Randomized controlled screening trials for prostate cancer using prostate-specific antigen: a tale of contrasts

Abstract

This article aims to review the merits of the use of prostate-specific antigen (PSA) as a screening tool in the detection of prostate cancer and the evidence presented by the US and European population-based, randomized controlled trials evaluating screening. Many studies have attempted to ascertain whether PSA screening is beneficial with respect to cancer-specific mortality. This report aims to clarify the issues specific to the PSA test, prostate cancer, sources of bias, and the future of screening. We performed an Ovid-Medline literature search for articles pertaining to the introduction of the PSA test, its use for screening for prostate cancer, confounders and biases specific to PSA and prostate cancer's natural history, and reports specific to the Prostate, Lung, Colon, and Ovarian Cancer Screening Trial (PLCO), and the European Randomized Study of Screening for Prostate Cancer (ERSPC). We reviewed these articles and present relevant data. PSA emerged as one of the most-used serum tests to screen for cancer, particularly in the US, but in Europe as well. The PLCO trial showed no benefit to screening, and the ERSPC showed a 20% relative risk reduction of cancer-specific mortality. This translated to an absolute reduction of PCa-related deaths of 0.71 per 1,000. Each trial has criticisms that may or may not have affected power and outcome, although the rate ratios comparing screening to not screening are similar. Definitive evidence for or against screening is still lacking, as interim analyses from the ERSPC and PLCO await further follow-up in the years to come.