Originally published 1/7/2018
Wow, so much has happened since the original blog was posted nearly three years ago! The FDA-approved PCA3 urine test (Progensa) for detecting a biomarker that is overexpressed in prostate cancer (PCa) was acknowledged by the American Urological Association as far back as 2013 as a useful adjunct – along with other PSA derivatives – for determining if a biopsy or repeat biopsy was needed. Since the original blog below was written, the manufacturer changed the cutoff value for a positive test from 35 to 25. Perhaps the PCA3 had an even greater benefit for men, since it opened the way to developing other noninvasive, urine-based biomarker tests for PCa.
There have been some significant developments since then, especially two available urine tests that DO NOT require a digital rectal exam immediately prior to collecting a urine sample:
- SelectMDx measures the expression of two messenger RNA biomarkers that can indicate a dangerous PCa cell line; it can help determine if a biopsy is indicated. By FDA standards, no approval ruling was needed for this type of laboratory analysis.
- ExoDx Prostate Test was granted breakthrough status by the FDA in 2019. It measures three PCa-specific biomarkers that are linked with dangerous PCa, and can help with a biopsy decision as well as treatment decisions.
There is a 3rd test in development in Great Britain called the PUR test (Prostate Urine Risk) that “…measures the expression of approximately 30 genes in urine and gauges the rate at which certain functional units in the cell are being produced.”[i] It would be available as a home test kit. The researchers behind PUR believe it can identify 8 times as many men who will need aggressive whole-gland treatment within 5 years of diagnosis. However, large-scale clinical trials are needed before early clinical trial results can be validated and the test commercially distributed.
Most importantly, opinion is building that the PCA3 test alone does not discriminate aggressive PCa as well as newer tests such as those above.[ii] If you receive a suspiciously high PSA blood test result, talk to your doctor about the merits of the newest generation of urine tests, and remember that in addition to biomarkers, 3T multiparametric MRI (mpMRI) of the prostate gives key visual information that a blood or urine test alone cannot provide.
The PCA3 urine test detects prostate cancer better than the PSA blood test – true or false? If you answered true, you are on the right track. The PSA test is not a clear indication of cancer because an elevated number merely signals an unknown way in which the prostate gland is being stimulated. Yes, it could be cancer, but it could also be an infection, inflammation, or an age-related enlargement of the gland (BPH). In fact, riding a bicycle, having sex, and even having a digital rectal exam can temporarily bump up the PSA.
On the other hand, the PCA3 urine test is much more specific for prostate cancer. The urine is collected following a digital rectal exam (DRE) that causes the prostate to shed whole prostate cells into the urine. These cells can then be analyzed for a certain gene associated with the presence of cancer. Thus, the PCA3 is “a molecular biology assay that measures the expression of PCA3 (prostate cancer gene 3) mRNA [messenger RNA] in urine samples.”[iii] The analysis gives a numeric score, and the cutoff point (“red flag”) for cancer is considered to be 35 or higher. One study even suggested that for men who have never had a prostate biopsy, a score of 60 or higher suggests a high likelihood that a biopsy will find cancer.
PCA3 not entirely accurate
However, the PCA3 urine test is not 100% accurate. “There have been many reports of men with PCA3 scores of > 100 who have been found to be negative for prostate cancer after multiple biopsies,” according to one author.[iv] Nonetheless, it still has value for patients who have already had one or more biopsies that did not find cancer. For them, several published studies support that the PCA3 test can help avoid an unnecessary repeat biopsy if it returns a score under 35.
Not having to have a prostate biopsy is usually a relief. No one enjoys undergoing a transrectal ultrasound (TRUS) guided biopsy with its risks of pain, bleeding, and infection. Patients suspected of having prostate cancer, or those who have been treated but may be at risk for recurrence, all wish there were a simple “liquid biopsy” (blood or urine test) that did not involve sticking needles into the prostate gland but was accurate.
No liquid biopsy yet
If doctors and patients were hoping that the PCA3 would satisfy the requirements of an accurate prostate cancer urine-based biopsy, they will be disappointed. At this point, the PCA3 is a useful tool to help determine if a patient needs a biopsy. It even has a limited prognostic (predictive) value because it can help stratify patients according to risk level; high PCA3 scores are correlated with the presence of more aggressive prostate cancer. The problem is, it’s not reliably accurate with an unknown percentage of cases. Researcher Andrew Vickers, Ph.D. (Memorial Sloan Kettering Cancer Center, New York) is quoted by Medscape Medical News as stating that “in the initial biopsy setting, the risk that you’ll have a low PCA3 but still have an aggressive cancer is higher than most urologists would be comfortable with.”[v] This means that PCA3 is not entirely reliable for determining whether a man who has never had a biopsy can safely avoid one.
Genomic analysis is undoubtedly a game changer in detecting and diagnosing prostate cancer. It is not yet a foolproof, stand-alone diagnostic measure, but it’s an important addition to the diagnostic toolkit.
Equally valuable is 3T multiparametric MRI (3T mpMRI) imaging. When determining if a patient needs a prostate biopsy, the combination of PSA, a genomic test like PCA3, and 3T mpMRI gives the most comprehensive information. Furthermore, if a biopsy is indicated, an in-bore MRI-guided biopsy significantly reduces the risks of a TRUS biopsy by minimizing the number of needles, yet provides the highest diagnostic accuracy.
For more information about 3T mpMRI and its benefits for men suspected of prostate cancer or post-treatment recurrence, contact the Sperling Prostate Center.
[ii] Press B, Schulster M, Bjurlin MA. Differentiating Molecular Risk Assessments for Prostate Cancer. Rev Urol. 2018; 20(1): 12–18.