Men who have a higher rate of increase in their PSA value in the year prior to their prostate cancer diagnosis have a significantly higher risk of death following radiation therapy, according to a study in the July 27 issue of JAMA.

Information obtained from serial PSA values in the form of a PSA velocity (i.e., the change in PSA level during the year prior to diagnosis) has been shown to be significantly associated with tumor stage, grade, time to prostate cancer-specific death following radical prostatectomy, according to background information in the article.

Anthony V. D'Amico, M.D., Ph.D., of Brigham and Women's Hospital and the Dana Farber Cancer Institute, Boston, and colleagues evaluated whether a PSA velocity greater than 2.0 ng/mL during the year prior to diagnosis was significantly associated with prostate cancer-specific death following radiation therapy (RT). The study, conducted between January 1989 and December 2002, included 358 men treated with RT for localized prostate cancer. One-hundred twenty-five men were classified as having low-risk prostate cancer (clinical tumor category T1c or T2a and PSA level less than 10.0 ng/mL and Gleason score 6 or less; 233 men had higher-risk disease, stratified by the PSA velocity.

The researchers found that a PSA velocity greater than 2.0 ng/mL per year was significantly associated (12 times increased risk) with a shorter time to prostate cancer-specific death and all-cause death (2.1 times the risk) when compared with men whose PSA velocity was 2.0 ng/mL per year or less. Men presenting with low-risk disease and a PSA velocity greater than 2.0 ng/mL per year had a 7-year estimate of prostate cancer-specific death rate of 19 percent compared with 0 percent for men whose PSA velocity was 2.0 ng/mL per year or less. The corresponding values for men with higher-risk disease were 24 percent and 4 percent, respectively.

"Such men [higher PSA velocity] who are planning to undergo RT and are in good health could be considered for RT combined with androgen suppression therapy because this approach improves survival in men with higher-risk disease," the authors conclude.

(JAMA. 2005;294:440-447. Available pre-embargo to the media at www.jamamedia).

Editorial: PSA Kinetics and Risk of Death From Prostate Cancer

In an accompanying editorial, Mitchell S. Anscher, M.D., of Duke University Medical Center, Durham, N.C., comments on the studies in this issue of JAMA on prostate cancer.

"As with most good retrospective studies, these 2 reports raise more questions than they answer. Given recent randomized trials reporting significant improvement in survival with chemotherapy for patients with hormone-refractory prostate cancer, a number of important questions persist: Is the definition of prostate cancer-specific mortality used in these studies still appropriate? In addition, which is the best index of change-in-PSA-with-time to use? Does it depend on the clinical situation; i.e., is PSA velocity more appropriate for newly diagnosed patients and PSADT more appropriate for patients recurring after primary therapy? What about patients who present with an abnormal result on their first-ever screening PSA measurement? Should the clinician wait 6 months and repeat the PSA measurement to calculate the PSA velocity? Also, should this information be used clinically at the present time, or are other nomograms [a chart or graphic representation of numerical relations that are connected by a line] better able to predict treatment outcome?"

"Good retrospective analyses serve to generate hypotheses for future clinical trials. The hypothesis that the rate of change in PSA with time predicts prostate cancer-specific mortality must be validated prospectively. If proven to be correct, progress in prostate cancer research will proceed at a much faster pace, since conclusive answers to clinical questions will be available in 5 to 10 years, rather than once per generation," Dr. Anscher concludes.

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