Screening for prostate cancer decreases the risk of developing metastatic disease: findings from the European Randomized Study of Screening for Prostate Cancer (ERSPC)

Abstract

Background: Metastatic disease is a major morbidity of prostate cancer (PCa). Its prevention is an important goal.

Objective: To assess the effect of screening for PCa on the incidence of metastatic disease in a randomized trial.

Design, setting, and participants: Data were available for 76,813 men aged 55-69 yr coming from four centers of the European Randomized Study of Screening for Prostate Cancer (ERSPC). The presence of metastatic disease was evaluated by imaging or by prostate-specific antigen (PSA) values >100 ng/ml at diagnosis and during follow-up.

Intervention: Regular screening based on serum PSA measurements was offered to 36270 men randomized to the screening arm, while no screening was provided to the 40543 men in the control arm.

Outcome measurements and statistical analysis: The Nelson-Aalen technique and Poisson regression were used to calculate cumulative incidence and rate ratios of M+ disease.

Results and limitations: After a median follow-up of 12 yr, 666 men with M+ PCa were detected, 256 in the screening arm and 410 in the control arm, resulting in cumulative incidence of 0.67% and 0.86% per 1000 men, respectively (p<0.001). This finding translated into a relative reduction of 30% (hazard ratio [HR]: 0.70; 95% confidence interval [CI], 0.60-0.82; p=0.001) in the intention-to-screen analysis and a 42% (p=0.0001) reduction for men who were actually screened. An absolute risk reduction of metastatic disease of 3.1 per 1000 men randomized (0.31%) was found. A large discrepancy was seen when comparing the rates of M+ detected at diagnosis and all M+ cases that emerged during the total follow-up period, a 50% reduction (HR: 0.50; 95% CI, 0.41-0.62) versus the 30% reduction. The main limitation is incomplete explanation of the lack of an effect of screening during follow-up.

Conclusions: PSA screening significantly reduces the risk of developing metastatic PCa. However, despite earlier diagnosis with screening, certain men still progress and develop metastases. The ERSPC trial is registered under number ISRCTN49127736.