SAN FRANCISCO — Among men with early-stage prostate cancer who choose watchful waiting as their primary treatment strategy, the rate of rise in prostate-specific antigen level is more predictive of survival than any single PSA value, Dr. Jennifer Cullen said at a symposium on prostate cancer sponsored by the American Society of Clinical Oncology.

In a retrospective study of nearly 1,400 men with early prostate cancer being followed with watchful waiting rather than active intervention, those men with a PSA velocity (the rate of increase in PSA value) of less than 2 ng/mL per year during a mean follow-up time of nearly 5 years had a significantly better overall survival rate than did those men whose PSA velocity was 2 ng/mL per year or greater, said Dr. Cullen of the Department of Defense Center for Prostate Disease Research (CPDR) in Rockville, Md.

The study sample consisted of military-care beneficiaries from the CPDR database who were diagnosed with biopsy-proven, clinically localized prostate cancer between January 1989 and December 2003 and who did not receive any clinical intervention for their cancer for at least 6 months following diagnosis. Of the 1,369 men who met these criteria, the survival analysis was limited to 830 men who had record of at least one follow-up appointment in the first 3 years following diagnosis, “to be sure that no other therapy was chosen at some time point after their care in the [CPDR] database program,” Dr. Cullen said.

All participants had at least three PSA values recorded after diagnosis and were taken more than 3 months apart, to minimize the potential for noise-related inaccuracies that could occur in shorter intervals, she said. Mean patient age was 69 years, and mean follow-up time was nearly 5 years.

The investigators generated survival analyses for men with PSA velocities below 2 ng/mL and those with velocities equal to or greater than 2 ng/mL—a distinction that is literature driven, Dr. Cullen said.

After controlling for comorbidities, secondary treatment, and time to secondary treatment, “we observed significantly poorer survival for those men in the higher PSA velocity group independent of PSA value at diagnosis,” she said. “Only 56% of men in the higher-velocity category were alive at follow-up, compared with 87% of those with lower velocity values.”

On the heels of the recent report by the Scandinavian Prostate Cancer Group Study No. 4, a long-term trial showing small but statistically significant overall and disease-specific survival differences between watchful waiting and radical prostatectomy (N. Engl. J. Med. 2005;352:1977–84), the findings of this study shed light on how best to evaluate the survival potential associated with watchful waiting for a given patient, Dr. Cullen noted at the meeting, cosponsored by the Society of Urologic Oncology and the American Society for Therapeutic Radiology and Oncology. The Scandinavian study “did not specifically investigate factors that might impact survival in men who choose watchful waiting,” she said. “Our goal was to look for characteristics that might be predictive of better or worse outcomes.”

Although limited by its retrospective design, “our database is so large that we have the ability to do robust subset analyses such as this one,” Dr. Cullen said. The findings, though promising, need to be replicated in a nonmilitary population. In addition, she said, “we want to look at the relative impact of other survival predictors, including patient age, specific tumor characteristics, and Gleason scores, as well as the optimal frequency of PSA testing.”

Laura Tanturri De Horatio, MD

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