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Prostate Cancer, Magnesium, and Vitamin C Topical

June 2016

By Life Extension

Prostate Cancer

The Melbourne Consensus Statement on the early detection of prostate cancer.

Various conflicting guidelines and recommendations about prostate cancer screening and early detection have left both clinicians and their patients quite confused. At the Prostate Cancer World Congress held in Melbourne in August 2013, a multidisciplinary group of the world’s leading experts in this area gathered together and generated this set of consensus statements to bring some clarity to this confusion. The five consensus statements provide clear guidance for clinicians counselling their patients about the early detection of prostate cancer.

BJU Int. 2014 Feb;113(2):186-8

Incidence and correlates of fatigue in metastatic castration-resistant prostate cancer: a systematic review.

Prostate cancer is the second most common malignancy of men in the western countries. Fatigue is the most stressful symptom of which patients with metastatic castration-resistant prostate cancer (mCRPC) complain. The aim of this article was to report available data about the incidence of fatigue in mCRPC and its correlates. The design involved a systematic review to define incidence of fatigue according to Common Toxicity Criteria in randomized controlled trials of medical treatments of mCRPC and according to International Classification of Diseases Revision 10 (ICD-10) criteria, and to define prevalence and correlates of fatigue in patients with mCRPC. The data source used was PubMed. In December 2014, 2 PubMed searches were performed and the clinical data on the occurrence of cancer-related fatigue along the course of metastatic disease, and findings about its pathogenesis were summarized. Cancer-related fatigue, as defined according to ICD-10 criteria, was reported in 12% to 21% of patients, and prospective clinical trials showed a prevalence of Grade 3/4 fatigue according to Common Toxicity Criteria of 0% to 18%. A list of possible correlates of fatigue in mCRPC, either patient-related, disease-related, or treatment-related, is proposed herein for future studies. Antineoplastic treatments, particularly chemotherapy and radiotherapy, have a major role in the pathogenesis of fatigue in metastatic prostate cancer, however, hormonal treatments remain the most prevalent therapies. A standardized tool for multidimensional assessment of fatigue in metastatic cancer is suggested.

Clin Genitourin Cancer. 2016 Feb;14(1):5-11

Clinical, pathological and molecular prognostic factors in prostate cancer decision-making process.

Prostate cancer is the most common urologic neoplasm and the second leading cause of cancer-related death among men in many developed countries. Given the highly heterogeneous behaviour of the disease, there is a great need for prognostic factors, in order to stratify the clinical risk and give the best treatment options to the patient. Clinical factors, such as prostate-specific antigen value and derivatives, and pathological factors, such as stage and Gleason grading, are well kown prognostic factors. Nomograms can provide useful prediction in each clinical sceario. The field of molecular biomarkers is briskly evolving towards personalized medicine. TMPRSS2-ERG fusion, deletion of PTEN ed and gene panels are some of the more extensively explored molecular features in prostate cancer outcome prediction. In the near future, circulating tumour cells, exosomes and microRNAs could give us further, not invasive important tools.

Urologia. 2016 Mar 5;82(1):14-20

Overdetection in screening for prostate cancer.

PURPOSE OF REVIEW: To describe mechanisms behind and extent of overdetection in prostate cancer screening as well as possible ways to avoid unnecessary overdiagnosis. RECENT FINDINGS: Overdetection and overtreatment is common in many areas of modern medicine. Current prostate-specific antigen (PSA) testing has resulted in a marked stage shift to early stages, which, together with improvements in treatment, has resulted in a substantial decrease in prostate cancer mortality. However, nonselective, widespread PSA-testing followed by liberal biopsy criteria has resulted in a high rate of overdiagnosis, which constitutes one major obstacle to introducing population-based screening. SUMMARY: Several steps are needed to decrease overdetection: do not screen elderly men unlikely to benefit, do not biopsy without a compelling reason, differentiate screening interval according to risk, work-up benign prostate disease by using reflex tests and/or complementary biomarkers, and focus on screening men at high risk for a life-threatening disease, for example evaluate men with above-median PSA levels in midlife. Recent results indicate that use of MRI to select men for biopsy and using only lesion-directed biopsies may be one way forward. However, more studies are needed before firm recommendations can be made. When the diagnosis is made, treat only those who need treatment. Tailor treatment to tumor biology and patient characteristics, and offer active surveillance to eligible men with low-risk tumors, especially small-volume disease, as the first management.

Curr Opin Urol. 2014 May;24(3):256-63

Prostate cancer: measuring PSA.

Population screening with prostate-specific antigen (PSA) for detection of prostate cancer is a topic associated with ongoing dissent and confusion within the oncology and wider medical community. The PSA blood test has been used in various stages of prostate cancer management, including screening and the assessment of future risk of prostate cancer development, detection of recurrent disease after local therapy and in the management of advanced disease. However, PSA-based decision-making in prostate cancer has significant shortcomings. This review will summarise the evidence and current recommendations for the use of PSA in detection and management of prostate cancer.

Intern Med J. 2014 May;44(5):433-40

The memorial sloan kettering cancer center recommendations for prostate cancer screening.

The Memorial Sloan Kettering Cancer Center (MSKCC) recommendations on prostate cancer screening were developed in response to three limitations of previous screening guidelines: insufficient evidence base, failure to link screening with treatment, and lack of risk stratification. The objective of the recommendations is to provide a schema for prostate cancer screening that maximizes the benefits, in terms of reduction in prostate cancer-specific mortality, and minimizes the harms, in terms of overdiagnosis and overtreatment. We recommend the following schema for men choosing to be screened following informed decision-making: starting at age 45, prostate-specific antigen (PSA) without digital rectal examination. If PSA ≥ 3 ng/mL: consider prostate biopsy; if PSA ≥ 1 but < 3 ng/mL: return for PSA testing every 2-4 years; if PSA < 1 ng/mL: return for PSA testing at 6-10 years. PSA testing should end at age 60 for men with PSA ≤ 1 ng/ mL; at 70, unless a man is very healthy and has a higher than average PSA; at 75 for all men. The decision to biopsy a man with a PSA > 3 ng/mL should be based on a variety of factors including repeat blood draw for confirmatory testing of the PSA level, digital rectal examination results, and workup for benign disease. Additional reflex tests in blood such as a free-to-total PSA ratio, the Prostate Health Index, or 4Kscore, or urinary testing of PCA3, can also be informative in some patients. The best evidence suggests that more restricted indication for prostate biopsy and a more focused approach to pursue screening in men at highest risk of lethal cancer would retain most of the mortality benefits of aggressive screening schema, while importantly reducing harms from overdetection and overtreatment.

Urology. 2016 Feb 2

Rationale for a “male lumpectomy,” a prostate cancer targeted approach using cryoablation: results in 21 patients with at least 2 years of follow-up.

BACKGROUND: Prostate cancer in men raises many of the same issues that breast cancer does in women. Complications of prostate cancer treatment, including impotence and incontinence, affect the self-image and psyche of a man no less than does the loss of a breast in a woman. We present a pilot study in which 21 patients were treated with a focal cryoablation procedure. METHODS: Focal cryoablation was performed using biplane transrectal ultrasound if the tumor was confined to only one prostate lobe. Preoperative PSA values were recorded. Cryoablation was planned to encompass the area of known tumor. PSA values were obtained every 3 months for 2 years and every 6 months thereafter. Potency and continence status was obtained at the same intervals. Routine biopsy was obtained at 1 year. RESULTS: Twenty-one patients had focal cryoablation. Follow-up ranged from 24 to 105 months with a mean of 50 months. Twenty of 21 (95%) patients have stable PSA values with no evidence for cancer, despite 10 patients being at medium to high risk for recurrence. All patients biopsied (n = 19) were negative for tumor. Potency was maintained in 17 of 21 patients (80%). No other complications, including incontinence or fistula formation, were noted. CONCLUSION: These preliminary results indicate a “male lumpectomy,” in which the prostate tumor region itself is destroyed, appears to preserve potency in a majority of patients and limits other complications, without compromising cancer control. If these results are confirmed by further studies and long-term follow-up, this treatment approach could have a profound effect on prostate cancer management.

Cardiovasc Intervent Radiol. 2008 Jan-Feb; 31(1):98-106

“Male lumpectomy”: focal therapy for prostate cancer using cryoablation.

The introduction of breast-sparing surgery (ie, “lumpectomy”) revolutionized the management of breast cancer. The use of lumpectomy showed that quality of life could be optimized without compromising treatment efficacy. Complications of prostate cancer treatment, including impotence and incontinence, adversely alter the male self-image similarly to the way the loss of a breast does for a woman. Traditional thinking holds that prostate cancer is multifocal and therefore is not amenable to focal treatment. However, histopathologic findings from published data have indicated that up to 25% of prostate cancers are solitary and unilateral. Furthermore, the significance of minute secondary cancers might be minimal. These observations raise the question of whether certain patients can be identified and treated with a limited “lumpectomy.” In this study, focal cryoablation has been used to ablate the area of known cancer as determined by staging biopsies. The serum prostate-specific antigen (PSA) concentration was obtained every 3 months for 2 years and every 6 months thereafter. American Society for Therapeutic Radiology Oncology (ASTRO) criteria for PSA recurrence were used. A total of 55 patients with > or = 1 year of follow-up had undergone focal cryoablation. Follow-up ranged from 1 to 10 years (mean, 3.6 years). At the original transrectal ultrasound biopsy, the mean and median numbers of cores taken were 9.9 and 10 (SD, +/- 3.5), respectively. Mean and median numbers of positive cores were 1.8 and 1 (SD, +/- 1.3), respectively. Of the 55 study patients, 52 (95%) had stable PSA levels with no evidence of cancer despite a medium to high risk for recurrence in 29 patients. All biopsy findings were negative among the 26 patients with a stable PSA level who had undergone routine biopsy at 1 year. No local recurrence was noted in treated areas. Potency was maintained in 44 (86%) of 51 patients. Of the 54 patients without previous prostate surgery or radiotherapy, all were continent. These preliminary results indicate that “male lumpectomy”—in which the prostate tumor region itself is destroyed—preserves potency in most patients and limits other complications (particularly incontinence) without compromising cancer control. Additional studies and long-term follow-up are needed to confirm that this treatment approach could have a profound effect on prostate cancer management.

Urology. 2007 Dec;70(6 Suppl):16-21

The “male lumpectomy”: focal therapy for prostate cancer using cryoablation results in 48 patients with at least 2-year follow-up.

BACKGROUND: The use of breast sparing surgery, i.e., “lumpectomy”, revolutionized management of breast cancer. Lumpectomy confirmed that quality of life issues can successfully be addressed without compromising treatment efficacy. Complications of prostate cancer treatment, including impotence and incontinence, affect the male self image no less than the loss of a breast does a woman. Traditional thinking held that prostate cancer was multifocal and therefore not amenable to a focal treatment approach. Recent pathology literature indicates, however, that up to 25% of prostate cancers are solitary and unilateral. This raises the question of whether these patients can be identified and treated with a limited “lumpectomy” or focal cancer treatment. METHODS: Focal cryoablation was planned to encompass the area of known tumor based on staging biopsies. PSAs were obtained every 3 months for 2 years and then every 6 months thereafter. RESULTS: Forty-eight patients with at least 2-year follow-up had focal cryoablation. Follow-up ranged from 2 years 10 years with a mean of 4.5 years; 45 of 48 patients (94%) have stable PSAs [American Society of Therapeutic Radiology and Oncology (ASTRO) criteria] with no evidence for cancer, despite 25 patients being medium to high risk for recurrence. Of the 24 patients with stable PSAs who were routinely biopsied (n = 24) all were negative. No local recurrences were noted in areas treated. Potency was maintained to the satisfaction of the patient in of 36 of 40 patients who were potent preoperatively. Of the 48, all were continent. CONCLUSION: These preliminary results indicate a “male lumpectomy” in which the prostate tumor region itself is destroyed, appears to preserve potency in a majority of patients and limits other complications (particularly incontinence), without compromising cancer control. If confirmed by further studies and long-term follow-up, this treatment approach could have a profound effect on prostate cancer management.

Urol Onco l. 2008 Sep-Oct;26(5):500-5

Three-dimensional prostate mapping biopsy has a potentially significant impact on prostate cancer management.

PURPOSE: To compare a new staging, three-dimensional prostate mapping biopsy (3D-PMB) method with traditional transrectal ultrasound (TRUS) biopsy and assess its possible impact on patient management. PATIENTS AND METHODS: One hundred eighty patients with unilateral cancer on TRUS biopsy, who were considering conservative management, underwent restaging with 3D-PMB. The 3D-PMB was carried out transperineally using a brachytherapy grid under TRUS guidance. Biopsies were taken every 5 mm throughout the volume of the prostate, and labeling of the specimen coordinates allowed accurate reconstruction of the location and extent of a patient’s cancer. RESULTS: 3D-PMB obtained a median of 50 cores (standard deviation, +/- 20.61). One hundred ten patients (61.1%) were positive bilaterally, and 41 patients (22.7%) had Gleason scores increased to 7 or higher. Thirty-six patients had negative results on 3D-PMB. Complications of 3D-PMB were self-limited and included 14 patients (7.7%) who required short-term indwelling catheter drainage and two patients with hematuria, one of whom required overnight bladder irrigation. CONCLUSION: 3D-PMB is a transperineal biopsy that can be safely used to accurately stage prostate cancer patients. At the present time, when patient management is increasingly based on the extent and characteristics of prostate cancer, 3D-PMB could have a profound effect on patient management.

J Clin Oncol. 2009 Sep 10;27(26):4321-6

Focal therapy for localized prostate cancer: a critical appraisal of rationale and modalities.

PURPOSE: Based on contemporary epidemiological and pathological characteristics of prostate cancer we explain the rationale for and concerns about focal therapy for low risk prostate cancer, review potential methods of delivery and propose study design parameters. MATERIALS AND METHODS: Articles regarding the epidemiology, diagnosis, imaging, treatment and pathology of localized prostate cancer were reviewed with a particular emphasis on technologies applicable for focal therapy, defined as targeted ablation of a limited area of the prostate expected to contain the dominant or only focus of cancer. A consensus summary was constructed by a multidisciplinary international task force of prostate cancer experts, forming the basis of the current review. RESULTS: In regions with a high prevalence of prostate specific antigen screening the over detection and subsequent overtreatment of prostate cancer is common. The incidence of unifocal cancers in radical prostatectomy specimens is 13% to 38%. In many others there is an index lesion with secondary foci containing pathological features similar to those found incidentally at autopsy. Because biopsy strategies and imaging techniques can provide more precise tumor localization and characterization, there is growing interest in focal therapy targeting unifocal or biologically unifocal tumors. The major arguments against focal therapy are multifocality, limited accuracy of staging, the unpredictable aggressiveness of secondary foci and the lack of established technology for focal ablation. Emerging technologies with the potential for focal therapy include high intensity focused ultrasound, cryotherapy, radio frequency ablation and photodynamic therapy. CONCLUSIONS: Early detection of prostate cancer has led to concerns that while many cancers now diagnosed pose too little a threat for radical therapy, many men are reluctant to accept watchful waiting or active surveillance. Several emerging technologies seem capable of focal destruction of prostate tissue with minimal morbidity. We encourage the investigation of focal therapy in select men with low risk prostate cancer in prospective clinical trials that carefully document safety, functional outcomes and cancer control.

J Urol. 2007 Dec;178(6):2260-7