Background The European Randomized study of Screening for Prostate Cancer (ERSPC) is a randomized multi-center trial with a predefined centralized database, analysis plan and core age group (55–69 years) evaluating prostate-specific antigen (PSA) testing in eight European countries. Methods The present results are based on prostate cancer (PCa) incidence and mortality truncated at 9, 11, and 13 years of follow-up in the intervention arm (offered PSA testing) relative to the control arm. A secondary analysis corrected for selection bias due to non-participation was performed. Because of incomplete follow-up, only incidence and no mortality data at 9 years follow-up are reported for the French centers. Findings The rate ratio (RR) of PCa incidence between the intervention and control arms was 1.91 after 9 years (1.64 including France), 1.66 after 11 years and 1.57 after 13 years. The RR of PCa mortality was 0.85, 0.78 and 0.79 at 9, 11 and 13 years respectively (95% confidence interval 13-year 0.69–0.91, p = 0.001). This corresponds to a relative risk reduction of 21% and an absolute risk reduction of death from PCa at 13 years of 0.11 per 1,000 person-years or 1.28 per 1,000 men randomized, which is equivalent to one PCa death averted per 781 men invited for screening or one per 27 additional PCa detected. PCa mortality reduction in screened men after adjustment for non–participation was 27%. Interpretation This update of ERSPC confirms a substantial PCa mortality reduction due to PSA testing, with a substantially increased absolute effect at 13 years compared to findings after 9 and 11 years. Funding All sources of funding per center are indicated in the “Web extra material” section. Trial identification This trial is registered under Current Controlled Trials number: ISRCTN49127736.

Summary Background Several trials have evaluated the effect of prostate-specific antigen (PSA)-based screening on prostate cancer (PC) mortality, with conflicting results. We report on the mortality in the European Randomized Trial of Screening for Prostate Cancer (ERSPC) with two added years of follow-up. Methods The ERSPC is a randomized screening trial in men aged 50 – 74 years (N=182,160) at entry, with a predefined core age group of 55 – 69 years (N=162,388) conducted in eight European countries Men randomized to the intervention arm were offered prostate specific antigen (PSA)-based screening while those in the control arm were not offered screening. The primary outcome is PC mortality. Results After a median follow-up of 11 years the relative risk reduction for PC death in the intention to screen analysis was 21% (risk ratio 0.79, 95%CI 0.68 – 0.91, p=0.001), and 29% for screened men after correction for non-compliance in the core age group. The absolute difference in mortality amounted to 0.10 per 1000 person years or 1.07 per 1000 men randomized. The rate ratio of PC mortality during the follow-up years 10 -11 was 0.62 (95% CI 0.45 – 0.85, P=0.003). The numbers needed invite (NNI) and detect (NND) to prevent one PC death amounted to 1055 and 37 at 11 years of follow-up and 936 and 33 for the entire follow-up. There was no difference in all-cause mortality. Conclusions Two added years of follow-up consolidate our previous finding that PSA-based screening reduces PC mortality but does not affect all cause mortality. (The trial is registered in the ISRCTN registry under number 49127736.)

Background The European Randomized Study of Screening for Prostate Cancer (ERSPC) reported a 29% prostate cancer mortality reduction among screened men after 11 years. However, it is uncertain to what extent harms from overdiagnosis and treatment on quality of life counterbalance this benefit. Methods Based on ERSPC follow-up data, we used micro-simulation modeling (MISCAN) to predict the number of prostate cancers, treatments, deaths and quality-adjusted life-years (QALYs) gained following the introduction of screening. Various screening strategies, efficacies, and quality of life assumptions were modeled. Results Per 1,000 men of all ages followed for their entire lifespan we predicted for annual screening from age 55–69 years: 9 fewer deaths due to prostate cancer (28% reduction), 14 fewer men receiving palliative therapy (35% reduction), and 73 life-years gained (average 8.4 years per prostate cancer death avoided). QALYs gained were 56 (range: −21, 97), a reduction of 23% from unadjusted life-years gained. The number needed to screen (NNS) was 98 and number needed to detect (NND) 5. Also inviting men aged 70–74 resulted in more life-years (82) but similar QALYs (56). Conclusions Although NNS and NND are more favorable than previously calculated, the benefit of PSA screening is diminished by loss of QALYs, that is dependent primarily on post-diagnosis long-term effects. Longer follow-up data from both the ERSPC and quality of life are essential before making universal recommendations regarding screening.