By: Dan Sperling, MD
A 2011 study from a Memorial Sloan-Kettering (NY) team drew enough attention to make the news services. The authors found “found no evidence to support the recommendation that men with high PSA velocity should be biopsied in the absence of other indications; this measure should not be included in practice guidelines.”[i] Journalist Jennifer Goodwin of the HealthDay Reporter wrote that the study “… found that PSA velocity doesn’t add any useful information beyond what physicians can already tell from other methods of prostate cancer screening, including the one-time PSA level test and digital rectal exams.”[ii]
PSA is the common abbreviation for prostate specific antigen, a surface protein on prostate cells—including prostate cancer cells—that is shed into the blood stream. A blood draw is necessary to measure the amount of PSA in the blood, reported as ng/mL (nanograms per milliliter). No one really knows what a “normal” baseline PSA would be, and the standards have changed and continue to do so. If there is no objective standard for normal baseline, then the idea of an “elevated” (higher) PSA is equally confusing, because a variety of factors can stimulate the prostate cells into shedding more PSA into the bloodstream: irritation, inflammation, infection, physical stimulation such as riding a bike or having sex, a benign (noncancerous) enlargement of the gland that tends to occur with aging, and prostate cancer are the most common. Yet many men with an “elevated” PSA are sent for an invasive test called a needle biopsy, despite the fact that the PSA is not specific for prostate cancer. In fact, the American Urological Association and other professional organizations recommend that doctors discuss with patients the merits of screening for prostate cancer using the PSA test unless there are risk factors for the disease.
Tracking the rate (velocity) of a rising PSA by repeating the blood test at intervals was developed as a way to improve performance in predicting the presence of prostate cancer. To test whether this works, the Memorial Sloan-Kettering researchers combed through the detailed clinical records of 5519 men who had prostate biopsies as part of a different study. The authors factored in age, PSA, DRE, family history, and prior biopsy, with and without PSA velocity (PSAV). Specifically, they looked at the implications of using PSA velocity as triggers for biopsy in men with low PSA and negative DRE, and whether additional cancers were found or the biopsies proved unnecessary. They concluded that there were no strong associations between PSAV and prostate cancer, including aggressive prostate cancer. They recommended against PSAV screening, as it adds no useful information to PSA screening.
A very recent study out of the Department of Urology, Harvard Medical School, arrived at the same conclusion (through a review of published literature.)[iii] Noting the ongoing controversy over the use of PSA and PSAV in the screening and management of prostate cancer, they surveyed peer-reviewed articles on the subject from 1992-2013. They found considerable differences in published guidelines regarding PSA values and the interval of time over which PSA values are tracked. They concluded, “PSAV calculation has been advocated by many investigators as a strategy to improve the screening and clinical management of patients with CaP. However, when PSAV definitions are rigorously applied, its calculation does not significantly enhance the clinical performance of PSA alone.”
When wide use of PSA screening began in the early 1990s, the death rate from prostate cancer dropped significantly thanks to earlier detection of the disease. However, for almost two decades the most common treatment choices were directed at the entire gland (surgical removal or radiation). Therefore, countless men were over-treated, leaving them with impaired urinary, sexual and bowel functions. While higher PSA values have tended to correlate with the presence of prostate cancer, it reveals nothing about the localization, extent or aggressiveness of the tumors. PSA blood testing continues to prevail as a signal of prostate bioactivity, but its merit has been called into question with increasing forcefulness. Researchers, recognizing the value of advanced imaging—particularly multiparametric MRI—to provide pictorial information before recommending biopsy are increasingly advocating a larger role for scans. Even as new blood or urine tests eclipse PSA and PSAV, mpMRI will be an essential component of prostate cancer workups.
[ii] Goodwin, Jennifer. Rapid rise in PSA levels a poor predictor of prostate cancer. HealthDay Reporter, Feb. 24, 2011.
[iii] Loughlin KR. PSA velocity: A systematic review of clinical applications. Urol Oncol. 2014 June 25. Doi:10.1016/j.urolonc.2014.04.010. [Epub ahead of print] (Department of Urology, Harvard Med Sch)