Prostate cancer mortality among men with and without comorbidity: Long-term results from the European randomized study of screening for prostate cancer Rotterdam

INTRODUCTION: Prostate-specific antigen (PSA)-based prostate cancer (PCa) screening can be improved by individualised, risk-stratified strategies. Comorbidity influences life expectancy, so may affect benefits of screening. We evaluated whether the effect of PSA-screening on PCa-specific mortality (PCSM) differed between men with and without comorbidity at baseline. METHODS: In the screening arm of the European Randomized Study of Screening for PCa Rotterdam, PSA-testing was offered every four years. Comorbidity was assessed at randomisation using a self-reported questionnaire, defined as no versus ≥ 1 according to the Charlson Comorbidity Index. Cumulative incidences for metastases and PCSM, accounting for competing risks, were estimated for both comorbidity strata. Rate ratios (RRs) of screening versus control were estimated, adjusted for age at randomisation, with an interaction-term. Absolute risk reductions were calculated. Main analyses were conducted in men 55-69 years; men ≥ 70 years were analysed separately. RESULTS: At 21 years, among men with comorbidity at baseline the risks of metastases (RR:0.87; 95%CI 0.64-1.17) and PCSM (RR:1.09; 95%CI 0.76-1.56) did not differ significantly between the screening and control arm. Without comorbidity, metastases (RR:0.62; 95%CI 0.52-0.72) and PCSM (RR:0.67; 95%CI 0.54-0.83) were lower in the screening arm than in the control arm. The absolute PCSM risk reduction was 5.4 per 1000 men (95%CI 2.4-8.2). No difference in PCSM was observed among men ≥ 70 years, regardless of comorbidity at baseline. CONCLUSION: PSA-screening did not reduce metastases and PCSM in men ≥ 55 years with comorbidity. In contrast, it did in men 55-69 years without comorbidity. This supports consideration of comorbidities in screening.