Prostate Diagnostic and Assessment TestsDecember 2013
By Michael Downey
There are now a number of diagnostic tests to identify early stage prostate cancer and then monitor the success or failure of a wide range of treatment options.
This article succinctly describes conventional prostate gland diagnostic tests along with those that mainstream medicine often overlooks, to the detriment of their patients. All of these tests, however, are commercially available.
1. PSA (Prostate-Specific Antigen)
Perhaps the greatest breakthrough in the detection and management of prostate cancer was the approval of the prostate-specific antigen (PSA) blood test in 1986, but it was only approved for men already diagnosed with prostate cancer.1 It wasn’t until 1994 that the FDA approved the PSA test as a prostate cancer screening test for all men.1 Prostate-specific antigen is a protein produced by the cells of the prostate gland, including both cancerous cells as well as cells that are benign.1 Since very little PSA escapes into the bloodstream from a healthy prostate, an elevated PSA level in the blood indicates an abnormal condition of the prostate gland—which can be either benign or malignant. PSA test results can be used both to detect potential prostate problems and to follow the progress of prostate cancer therapy.1
Because tumor growth is essentially exponential, with one cell dividing into two, two to four, four to eight, and so on, a tumor cell product such as PSA can reflect such exponential growth—measuring the time it takes for PSA to double (PSA doubling time, or PSADT).2 Also, the PSA rate of rise (PSA velocity), although not a more specific marker, may have value in prostate cancer prognosis—because men with prostate cancer whose PSA level increased by more than 2.0 ng/mL during the year before their diagnosis showed a higher risk of death from prostate cancer.3 Additionally, though not an absolute criteria for or against malignancy, PSA velocity can serve as a gauge regarding the likelihood of a malignant condition.2 A rising PSA velocity in excess of .75 ng/mL/year relates to an increased probability of a malignant condition. 2
The reference interval provided by most conventional laboratories for the PSA test is 0.00-4.00 nanograms per milliliter (ng/mL).4 Conventional reference ranges suggest that PSA levels under 4.0 ng/mL are normal, but any reading over 2.0 ng/mL can indicate unhealthy activity, such as prostatitis, benign prostate hypertrophy, or prostate cancer.2 If PSA readings begin to elevate, there are interventions that can reduce or stabilize the production of PSA, shutting down a mechanism used by cancer cells to escape their confinement within the prostate gland.5 PSA readings can increase immediately after ejaculation, returning slowly to baseline levels within 24-48 hours.6,7
2. Free PSA
Free PSA is a newer evaluation for prostate health. Most PSA in the blood is bound to serum proteins, but a small amount is not protein-bound and is called free PSA.2,8 In men with prostate cancer, the ratio of free (unbound) PSA to total PSA is decreased.2 The free PSA test measures the percentage of free PSA relative to the total amount.9 The lower the ratio, the greater the probability of prostate cancer. Measuring free PSA may help eliminate unnecessary biopsies.8 Free PSA readings increase immediately after ejaculation, returning slowly to baseline levels within about 24 hours.6 Although not used as an initial screening test, a lower percentage of free PSA might mean your doctor needs to do a further workup.
Below are the percentage of PSA ranges and what they represent as far as prostate cancer risk. Note that when the percentage of free PSA is high (over 20%), this means the risk of prostate cancer is low, whereas a low percentage of free PSA (under 11% indicates high risk).
3. PCA3 Urine
PCA3 is a molecular diagnostic test performed on urine rather than blood and detects mRNA that is excreted into the urethra via the epithelial cells that line the prostatic ducts.10 Prostate cancer cells tend to produce this compound far more than normal cells do.10 The PCA3 urine test has to be done in a urologist’s, or other doctor’s, office, because it requires a digital rectal massage just prior to collection of the urine. 11
PCA3 testing is most useful when repeated over a period of time to monitor for changes in the observed value. In general, a PCA3 score of 35 is considered the optimal cut-off. A score of greater than 35 reflects an increased probability of a positive biopsy. A score of less than 35 reflects a decreased probability of a positive biopsy.
4. 25-Hydroxy Vitamin D
Research points to a connection between vitamin D levels and cancer.12,13 Experimental studies indicate that low levels of vitamin D increase prostate cancer risk.14 And further evidence shows that the active form of vitamin D promotes differentiation and inhibits proliferation, invasiveness, and metastasis of human prostate cancer cells.14,15 Detecting deficient levels allows you and your physician to implement vitamin D supplementation to help avert illnesses associated with inadequate vitamin D levels. For this nutrient, individualized dosing is of particular importance, and the only way to accomplish this is through vitamin D blood testing. Although conventional laboratory reference ranges list a reference interval of 30-100 ng/mL, Life Extension supports maintaining vitamin D in the 50-80 ng/mL range.16
Prolactin, a peptide hormone largely secreted by the anterior pituitary gland, has typically remained restricted to the fields of lactation and infertility. However, researchers discovered that prolactin plays a major role in the differentiation and development of the prostate gland.17 Both malignant and healthy prostates produce prolactin. Prostatic fluids from patients with cancer also have higher prolactin levels than controls. 17 In vitro, prolactin induces proliferation and antagonizes apoptosis in prostate organ culture and in some tumor cell lines.17 Increased levels of prolactin have significant stimulatory action on the prostate and on prostate ductal development and may lead to hyperplastic growth, independent of elevations in circulating androgen levels.18
Labcorp normal reference range - Male: 4.0-15.2 ng/mL
Optimal for Prostate Cancer- <5 ng/mL
6. DRE (Digital Rectal Exam)
Men can easily be tested for palpable prostate abnormalities with a digital rectal exam (DRE), a simple test that provides a lot of information.19 It gives the physician a sense of the prostate gland volume. The bigger the prostate, the more PSA the gland is entitled to make without indicating a potential problem. A basic rule is that the prostate gland volume multiplied by the amount of PSA produced per unit of volume in benign prostate tissue is 0.067 ng.19 This means that a 50-year-old man with a normal size prostate of 30 grams (or cubic centimeters) would therefore be entitled to make approximately 2 ng of PSA. If such a man has a PSA of 4.0 ng/mL, it would indicate an excess of about 2 ng of PSA and the need for further investigation to rule out prostate cancer.
In addition to estimating prostate gland volume and calculating the benign cellular contribution to the total PSA value, the DRE can also aid in finding hard nodules or other evidence of disease. Palpable (able to be felt) abnormalities of the prostate gland relate to tumor volume, also called tumor burden.19 In the years before routine testing with PSA, most prostate cancers were already palpable via DRE by the time of diagnosis. Today, close to 70% of prostate cancers newly diagnosed in the US are no longer associated with palpable disease.19 This shows the value of PSA screening in allowing an earlier diagnosis of prostate cancer — before the cancer has had a chance to get bulkier and manifest itself as a palpable disease, known as a T2 disease. Most American men when first diagnosed with prostate cancer have non-palpable, or T1, prostate cancer.19
7. Blood Hormone Profile
A comprehensive blood test for specific hormone levels is useful. In addition to the free and total testosterone levels covered earlier, a complete blood test should include levels of estradiol, DHT (dihydrotestosterone), pregnenolone, DHEA-S (dehydroepiandrosterone sulfate), FSH (follicle-stimulating hormone, LH (luteinizing hormone), and possibly, IGF-1 (insulin-like growth factor 1). DHT plays a role in the development and exacerbation of benign prostatic hyperplasia, as well as prostate cancer.20 FSH (follicle-stimulating hormone) and LH (luteinizing hormone) regulate the reproductive processes of the body, and in aging men, a rise in FSH and LH can be indicative of andropause.21,22 Studies have shown that increased levels of IGF promote cancer growth and confer resistance to conventional treatments (chemotherapy and radiation).23,24
8. PAP (Prostatic Acid Phosphatase) Test
The PAP test is a simple blood test, used to measure the amount of an enzyme—called prostatic acid phosphatase (PAP)—that is produced by prostate epithelial cells and is abundant in seminal fluid.25 Higher levels of PAP are associated with prostate cancer.25 PAP determination, in conjunction with PSA measurements, is useful in assessing the prognosis of prostate cancer. It is an important test, because it allows identification of prostate cancer patients who have an elevation of PAP, but not of PSA. This helps monitor the course of disease and response to treatment.
9. Circulating Tumor Cells Assay
This test provides a measurement of cancer cells that have separated from a solid tumor site and are circulating in the bloodstream.26 Detecting the presence of circulating tumor cells in the blood has clinical usefulness in assessing the disease status and prognosis of metastatic prostate cancer, and is predictive of overall survival.27 Fasting prior to the blood draw is not required.