Radical prostatectomy may offer advantages over watchful waiting

Men with prostate cancer may survive longer with radical prostatectomy than watchful waiting, especially if they are younger than 65 years of age at diagnosis, a study suggested.

Between 1989 and 1999, researchers in the Scandinavian Prostate Cancer Group Study Number 4 randomly assigned 695 men with early prostate cancer to watchful waiting or radical prostatectomy. The men, treated at 14 centers in Sweden, Finland, and Iceland, were followed through 2012 for death from any cause, death from prostate cancer, the risk of metastases, and initiation of androgen-deprivation therapy. Results appeared in the March 6 New England Journal of Medicine.

The cumulative incidence of death after 18 years of the study was 56.1% in the radical-prostatectomy group and 68.9% in the watchful-waiting group, a difference of 12.7 percentage points (95% CI, 5.1 to 20.3 percentage points). This corresponded to a relative risk of death in the radical-prostatectomy group of 0.71 (95% CI, 0.59 to 0.86; P<0.001).

During 23.2 years of follow-up, 200 of 347 men in the surgery group and 247 of the 348 men in the watchful-waiting group died, an absolute difference of 11 percentage points (95% CI, 4.5 to 17.5 percentage point). Of the deaths, 63 in the surgery group and 99 in the watchful-waiting group were due to prostate cancer (relative risk, 0.56; 95% CI, 0.41 to 0.77; P=0.001).

The cumulative incidence of distant metastases at 18 years of follow-up was 26.1% in the radical-prostatectomy group and 38.3% in the watchful-waiting group, a difference of 12.2 percentage points (95% CI, 5.1 to 19.3 percentage points). Relative risk of distant metastases in the radical-prostatectomy group was 0.57 (95% CI, 0.44 to 0.75; P<0.001).

The cumulative incidence of the use of androgen-deprivation therapy at 18 years was 42.5% in the radical-prostatectomy group and 67.4% in the watchful-waiting group, a difference of 25.0 percentage points (95% CI, 17.7 to 32.3 percentage points). Relative risk of the use of androgen-deprivation therapy in the radical-prostatectomy group was 0.49 (95% CI, 0.39 to 0.60; P<0.001).

Among men who were younger than 65 years of age at diagnosis, there was a reduction of 25.5 percentage points in overall mortality, 15.8 percentage points in death from prostate cancer, and 15.8 percentage points in the risk of metastases with surgery compared to waiting. There was no significant reduction in mortality with surgery among men 65 years of age or older at diagnosis. There was a significant absolute reduction of 8.9 percentage points in the risk of metastases.

The large proportion of long-term survivors in the watchful-waiting group who never required palliative treatment provides support for active surveillance as an alternative in adequately selected groups, the researchers noted. “However, the overall long-term disease burden is also a reminder that factors other than survival should be considered when counseling men with localized prostate cancer; the risk of metastases and ensuing palliative treatments also affect quality of life,” they wrote.