Radical prostatectomy was associated with fewer deaths from prostate cancer compared to watchful waiting, a Scandinavian study found. But the results may not apply in the U.S., where more prostate-specific antigen (PSA) testing occurs.
Researchers in the Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4) randomized 695 men with early prostate cancer to watchful waiting or radical prostatectomy from October 1989 to February 1999. Follow-up occurred through December 2009. Researchers presented results in the May 5 New England Journal of Medicine. The study follows up on the group's 2008 report with an additional three years of data to present 15-year results.
Upon study enrollment, 12% of the patients had nonpalpable T1c tumors. The mean PSA level was approximately 13 ng/mL. During a median follow-up of 12.8 years, 367 of the 695 men enrolled in the study had died from all causes—166 of the 347 men in the radical-prostatectomy group and 201 of the 348 in the watchful-waiting group (P=0.007).
The cumulative incidence of death from prostate cancer at 15 years of follow-up was 14.6% in the surgical group and 20.7% in the surveillance group (relative risk with surgery, 0.62; P=0.01). The number needed to treat to avert one death was 15 overall and 7 for men younger than 65 years of age. Among men who underwent surgery, those with extracapsular tumor growth had a risk of death from prostate cancer 7 times more than men without it. Cumulative incidence of local progression at 15 years was 21.5% in the surgical group and 49.3% in the surveillance group. Cumulative incidence of distant metastases at 15 years was 21.7% in the surgical group and 33.4% in the surveillance group.
A total of 124 men in the surgical group and 139 in the surveillance group had a PSA level of less than 10 ng/mL and a tumor with a Gleason score of less than 7 or a WHO of grade 1. Among them, 42 in the surgical group and 68 in the surveillance group died. In men with low-risk disease, the absolute benefit of surgery with respect to death from prostate cancer and the risk of metastases was similar to that in the whole cohort.
But researchers noted that the study's low-risk group cannot be compared directly with other studies because few of them had a tumor found by a PSA screening test. The biopsy protocol for the SPCG-4 study also had a lower sensitivity for diagnosing high-risk disease than other studies. More follow-up may identify prognostic markers in men assigned to surveillance that can serve as trigger points for active treatment, the study authors said.
“The benefit of radical prostatectomy continued to be seen beyond 9 years, which contradicts the notion that there is only a distinct subpopulation that responds to radical surgery with an early reduction in risk,” the researchers wrote. “The finding that some low-risk tumors will progress and become lethal emphasizes the importance of protocols with well-defined end points at which men in active surveillance switch to curative treatment.”
An editorialist commented that the survival benefit of radical prostatectomy in men with low-risk disease is the most important new finding of SPCG-4, but that it may not apply to low-risk, early-stage prostate cancers identified by PSA screening. Compared to SPCG-4 patients, American men newly diagnosed with prostate cancer have far fewer palpable tumors and are far more likely to have tumors identified by PSA. Two large, randomized, controlled trials are under way to determine whether treatment will reduce mortality in men with prostate cancer identified through PSA screening.