Measuring the Importance of PSA Velocity
Authors: R. S. Tuma
Journal: JNCI Journal of the National Cancer Institute (2011)

A lthough controversial, the prostate-specific antigen (PSA) test is still widely used to determine whether a man should undergo a biopsy for prostate cancer. In recent years, PSA velocity, or how quickly the PSA level increases, is also being used to decide when to biopsy men for prostate cancer. Even though both the American Urological Associ ation and the National Comprehensive Cancer Network (NCCN) have made PSA velocity part of their clinical guidelines, clinicians remain divided on its relevancy, and a recent study brings that debate to the fore. In this issue of the Journal, Andrew Vickers, Ph.D. , an associate attending research methodologist at Memorial Sloan – Kettering Cancer Center in New York, and colleagues use data from the large, randomized Prostate Cancer Prevention Trial (PCPT) to test PSA velocity’s diagnostic accuracy. The team concludes that using PSA velocity, as the NCCN guidelines state, would lead to many unnecessary biopsies and should therefore be removed from the guidelines. But some experts argue that this study is just one piece in a much larger body of literature that still favors PSA velocity. The one thing both sides agree on is that not only scientific data but also personal opinion influences what makes it into clinical practice guidelines, putting the onus on physicians to use their own judgment on a case-by-case basis. Challenge Current Guidelines Clinical practice guidelines have become more common since the 1990s as the medical community has put more emphasis on management algorithms. Yet exactly what constitutes adequate evidence to support including a given approach or technique is a matter of discussion. The current NCCN guidelines state that physicians should use PSA velocity as part of early prostate cancer detection methods, specifi cally men who have a PSA below 4 ng/mL but whose PSA is rising more than 0.35 ng/mL per year should undergo a biopsy, even without other indications. In support of this approach, the guidelines cite a 2006 article in the Journal by H. Ballentine Carter, M.D. , professor of urology and oncology at Johns Hopkins Medicine in Baltimore, and colleagues ( see J. Natl. Cancer Inst. 2006;98:1521 – 7). In that study, investigators showed that in a cohort of 980 men, individuals with a PSA velocity higher than 0.35 ng/mL per year, measured 10 – 15 years before prostate cancer diagnosis, had a 4.7-fold – increased relative risk of cancerspecifi c death compared with men whose PSA velocity was 0.35 ng/mL per year or lower. According to Vickers, the 2006 study does not support the NCCN guideline. “What Carter’s data say is that PSA velocity predicts advanced cancer 10 – 15 years later,” Vickers said. “That does not address the question of whether you should biopsy a man now.” To address that question, Vickers and colleagues decided to test the NCCN guidelines by applying them to data from the PCPT — a randomized, placebo-controlled trial to test fi nasteride’s (Proscar’s) ability to prevent prostate cancer. All men in the trial had done multiple PSA tests and had undergone a biopsy at the end of the study, regardless of their PSA score. Using these data, Vickers and his colleagues calculated PSA velocity and estimated its sensitivity and specifi city for prostate cancer detection. Of the 5,519 men in the placebo arm, PSA velocity usage would have led to 548 (almost 10% of the study population) additional biopsies, 433 (79%) of which would have been negative. Moreover, had the team added PSA velocity to existing clinical factors, including digital rectal exam, age, family history, prior biopsy, and PSA to predict prostate cancer, the predictive accuracy of the model would have increased only slightly (the area under the curve increased by just 0.007). From these fi ndings, Vickers concluded that the guidelines should be changed and all references to PSA velocity should be removed. “We are evaluating exactly what the guidelines say, and when we do that we end up with a very large number of unnecessary biopsies,” he said. “There are real implications of these guidelines — people getting biopsies and a lot of anxiety.”