Confirmation of Prostate-specific Antigen (PSA) Values Improves Prostate Cancer Screening in Early Middle-Aged Men – Data from the PROBASE Trial

BACKGROUND AND OBJECTIVE: To assess the effectiveness of a confirmatory prostate-specific antigen (PSA) test as a safeguard against unnecessary work-up and to improve the specificity of prostate cancer (PCa) screening. METHODS: Overall, 72,157 PSA values corresponding to screening rounds at age 45-55 yr in the PROBASE trial were analyzed. Positive PSA tests were reported as the proportion of men with an initial or confirmatory PSA ≥3 ng/ml. The cumulative PCa number over 6 yr was described for men with and without confirmatory PSA decrease at baseline screening (age 45 yr). Sankey diagrams were plotted to illustrate changes in PSA values over 10 yr with 2-yearly PSA screening. KEY FINDINGS AND LIMITATIONS: Overall, 2782 initial PSAs and 2702 (97%) confirmatory PSAs were observed. A total of 38% (95% confidence interval [CI] 36, 40) of men with initial PSA ≥3 ng/ml had a PSA <3 ng/ml at confirmatory testing. Estimates differed by age and screening round: 46% (95% CI 41, 51) in 45-yr-olds and 34% (95% CI 31, 38) in 50-yr-olds. PSA was repeated at a median of 28 d (interquartile range [IQR] 20, 39). Median change was -0.5 ng/ml (IQR -1.3, +0.06). PCa risk at 6 yr was 33% in those with confirmed PSA and 7.0% in those with PSA decrease at age 45 yr (risk ratio 4.68, CI 2.55, 8.59). The main limitation is incomplete biopsy information. CONCLUSION: PSA elevations in early-middle-aged men are common and PSA should be confirmed before initiating diagnostic work-up in a screening setting. CLINICAL IMPLICATIONS: Repeating PSA before initiating diagnostic work-up reduces immediate further diagnostics.