PracticeUpdate Oncology February 2019

EDITOR’S PICKS 12

MenWith Clinically Detected, Localized Prostate Cancer Benefit FromRadical

COMMENT By H. Ballentine Carter MD I n the Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4), men at an average age of 65 years and non–screen detected prostate cancer were randomized to watchful waiting or radical prostatectomy over the decade from 1989 to 1999. The authors previously reported that radi- cal prostatectomy reduced metastatic progression and death from prostate cancer when compared with watchful waiting – results that persist in the cur- rent report. Now with 80% of the men dead and follow-up through 29 years, there are new findings that are important. First, the absolute difference in risk of pros- tate cancer death between groups increased two-fold between 10 and 23 years, translating into 9 men needed to treat surgically to prevent a death from prostate cancer. The estimated gain in life-years with surgery averaged 3 years at 23 years. Second, the presence of extracapsular extension and Gleason score above 7 was associated with a substantially higher risk of death from prostate cancer. As compared with Gleason score 6 or less, the presence of Gleason score 3+4 was not associ- ated with an increased risk of prostate cancer death, whereas Gleason score 4+3 and 8 or 9 was associated with a 5- and 10-fold greater risk of prostate cancer death, respectively. Thus, the findings of this study support current urology practice and guide- line recommendations that emphasize assessment of life expectancy given the long natural history of prostate can- cer, together with careful selection of men most likely to benefit from treat- ment before assigning management. This approach is even more important in the PSA era where it is estimated that men are diagnosed 5 to 10 years earlier than in the present report.

Prostatectomy The New England Journal of Medicine

Take-home message • This study randomly assigned 695 men with localized prostate cancer to watchful waiting or radical prostatectomy between 1989 and 1999 and collected follow-up data through 2017. Men with clinically detected, localized prostate cancer and a long life expectancy benefited from radical prostatectomy (RR, 0.55; absolute difference in risk, 11.7 percentage points), with a mean of 2.9 years of life gained. • These results demonstrate that a high Gleason score and the presence of extra- capsular extension in the radical prostatectomy specimens were highly predictive of death from prostate cancer. Jeffrey Wiisanen MD

Abstract BACKGROUND Radical prostatectomy reduces mortality among men with clinically detected localized prostate cancer, but evidence from randomized trials with long-term follow-up is sparse. METHODS We randomly assigned 695 men with localized prostate cancer to watchful waiting or radical prostatectomy from Octo- ber 1989 through February 1999 and collected follow-up data through 2017. Cumulative inci- dence and relative risks with 95% confidence intervals for death from any cause, death from

prostate cancer, and metastasis were estimated in intention-to-treat and per-protocol analyses, and numbers of years of life gained were esti- mated. We evaluated the prognostic value of histopathological measures with a Cox propor- tional-hazards model. RESULTS By December 31, 2017, a total of 261 of the 347 men in the radical-prostatectomy group and 292 of the 348 men in the watchful-waiting group had died; 71 deaths in the radical-prosta- tectomy group and 110 in the watchful-waiting group were due to prostate cancer (relative risk, 0.55; 95% confidence interval [CI], 0.41 to 0.74; P<0.001; absolute difference in risk, 11.7 percent- age points; 95% CI, 5.2 to 18.2). The number needed to treat to avert one death from any cause was 8.4. At 23 years, a mean of 2.9 extra years of life were gained with radical prostatec- tomy. Among the men who underwent radical prostatectomy, extracapsular extension was associated with a risk of death from prostate cancer that was 5 times as high as that among men without extracapsular extension, and a Gleason score higher than 7 was associated with a risk that was 10 times as high as that with a score of 6 or lower (scores range from 2 to 10, with higher scores indicating more aggres- sive cancer). CONCLUSIONS Men with clinically detected, local- ized prostate cancer and a long life expectancy benefited from radical prostatectomy, with a mean of 2.9 years of life gained. A high Gleason score and the presence of extracapsular exten- sion in the radical prostatectomy specimens were highly predictive of death from prostate cancer. Radical Prostatectomy or Watchful Waiting in Prostate Cancer—29-Year Follow-Up. N Engl J Med 2018 Dec 13;[EPub Ahead of Print], A Bill- Axelson, L Holmberg, H Garmo, et al. www.practiceupdate.com/c/77435

Dr. Carter is Professor of Urology, Oncology at Johns Hopkins Medicine, and Director of the Division of Adult Urology, Brady Urological Institute in Baltimore, Maryland.

PRACTICEUPDATE ONCOLOGY