, Joseph D, Chambers SK, Gardiner RA, . . . Galvao DA. Effects of Different Exercise Modalities on Fatigue in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy: A Year-long Randomised Controlled Trial. Eur Urol.Aug 2017;72(2):293-299.

Tabayoyong W, Abouassaly R. Prostate Cancer Screening and the Associated Controversy. The Surgical clinics of North America.Oct 2015;95(5):1023-1039.

Taborelli M, Polesel J, Parpinel M, Stocco C, Birri S, Serraino D, Zucchetto A. Fruit and vegetables consumption is directly associated to survival after prostate cancer. Mol Nutr Food Res. Apr 2017;61(4).

Tai SY, Huang SP, Bao BY, Wu MT. Urinary melatonin-sulfate/cortisol ratio and the presence of prostate cancer: A case-control study. Sci Rep.Jul 08 2016;6:29606.

Takagi M, Demizu Y, Terashima K, Fujii O, Jin D, Niwa Y, . . . Okimoto T. Long-term outcomes in patients treated with proton therapy for localized prostate cancer. Cancer Med.Sep 06 2017.

Tang B, Han CT, Gan HL, Zhang GM, Zhang CZ, Yang WY, . . . Ye DW. Smoking increased the risk of prostate cancer with grade group >/= 4 and intraductal carcinoma in a prospective biopsy cohort. Prostate.Jun 2017;77(9):984-989.

Teply BA, Antonarakis ES. Novel mechanism-based therapeutics for androgen axis blockade in castration-resistant prostate cancer. Curr Opin Endocrinol Diabetes Obes.Jun 2016;23(3):279-290.

Terada N, Akamatsu S, Kobayashi T, Inoue T, Ogawa O, Antonarakis ES. Prognostic and predictive biomarkers in prostate cancer: latest evidence and clinical implications. Therapeutic advances in medical oncology.Aug 2017;9(8):565-573.

Thompson IM, Pauler DK, Goodman PJ, Tangen CM, Lucia MS, Parnes HL, . . . Coltman CA, Jr. Prevalence of prostate cancer among men with a prostate-specific antigen level < or =4.0 ng per milliliter. N Engl J Med.May 27 2004;350(22):2239-2246.

Thomsen FB, Sandin F, Garmo H, Lissbrant IF, Ahlgren G, Van Hemelrijck M, . . . Stattin P. Gonadotropin-releasing Hormone Agonists, Orchiectomy, and Risk of Cardiovascular Disease: Semi-ecologic, Nationwide, Population-based Study. Eur Urol.Jul 12 2017.

Thysell E, Surowiec I, Hornberg E, Crnalic S, Widmark A, Johansson AI, . . . Wikstrom P. Metabolomic characterization of human prostate cancer bone metastases reveals increased levels of cholesterol. PloS one.Dec 03 2010;5(12):e14175.

Tosoian JJ, Chappidi MR, Bishoff JT, Freedland SJ, Reid J, Brawer M, . . . Ross AE. Prognostic utility of biopsy-derived cell cycle progression score in patients with National Comprehensive Cancer Network low-risk prostate cancer undergoing radical prostatectomy: implications for treatment guidance. BJU Int.May 08 2017.

Tosoian JJ, Druskin SC, Andreas D, Mullane P, Chappidi M, Joo S, . . . Ross AE. Use of the Prostate Health Index for detection of prostate cancer: results from a large academic practice. Prostate Cancer Prostatic Dis.Jun 2017;20(2):228-233.

Tosoian JJ, Loeb S. Radical retropubic prostatectomy: comparison of the open and robotic approaches for treatment of prostate cancer. Rev Urol.2012;14(1-2):20-27.

Traboulsi SL, Saad F. The role of bone-targeted therapies for prostate cancer in 2017. Current opinion in supportive and palliative care.Sep 2017;11(3):216-224.

Tran HN, Li Y, Udaltsova N, Armstrong MA, Friedman GD, Klatsky AL. Risk of cancer in Asian Americans: a Kaiser Permanente cohort study. Cancer Causes Control.Oct 2016;27(10):1197-1207.

Twardowski P, Atkinson S, Boldt-Houle D, Sartor AO. Late dosing of luteinizing hormone-releasing hormone agonists (LHRH) and testosterone (T) levels >20 ng/dL in prostate cancer (PCa). Journal of Clinical Oncology. 2020;38(6_suppl):31-31.

Uemura H, Arai G, Uemura H, et al. Safety and efficacy of apalutamide in Japanese patients with metastatic castration-sensitive prostate cancer receiving androgen deprivation therapy: Final report for the Japanese subpopulation analysis of the randomized, placebo-controlled, phase III TITAN study. Int J Urol. Mar 15 2022;doi:10.1111/iju.14843

USPSTF. Draft Recommendation Statement: Prostate Cancer. Screening 4/2017. Accessed 8/22/2017.

USPSTF. Screening for prostate cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med.Aug 05 2008;149(3):185-191.

Vaidyanathan R, Mishra VC. Chronic prostatitis: Current concepts. Indian journal of urology: IJU:journal of the Urological Society of India.Jan 2008;24(1):22-27.

Vaknin Y, Hadas R, Schafferman D, Murkhovsky L, Bashan N. The potential of milk thistle (Silybum marianum L.), an Israeli native, as a source of edible sprouts rich in antioxidants. International journal of food sciences and nutrition.Jun 2008;59(4):339-346.

Van Neste L, Hendriks RJ, Dijkstra S, Trooskens G, Cornel EB, Jannink SA, . . . Schalken JA. Detection of High-grade Prostate Cancer Using a Urinary Molecular Biomarker-Based Risk Score. Eur Urol.Nov 2016;70(5):740-748.

Vazquez-Salas RA, Torres-Sanchez L, Lopez-Carrillo L, Romero-Martinez M, Manzanilla-Garcia HA, Cruz-Ortiz CH, . . . Moreno-Alcazar O. History of gonorrhea and prostate cancer in a population-based case-control study in Mexico. Cancer epidemiology.Feb 2016;40:95-101.

Vickers AJ, Thompson IM, Klein E, Carroll PR, Scardino PT. A commentary on PSA velocity and doubling time for clinical decisions in prostate cancer. Urology.Mar 2014;83(3):592-596.

Vidal AC, Freedland SJ. Obesity and Prostate Cancer: A Focused Update on Active Surveillance, Race, and Molecular Subtyping. Eur Urol.Jul 2017;72(1):78-83.

Vieweg J. Immunotherapy for advanced prostate cancer. Rev Urol.2007;9 Suppl 1:S29-38.

Virgo KS, Basch E, Loblaw DA, Oliver TK, Rumble RB, Carducci MA, . . . Singer EA. Second-Line Hormonal Therapy for Men With Chemotherapy-Naive, Castration-Resistant Prostate Cancer: American Society of Clinical Oncology Provisional Clinical Opinion. Journal of clinical oncology: official journal of the American Society of Clinical Oncology.Jun 10 2017;35(17):1952-1964.

Voltaggio L, Cimino-Mathews A, Bishop JA, Argani P, Cuda JD, Epstein JI, . . . Montgomery EA. Current concepts in the diagnosis and pathobiology of intraepithelial neoplasia: A review by organ system. CA: a cancer journal for clinicians.Sep 2016;66(5):408-436.

Vue B, Chen QH. The Potential of Flavonolignans in Prostate Cancer Management. Current medicinal chemistry.2016;23(34):3925-3950.

Vue B, Zhang X, Lee T, Nair N, Zhang S, Chen G, . . . Chen QH. 5- or/and 20-O-alkyl-2,3-dehydrosilybins: Synthesis and biological profiles on prostate cancer cell models. Bioorganic & medicinal chemistry.Sep 01 2017;25(17):4845-4854.

Wadosky KM, Koochekpour S. Therapeutic Rationales, Progresses, Failures, and Future Directions for Advanced Prostate Cancer. International journal of biological sciences. 2016;12(4):409-426.

Wagner D, Trudel D, Van der Kwast T, Nonn L, Giangreco AA, Li D, . . . Vieth R. Randomized clinical trial of vitamin D3 doses on prostatic vitamin D metabolite levels and ki67 labeling in prostate cancer patients. The Journal of clinical endocrinology and metabolism.Apr 2013;98(4):1498-1507.

Wallis CJD, Glaser A, Hu JC, Huland H, Lawrentschuk N, Moon D, . . . Nam RK. Survival and Complications Following Surgery and Radiation for Localized Prostate Cancer: An International Collaborative Review. Eur Urol.Jun 10 2017.

Walz S, Maas M, Stenzl A, Todenhofer T. Bone Health Issues in Patients with Prostate Cancer: An Evidence-Based Review. World J Mens Health. Apr 2020;38(2):151-163. doi:10.5534/wjmh.190044

Wang A, Wang S, Zhu C, Huang H, Wu L, Wan X, . . . Zhao H. Coffee and cancer risk: A meta-analysis of prospective observational studies. Sci Rep.Sep 26 2016;6:33711.

Wang FB, Chen R, Ren SC, Shi XL, Zhu YS, Zhang W, . . . Sun YH. Prostate cancer antigen 3 moderately improves diagnostic accuracy in Chinese patients undergoing first prostate biopsy. Asian journal of andrology.Mar-Apr 2017;19(2):238-243.

Wang J, Eltoum IE, Lamartiniere CA. Genistein alters growth factor signaling in transgenic prostate model (TRAMP). Molecular and cellular endocrinology.Apr 30 2004;219(1-2):171-180.

Wang Q, Li YF, Jiang J, Zhang Y, Liu XD, Li K. The establishment and evaluation of a new model for the prediction of prostate cancer. Medicine.Mar 2017;96(11):e6138.

Wang YC, Chung CH, Chen JH, Chiang MH, Ti Y, Tsao CH, . . . Chang FY. Gonorrhea infection increases the risk of prostate cancer in Asian population: a nationwide population-based cohort study. European journal of clinical microbiology & infectious diseases: official publication of the European Society of Clinical Microbiology.May 2017;36(5):813-821.

Watson GW, Beaver LM, Williams DE, Dashwood RH, Ho E. Phytochemicals from Cruciferous Vegetables, Epigenetics, and Prostate Cancer Prevention. The AAPS journal.2013;15(4):951-961.

Watson MJ, George AK, Maruf M, Frye TP, Muthigi A, Kongnyuy M, . . . Pinto PA. Risk stratification of prostate cancer: integrating multiparametric MRI, nomograms and biomarkers. Future oncology (London, England). Nov 2016;12(21):2417-2430.

Weh KM, Clarke J, Kresty LA. Cranberries and Cancer: An Update of Preclinical Studies Evaluating the Cancer Inhibitory Potential of Cranberry and Cranberry Derived Constituents. Antioxidants (Basel, Switzerland).Aug 18 2016;5(3).

Weiner AB, Matulewicz RS, Schaeffer EM, Liauw SL, Feinglass JM, Eggener SE. Contemporary management of men with high-risk localized prostate cancer in the United States. Prostate Cancer Prostatic Dis.Jun 20 2017.

Wells TS, Bukowinski AT, Smith TC, Smith B, Dennis LK, Chu LK, . . . Ryan MA. Racial differences in prostate cancer risk remain among US servicemen with equal access to care. Prostate.May 15 2010;70(7):727-734.

Whitburn J, Edwards CM, Sooriakumaran P. Metformin and Prostate Cancer: a New Role for an Old Drug. Current urology reports.Jun 2017;18(6):46.

Wilczynski CA, L. Testosterone effects on the prostate gland: Review of the pathophysiology and considerations in prostate cancer. J Fam Med Dis Prev.2015;1(004).

Wilson KM, Kasperzyk JL, Rider JR, Kenfield S, van Dam RM, Stampfer MJ, . . . Mucci LA. Coffee consumption and prostate cancer risk and progression in the Health Professionals Follow-up Study. J Natl Cancer Inst.Jun 08 2011;103(11):876-884.

Wilson KM, Mucci LA, Drake BF, Preston MA, Stampfer MJ, Giovannucci E, Kibel AS. Meat, Fish, Poultry, and Egg Intake at Diagnosis and Risk of Prostate Cancer Progression. Cancer prevention research (Philadelphia, Pa.).Dec 2016;9(12):933-941.

Wilt TJ, Dahm P. PSA Screening for Prostate Cancer: Why Saying No is a High-Value Health Care Choice. Journal of the National Comprehensive Cancer Network: JNCCN.Dec 2015;13(12):1566-1574.

Wilt TJ, Jones KM, Barry MJ, Andriole GL, Culkin D, Wheeler T, . . . Brawer MK. Follow-up of Prostatectomy versus Observation for Early Prostate Cancer. The New England journal of medicine.Jul 13 2017;377(2):132-142.

Wojno KJ, Costa FJ, Cornell RJ, Small JD, Pasin E, Van Criekinge W, . . . Van Neste L. Reduced Rate of Repeated Prostate Biopsies Observed in ConfirmMDx Clinical Utility Field Study. American health & drug benefits.May 2014;7(3):129-134.

Wolf F, Gaisberger C, Ziegler I, Krenn E, Scherer P, Hruby S, . . . Sedlmayer F. Comparison of two different rectal spacers in prostate cancer external beam radiotherapy in terms of rectal sparing and volume consistency. Radiother Oncol.Aug 2015;116(2):221-225.

Woodrum DA, Kawashima A, Gorny KR, Mynderse LA. Prostate cancer: state of the art imaging and focal treatment. Clinical radiology.Aug 2017;72(8):665-679.

Wright JL, Salinas CA, Lin DW, Kolb S, Koopmeiners J, Feng Z, Stanford JL. Prostate cancer specific mortality and Gleason 7 disease differences in prostate cancer outcomes between cases with Gleason 4 + 3 and Gleason 3 + 4 tumors in a population based cohort. J Urol.Dec 2009;182(6):2702-2707.

Wu Y, Wang Y, Gu Y, et al. Prostate Cancer Risk and Prognostic Influence Among Users of 5-Alpha-Reductase Inhibitors and Alpha-Blockers: A Systematic Review and Meta-Analysis. Urology. 2020; 145, 216-223.

Xi SC, Siu SW, Fong SW, Shiu SY. Inhibition of androgen-sensitive LNCaP prostate cancer growth in vivo by melatonin: association of antiproliferative action of the pineal hormone with mt1 receptor protein expression. Prostate.Jan 01 2001;46(1):52-61.

Xie B, Zhang G, Wang X, Xu X. Body mass index and incidence of nonaggressive and aggressive prostate cancer: a dose-response meta-analysis of cohort studies. Oncotarget.Nov 14 2017;8(57):97584-97592.

Xie DD, Chen YH, Xu S, Zhang C, Wang DM, Wang H, . . . Yu DX. Low vitamin D status is associated with inflammation in patients with prostate cancer. Oncotarget.Mar 28 2017;8(13):22076-22085.

Xu J, Janisse J, Ruterbusch JJ, Ager J, Liu J, Holmes-Rovner M, Schwartz KL. Patients' Survival Expectations With and Without Their Chosen Treatment for Prostate Cancer. Annals of family medicine.May 2016;14(3):208-214.

Yan J, Katz A. PectaSol-C modified citrus pectin induces apoptosis and inhibition of proliferation in human and mouse androgen-dependent and- independent prostate cancer cells. Integrative cancer therapies.Jun 2010;9(2):197-203.

Yoshimura K, Minami T, Nozawa M, Kimura T, Egawa S, Fujimoto H, . . . Uemura H. A Phase 2 Randomized Controlled Trial of Personalized Peptide Vaccine Immunotherapy with Low-dose Dexamethasone Versus Dexamethasone Alone in Chemotherapy-naive Castration-resistant Prostate Cancer. Eur Urol.Jul 2016;70(1):35-41.

You X, Huang S, Wang X, et al. Efficacy and safety of bipolar androgen therapy in castration-resistant prostate cancer following abiraterone or enzalutamide resistance: A systematic review. Frontiers in endocrinology. 2022;13:1125838. doi:10.3389/fendo.2022.1125838.

Yu S, Jiang Y, Wan F, Wu J, Gao Z, Liu D. Immortalized Cancer-associated Fibroblasts Promote Prostate Cancer Carcinogenesis, Proliferation and Invasion. Anticancer research.Aug 2017;37(8):4311-4318.

Yunfeng G, Weiyang H, Xueyang H, Yilong H, Xin G. Exercise overcome adverse effects among prostate cancer patients receiving androgen deprivation therapy: An update meta-analysis. Medicine.Jul 2017;96(27):e7368.

Zappala SM, Dong Y, Linder V, Reeve M, Sjoberg DD, Mathur V, . . . Steiner M. The 4Kscore blood test accurately identifies men with aggressive prostate cancer prior to prostate biopsy with or without DRE information. International journal of clinical practice.Jun 2017;71(6).

Zardawi I, Chong P. Metastatic Prostate Cancer to the Urethra Masquerading as Urothelial Carcinoma. Urology case reports. Jul 2016;7:33-36.

Zhang H, Messing EM, Travis LB, Hyrien O, Chen R, Milano MT, Chen Y. Age and Racial Differences among PSA-Detected (AJCC Stage T1cN0M0) Prostate Cancer in the U.S.: A Population-Based Study of 70,345 Men. Frontiers in oncology.2013;3:312.

Zhang S, Hu H, Wang L, Liu F, Pan S. Preparation and prebiotic potential of pectin oligosaccharides obtained from citrus peel pectin. Food chemistry.Apr 1 2018;244:232-237.

Zhang T, Zhang L, Zhang T, Fan J, Wu K, Guan Z, . . . Guo P. Metformin sensitizes prostate cancer cells to radiation through EGFR/p-DNA-PKCS in vitro and in vivo. Radiation research.Jun 2014;181(6):641-649.

Zhou CK, Daugherty SE, Liao LM, Freedman ND, Abnet CC, Pfeiffer R, Cook MB. Do Aspirin and Other NSAIDs Confer a Survival Benefit in Men Diagnosed with Prostate Cancer? A Pooled Analysis of NIH-AARP and PLCO Cohorts. Cancer prevention research (Philadelphia, Pa.).Jul 2017;10(7):410-420.

Zu K, Mucci L, Rosner BA, Clinton SK, Loda M, Stampfer MJ, Giovannucci E. Dietary lycopene, angiogenesis, and prostate cancer: a prospective study in the prostate-specific antigen era. J Natl Cancer Inst.Feb 2014;106(2):djt430.

Zuccolotto G, Fracasso G, Merlo A, Montagner IM, Rondina M, Bobisse S, . . . Rosato A. PSMA-specific CAR-engineered T cells eradicate disseminated prostate cancer in preclinical models. PloS one.2014;9(10):e109427.