Several factors have been identified that help predict response to radiation therapy among patients with prostate cancer whose disease recurs after radical prostatectomy, according to an article in the March 17th issue of the Journal of the American Medical Association.

Approximately 30,000 men annually in the United States have recurrence of prostate cancer after radical prostatectomy, according to information in the article. Salvage radiotherapy may potentially cure patients with recurrent disease, but previously gathered evidence suggests that it is ineffective in the patients at highest risk for spread of disease.

Kevin M. Slawin, MD, and his American colleagues conducted a multicenter analysis of the outcome of salvage radiotherapy in a group of patients with recurrent disease after radical prostatectomy to identify variables that are associated with an effective response.

The study included 501 patients at 5 U.S. academic centers who received salvage radiotherapy between June 1987 and November 2002 for detectable and increasing prostate-specific antigen levels after radical prostatectomy.

The researchers found that over an average follow-up of 45 months, 250 patients (50 percent) experienced disease progression after treatment, 49 (10 percent) developed distant metastases, 20 (4 percent) died from prostate cancer, and 21 (4 percent) died from other or unknown causes. The 4-year progression-free probability (PFP) was 45 percent.

The authors wrote, "In this cohort, a Gleason score of 8 to 10, preradiotherapy prostate-specific antigen (PSA) level greater than 2.0 ng/mL, negative surgical margins, PSA-level doubling time of 10 months or less, and seminal vesicle invasion were significant predictors of disease progression despite salvage radiotherapy. Yet we demonstrated that subsets of patients with high-grade disease and/or a rapid PSA-level doubling time who were thought to be incurable could still achieve a durable response to salvage radiotherapy when the treatment was administered early in the course of recurrent disease. These results suggest that salvage radiotherapy may prevent metastatic disease progression for those patients at the highest risk."

"On the basis of our results, we believe that patients with positive surgical margins who experience relapse after radical prostatectomy should be strongly considered for salvage radiotherapy, even those with high-grade disease and/or a rapid PSA-level doubling time. We have developed a predictive model to estimate the likelihood of treatment success for a given individual that will help guide physicians in the selection of patients for this therapy. The clinical implications of our findings are that locally recurrent prostate cancer appears to be more common than previously reported, that it is frequently associated with aggressive features, and that salvage radiotherapy offers the possibility of cure for a substantial proportion of patients with a rapid PSA-level doubling time and high-grade cancer."

In an accompanying editorial, Mitchell S. Anscher, MD, suggested that the most important finding from this study probably could have been anticipated---Early treatment is better.

"That early treatment is better than late treatment should come as no surprise, as this is a fundamental principal of oncology. In the pre-PSA era, factors were identified that predicted for a high risk of local recurrence after radical prostatectomy, most notably positive surgical margins and the absence of seminal vesicle invasion, and these also are among the strongest predictors of success of salvage radiotherapy in the present study," Anscher wrote.

"Salvage radiation therapy after radical prostatectomy is a treatment that is used too infrequently and too late in the course of the disease. This is particularly true for patients who might benefit the most, namely, those with positive surgical margins and aggressive features who would go on to develop distant metastases if left untreated. Outside the context of a clinical trial, these patients should be offered early salvage therapy, that is, as soon as an increase in the PSA levels is confirmed. Better still, these patients are candidates for adjuvant radiotherapy, which is more effective and less toxic than salvage treatment," Anscher concluded.