Radiation therapy effective for some patients with recurrent cancer after radical prostatectomy

03/11/04

For men with prostate cancer who have had their prostate removed and later show signs of cancer recurrence, several factors can help predict response to subsequent radiation therapy, according to a study in the March 17 issue of The Journal of the American Medical Association (JAMA).

Approximately 30,000 men annually in the United States will have recurrence of prostate cancer after radical prostatectomy (removal of the prostate), according to background information in the article. Salvage radiotherapy (radiation therapy following prostatectomy) may potentially cure patients whose disease recurs after radical prostatectomy, but previously gathered evidence suggests that it is ineffective in the patients at highest risk of spread of disease.

Principal investigator Kevin M. Slawin, M.D., of Baylor College of Medicine and The Methodist Hospital, Houston, and colleagues conducted a multicenter analysis of the outcome of salvage radiotherapy in a group of patients with recurrence of prostate cancer 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 (PSA) levels after radical prostatectomy. PSA is a protein that is found in the blood and that is used to detect and monitor prostate cancer.

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. "In this cohort, a Gleason score [tumor grade] of 8 to 10, preradiotherapy PSA level greater than 2.0 ng/mL, negative surgical margins [no evidence of cancer cells in the edges of the removed tissue], PSA doubling time (PSADT) of 10 months or less, and seminal vesicle invasion [cancer spreading to structures near the urinary bladder of males] were significant predictors of disease progression despite salvage radiotherapy. Yet we demonstrated that subsets of patients with high-grade disease and/or a rapid PSADT 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," the authors write.

"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 PSADT. 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 researchers write. "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 PSADT and high-grade cancer."

(JAMA. 2004;291:1325-1332. Available post-embargo at JAMA.com) Editor's Note: For information on the funding of this study and the financial disclosures of the authors, please see the JAMA article.

EDITORIAL: SALVAGE RADIOTHERAPY FOR RECURRENT PROSTATE CANCER - THE EARLIER THE BETTER

In an accompanying editorial, Mitchell S. Anscher, M.D., of Duke University Medical Center, Durham, N.C., suggests 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," Dr. Anscher writes.

"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, i.e., 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," Dr. Anscher concludes.

(JAMA. 2004;291:1380-1381. Available post-embargo at JAMA.com)

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