Holmberg Trial

**A Randomized Trial Comparing Radical Prostatectomy with Watchful Waiting in Early Prostate Cancer**
Lars Holmberg, M.D., et al.
	Radical prostatectomy is widely used in the treatment of early prostate cancer. The possible survival benefit of this treatment, however, is unclear. We conducted a randomized trial to address this question. From October 1989 through February 1999, 695 men with newly diagnosed prostate cancer in International Union against Cancer clinical stage T1b, T1c, or T2 were randomly assigned to watchful waiting or radical prostatectomy. Results During a median of 6.2 years of follow-up, 62 men in the watchful-waiting group and 53 in the radical-prostatectomy group died (P=0.31). Death due to prostate cancer occurred in 31 of 348 of those assigned to watchful waiting (8.9 percent) and in 16 of 347 of those assigned to radical prostatectomy (4.6 percent) (relative hazard, 0.50; 95 percent confidence interval, 0.27 to 0.91; P=0.02)

Death due to other causes occurred in 31 of 348 men in the watchful-waiting group (8.9 percent) and in 37 of 347 men in the radical-prostatectomy group (10.6 percent). The men assigned to surgery had a lower relative risk of distant metastases than the men assigned to watchful waiting (relative hazard, 0.63; 95 percent confidence interval, 0.41 to 0.96).

Conclusions In this randomized trial, radical prostatectomy significantly reduced disease-specific mortality, but there was no significant difference between surgery and watchful waiting in terms of overall survival. N Eng J Med 2002:347:781

in 2005 they publ;ished a longer term follow u[p that showed overall survival (not just from prostate cancer) was better in treated patients... see below

NEJM 2005;352:1977 In 2002, we reported the initial results of a trial comparing radical prostatectomy with watchful waiting in the management of early prostate cancer. After three more years of follow-up, we report estimated 10-year results.

From October 1989 through February 1999, 695 men with early prostate cancer (mean age, 64.7 years) were randomly assigned to radical prostatectomy (347 men) or watchful waiting (348 men). The follow-up was complete through 2003, with blinded evaluation of the causes of death. The primary end point was death due to prostate cancer; the secondary end points were death from any cause, metastasis, and local progression.

Results During a median of 8.2 years of follow-up, 83 men in the surgery group and 106 men in the watchful-waiting group died (P=0.04). In 30 of the 347 men assigned to surgery (8.6 percent) and 50 of the 348 men assigned to watchful waiting (14.4 percent), death was due to prostate cancer. The difference in the cumulative incidence of death due to prostate cancer increased from 2.0 percentage points after 5 years to 5.3 percentage points after 10 years, for a relative risk of 0.56 (95 percent confidence interval, 0.36 to 0.88; P=0.01 by Gray's test). For distant metastasis, the corresponding increase was from 1.7 to 10.2 percentage points, for a relative risk in the surgery group of 0.60 (95 percent confidence interval, 0.42 to 0.86; P=0.004 by Gray's test), and for local progression, the increase was from 19.1 to 25.1 percentage points, for a relative risk of 0.33 (95 percent confidence interval, 0.25 to 0.44; P<0.001 by Gray's test).
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Conclusions Radical prostatectomy reduces disease-specific mortality, overall mortality, and the risks of metastasis and local progression. The absolute reduction in the risk of death after 10 years is small, but the reductions in the risks of metastasis and local tumor progression are substantial. Our 10-year estimates show that radical prostatectomy is associated with a statistically significant reduction in all the end points that we investigated, with a relative reduction of 44 percent in mortality due to prostate cancer, of 26 percent in overall mortality, of 40 percent in the risk of distant metastasis, and of 67 percent in local progression. Since, in absolute terms, the reduction in mortality is moderate, clinical decision making and patient counseling will remain difficult. The additional finding that radical prostatectomy substantially reduces the risk of metastasis and symptomatic local tumor growth may, however, be of some help in guiding therapy, and we expect that the benefits of this surgery will increase during longer periods of follow-up.