Radical Prostatectomy or Observation in Early Prostate Cancer

Results of a randomized trial [N Engl J Med. 2012;367(3):203-213] showed no significant reduction in all-cause or prostate-cancer mortality in men with clinically localized prostate cancer treated by radical prostatectomy compared with observation followed for at least 12 years. The findings were particularly strong for men with prostate-specific antigen (PSA) levels of ≤10 ng per milliliter or among men with low-risk tumors. Radical prostatectomy may reduce mortality in men with higher prostate-specific antigen (PSA) values and higher risk tumors.

For men with early prostate cancer, treatment remains controversial with insufficient evidence on which to assess the comparative effectiveness of treatments. Observation has been shown to confer excellent long-term, disease-specific survival, but randomized evidence comparing it with radical prostatectomy is lacking.

To fill this gap, the current study randomized 731 patients with early prostate cancer to radical prostatectomy (n=364) or observation (n=367). Patients were recruited from 44 U.S. Department of Veterans Affairs sites and 8 National Cancer Institute sites and enrolled in the study between 1994 and 2002, during a time of widespread PSA testing. All patients had clinically localized prostate cancer (stage T1-T2NxM0) with a PSA value of <50 mg per milliliter and a negative bone scan for metastatic disease. Additionally, patients were ≤75 years of age and had a life expectancy of at least 10 years.

The main outcome of the study was all-cause mortality, and the secondary outcome was prostate-cancer mortality defined as death that was definitely or probably due to prostate cancer or prostate-cancer treatment.

Patient characteristics of the 731 patients enrolled in the study were a mean age of 67 years, a mean PSA value of 7.8 mg per milliliter, stage T1c disease in 50%, histologic scores of 7 or higher on the Gleason scale in 25%, and low-, intermediate-, and high-risk disease in 40%, 34%, and 21%, respectively.

The study found no difference in all-cause mortality at a median follow-up of 10 years. Of the 364 patients treated with radical prostatectomy, 171 (47%) died compared to 183 of 367 (49.9%) in the observation group (hazard ratio[HR], 0.88; 95% confidence interval [CI], 0.71 to 1.08; P=.22). Median survival in the radical prostatectomy group was 13.0 years (95% CI, 12.2 to 13.7) and 12.4 years (95% CI, 11.4 to 13.1) in the observation group.

The absolute reduction in mortality with radical prostatectomy was not significant at any interval and declined over time from 4.6 percentage points (95% CI, -0.2 to 9.3) at 4 years to 2.9 percentage points (95% CI, -4.2 to 10.0) at 12 years.

The study also found no difference in prostate-cancer mortality, with death from prostate cancer or treatment occurring in 21 of 362 patients (5.8%) treated with radical prostatectomy compared with 31 of 367 patients (8.4%) in the observation group (HR, 0.63; 95% CI, 0.36-1.09; P=.09).

Compared with observation, the study found that the effect of radical prostatectomy on all-cause mortality and prostate-cancer mortality did not differ significantly according to race, age, self-reported performance status, Gleason score, or Charlson comorbidity index score.

A reduction in all-cause mortality was found among men treated by radical prostatectomy with a PSA >10 ng per milliliter (P=.04 for interaction) and possibly among those with intermediate- or high-risk tumors (P=.07 for interaction).

Overall, perioperative complications in the patients who underwent radical prostatectomy occurred in 21.4% of patients during the first 30 days of surgery and included 1 death; infection was the most common complication, occurring in 4.3% of patients. Urinary incontinence and erectile dysfunction were significantly more common at 2 years in the patients who underwent radical prostatectomy compared with the observation group.

According to the authors, these results add to the evidence that supports observation and possibly surveillance for most men diagnosed with localized prostate cancer, particularly those diagnosed with a low PSA value and low-risk disease.