Extended mortality results for prostate cancer screening in the PLCO trial with median follow‐up of 15 years

Abstract

Background Two large-scale prostate cancer screening trials with prostate-specific antigen (PSA) have given conflicting results in terms of the efficacy of such screening. One of those trials, the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial, previously reported outcomes through 13 years of follow-up. Here we present updated findings from PLCO. Methods PLCO randomized subjects from 1993–2001 to an intervention or control arm. Intervention arm men received annual PSA tests for six years and digital rectal exam for four years. We used linkage with the National Death Index (NDI) to extend mortality follow-up to a maximum of 19 years from randomization. Results 38,340 and 38,343 men were randomized to the intervention and control arms, respectively. Median (25th/75th) follow-up time was 14.8 years (12.7/16.5) in the intervention and 14.7 years (12.6/16.4) in the control arm. 255 (intervention arm) versus 244 (control arm) deaths from prostate cancer were observed, for a rate-ratio (RR) of 1.04 (95% CI: 0.87–1.24). The RR for all-cause mortality was 0.977 (95% CI: 0.950,1.004). An estimated 86% of control versus 99% of intervention arm men received any PSA testing during the trial, with estimated yearly screening phase PSA testing rates of 46% (control) versus 84% (intervention). Conclusion Extended follow-up of PLCO over a median of 15 years continues to indicate no reduction in prostate cancer mortality for the intervention compared to control arms. Due to the high rate of control arm PSA testing, this finding can be viewed as showing no benefit of organized over opportunistic screening.

Reconciling the Effects of Screening on Prostate Cancer Mortality in the ERSPC and PLCO Trials

“…However, the trials produced apparently conflicting results, with the ERSPC reporting a 21% reduction in prostate cancer mortality (4–6) and the PLCO finding no mortality difference between the trial arms (7–9). Interpreting results of these trials is complicated by differences in their implementations, including design and adherence, and practice settings.…”

Reconciling the Effects of Screening on Prostate Cancer Mortality in the ERSPC and PLCO Trials

“…However, the trials produced apparently conflicting results, with the ERSPC reporting a 21% reduction in prostate cancer mortality (4)(5)(6) and the PLCO finding no mortality difference between the trial arms (7)(8)(9). Interpreting results of these trials is complicated by differences in their implementations, including design and adherence, and practice settings.…”

“…The US practice setting also contributed to a higher frequency of screening in the control arm and a lower frequency of biopsy compared with the ERSPC. Consequently, the PLCO compared effects of an organized screening program relative to opportunistic screening rather than effects of screening versus no screening (8)(9)(10). Nonetheless, the PLCO results have been viewed as more relevant to the US setting (11).…”

Canadian Urological Association recommendations on prostate cancer screening and early diagnosis

“…11 The PCLO was a North American trial including 76 683 men aged 55-74 accrued from 10 centres where subjects were randomized to organized screening or standard care. 9 In the recently published update, with 15 years of followup, there continues to be no difference in prostate cancer-specific mortality between patients in the intervention (screening) and control arms; 15 however, several important limitations may mitigate this finding. Foremost, there was considerable contamination between study arms, with over 80% of subjects in the control arm having at least one PSA measurement during the study period.…”