Time Dependence of Outcomes in the SPCG-4 Randomized Trial Comparing Radical Prostatectomy and Watchful Waiting in...

We synthesized life-long trends for outcome measures following radical prostatectomy or watchful waiting in the SPCG-4 trial, which randomized 695 patients with early prostate cancer to radical prostatectomy (RP) or watchful waiting (WW) from 1989 to 1999. We estimated trends in the relative risk of prostate cancer death, absolute risk reduction (ARR), number needed to treat (NNT), life-years gained, and changes in comorbidity following RP versus WW in the intention-to-treat population. During follow-up after randomization, cumulative prostate cancer mortality increased from 2.9% at 5 yr to 25.9% at 30 yr in the RP arm, and from 4.6% at 5 yr to 42.9% at 30 yr in the WW arm, with a corresponding increase in ARR from 1.7% to 17.0%. NNT to avert one prostate cancer death decreased from 58 to 6. Life-years were gained when follow-up was conditioned on being alive up to 20 yr after randomization. At 10-15 yr of follow-up, the WW arm had higher comorbidity than the RP arm. Treatment choices for early prostate cancer have lifelong consequences. Trial outcomes in a disease with long natural history are highly time-dependent.