Radical Prostatectomy Continues to Cut Mortality After 15 Years

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Relevance to Today's Patients Questioned

"The survival benefit with prostatectomy in men with low-risk disease is the most important new finding of the SPCG-4," said Dr. Matthew R. Smith. However, the findings may not be relevant for men today who have early-stage low-risk prostate cancers identified by prostate-specific antigen screening.

Recruited in 1989-1999, the study subjects were not identified by screening tests but by symptoms or palpable tumors. In contrast, among present-day men in the United States with newly diagnosed prostate cancer, less than half have palpable tumors, and the great majority is identified by screening tests, he noted.

Dr. Matthew R. Smith is director of the genitourinary malignancies program at Massachusetts General Hospital Cancer Center, Boston. He reported no relevant financial disclosures. These remarks were taken from his editorial accompanying Dr. Bill-Axelson’s report (N. Engl. J. Med. 2011;364:1770-2).



Among men who undergo radical prostatectomy for early prostate cancer, "there continues to be a significant reduction in the rate of death from any cause, the rate of death from prostate cancer, and the risk of metastases" 15 years after surgery, compared with "watchful waiting," according to a report in the May 5 issue of the New England Journal of Medicine.

The benefit of radical prostatectomy is even seen in men with low-risk tumors. "Our findings show that some tumors that are considered to be low risk at diagnosis do pose a threat to life, especially if they are not surgically removed," said Dr. Anna Bill-Axelson of University Hospital, Uppsala, Sweden, and her associates.

The researchers previously reported their findings from the Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4) after 9 years of follow-up, and now report estimated results at the 15-year mark in a population followed for a median of 12.8 years.

The study subjects were 695 men in Sweden, Finland, and Iceland who had newly diagnosed localized prostate cancer in 1989-1999, and were randomly assigned to either radical prostatectomy (347 patients) or watchful waiting (348 patients). The tumors were moderately well differentiated to well differentiated, and bone scan results were negative at baseline.

The subjects’ mean age at baseline was 65 years, and their mean prostate-specific antigen level was approximately 13 ng/mL.

At long-term follow-up, 55 men in the prostatectomy group and 81 in the watchful waiting group had died of prostate cancer. The cumulative incidence of death at 15 years was significantly lower – 15% – with surgery than with watchful waiting (21%). This corresponds to a relative risk of death in the radical prostatectomy group of 0.62.

Similarly, the cumulative incidence of distant metastases was significantly lower, at 22%, in the radical prostatectomy group, compared with 33% in the watchful waiting group. And the cumulative incidence of local progression was significantly lower, at 22%, with surgery, compared with 49% in the watchful waiting group.

The benefit with radical prostatectomy persisted across several subgroups. It was consistent regardless of Gleason score and prostate-specific antigen level at diagnosis. Surprisingly, even men with low-risk tumors showed rates of death due to prostate cancer and of metastases that were similar to rates in the entire study cohort, she said.

These findings "contradict the notion that there is only a distinct subpopulation that responds to radical surgery with an early reduction in risk," Dr. Bill-Axelson and her colleagues said (N. Engl. J. Med. 2011;364:1708-17).

The mortality and disease progression benefits were "obvious" among men younger than 65 years of age, "but it is still unclear whether the benefit extends to older men." In the overall cohort, the number needed to treat with radical surgery to avert one death was 15, but it was only 7 among men younger than 65.

In this study, "the apparent lack of effect in men older than 65 years of age should be interpreted with caution because, owing to a lack of power, the subgroup analyses may falsely dismiss differences," the investigators noted.

One other subgroup of patients – those found to have extracapsular tumor growth on histopathologic analysis – had poor outcomes regardless of treatment assignment. "The risk of death from prostate cancer after radical prostatectomy among men who had tumors with extracapsular growth, as compared with men who had tumors without extracapsular growth, was increased by a factor of 7," they said.

"Although extracapsular growth is not a perfect predictor of lethal disease, our findings indicate that these men could be a group for which adjuvant local or systemic therapy would be beneficial," the investigators added.

"With continued follow-up, data from the SPCG-4 study may allow us to identify prognostic markers in men assigned to watchful waiting that can serve as trigger points for active treatment." Dr. Bill-Axelson and her associates wrote.

This study was supported by the Swedish Cancer Society and the National Institutes of Health. One coauthor reported ties to Pfizer and Astellas.

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