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European UrologyVolume 60, issue 4, pages e29-e36, October 2011
Words of Wisdom
Re: Radical Prostatectomy Versus Watchful Waiting in Early Prostate Cancer
Published online 27 August 2011, pages 868 - 869
Bill-Axelson A, Holmberg L, Ruutu M, et al
N Engl J Med 2011;364:1708–17
This article presents long-term (median: 12.8 yr) follow-up of the Scandinavian Prostate Cancer Group 4 (SPCG-4) trial, which randomized 695 men aged <75 with prostate-specific antigen (PSA) ≤50 ng/ml and ≤T2N0M0 well- or moderately differentiated prostate cancer between 1989 and 1999. Progression in both arms was managed with androgen deprivation. When tumors were regraded in 1999, >60% were Gleason ≤6 and only 5% were Gleason ≥8. Mean age at diagnosis was 65, mean PSA was 12.9 ng/ml, and most tumors were clinically detected.
By the end of 2009, 367 (53%) of the 695 men had died, 136 (37%) from prostate cancer. The absolute and relative risk reductions for cancer-specific mortality for prostatectomy relative to watchful waiting were 6.1% and 38%, respectively. For all-cause mortality, these reductions were 6.6% and 25%, respectively, again, in favor of surgery. Subgroup analysis found that these differences were observed even among men with low-risk disease (Gleason score <7 and PSA <10 ng/ml) but that there was no difference in outcomes between groups for men aged >65.
The results of this well-executed trial yield important insights into the evolving role of local treatment for prostate cancer. However, care should be taken in applying these findings to men diagnosed in contemporary practice. Tumors in the SPCG-4 cohort were generally clinically detected, and the lead time to clinical significance for contemporary screen-detected tumors may be even longer. Conversely, however, the cohort included few men with high-grade tumors, who may in fact be those who benefit most from surgery  and .
The findings of the subgroup analyses—that the benefits of surgery over watchful waiting persist across risk groups but not across age strata—are somewhat counterintuitive. In contrast, the Prostate Cancer Intervention Versus Observation Trial (PIVOT), recently reported at the American Urological Association annual meeting, randomized men between surgery and observation between 1994 and 2002. This cohort had mostly screen-detected tumors, and a survival benefit was found at 10 yr only for those with higher-risk tumors.
An analysis of older men treated conservatively for localized prostate cancer found that for those with high-grade tumors, likelihood of cancer-specific mortality approached 25% at 10 yr, even for those aged >80 at diagnosis , yet treatment decisions in the United States tend to reflect age more than disease risk, leading to high rates of both overtreatment of low-risk disease and undertreatment of high-risk disease among older men . Other recent studies have likewise highlighted the greater role that comorbidity, rather than age alone, should play in driving both screening and management decisions  and . Ultimately, the SPCG-4 trial provides important evidence in favor of intervention for localized prostate cancer, but further work is needed to identify which men will ultimately benefit most from treatment.
Conflicts of interest
The author has nothing to disclose.
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University of California, San Francisco, Urology, 3025 Scott St., San Francisco, CA 94123, USA
© 2011 Published by Elsevier B.V.
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