Background: The Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4) trial showed that radical prostatectomy (RP) reduced prostate cancer deaths with an absolute mortality difference (AMD) between the RP and watchful waiting arms of 6.1% (95% confidence interval [CI] = 0.2% to 12.0%) after 15 years. In the United States, the Prostate Cancer Intervention Versus Observation Trial (PIVOT) produced an AMD of 3% (95% CI = -1.1% to 6.5%) after 12 years. It is not known whether a higher frequency of screen detection in PIVOT explains the lower AMD.
Methods: We assumed the SPCG-4 trial represents RP efficacy and prostate cancer survival in an unscreened population. Given the fraction of screen-detected prostate cancers in PIVOT, we adjusted prostate cancer survival using published estimates of overdiagnosis and lead time to project the effect of screen detection on disease-specific deaths.
Results: On the basis of published estimates, we assumed that 32% of screen-detected cancers were overdiagnosed and a mean lead time among non-overdiagnosed cancers of 7.7 years. When we adjusted prostate cancer survival for the 76% of case patients in PIVOT who were screen detected, we projected that the AMD after 12 years would be 2.0% (95% CI = -1.6% to 5.6%) based on variation in published estimates of overdiagnosis and mean lead time in the United States.
Conclusions: If RP efficacy and prostate cancer survival in the absence of screening are similar to that in the SPCG-4 trial, then overdiagnosis and lead time largely explain the lower AMD in PIVOT. If these artifacts of screening are the correct explanation, then there is a subset of case subjects that should not be treated with RP, and identifying this subset should lead to a clearer understanding of the benefit of RP in the remaining cases.