Free PSA and Clinically Significant and Fatal Prostate Cancer in the PLCO Screening Trial.

We studied whether adding percent free prostate-specific antigen (%fPSA) to total PSA improves prediction of clinically significant prostate cancer (csPCa) and fatal PCa.

6727 men within the intervention arm of the Prostate, Lung, Colorectal and Ovarian Trial had baseline %fPSA. Of this cohort, 475 had csPCa and 98 had fatal PCa. Cumulative incidence and Cox analyses were conducted to evaluate the association between %fPSA/PSA and csPCa/fatal PCa. Harrell's concordance-index (C-index) evaluated predictive ability. Kaplan-Meier analysis assessed survival.

Median follow-up was 19.7 years, median baseline PSA was 1.19 ng/mL, median %fPSA was 18%. Cumulative incidence of fatal PCa for men with baseline PSA≥2 ng/mL and %fPSA ≤10 was 3.2% and 6.1% at 15 and 25 years, compared to 0.03% and 1.1% for men with %fPSA >25%. In younger men (55-64 yr) with baseline PSA 2-10 ng/mL, C-index improved from 0.56 to 0.60 for csPCa and from 0.53 to 0.64 for fatal PCa with addition of %fPSA. In older men (65-74 yr), C-index improved for csPCa from 0.60 to 0.66, while no improvement in fatal PCa. Adjusting for age, digital rectal exam, family history of PCa, and total PSA, %fPSA was associated with csPCa (HR 1.05, P < .001) per 1% decrease. %fPSA improved prediction of csPCa and fatal PCA for all race groups.

In a large US screening trial, the addition of %fPSA to total PSA in men with baseline PSA ≥2 ng/mL improved prediction of csPCa and fatal PCa. Free PSA should be used to risk-stratify screening and decrease unnecessary prostate biopsies.

The Journal of urology. 2023 Jun 29 [Epub ahead of print]

Kendrick Yim, Chaoran Ma, Sigrid Carlsson, Hans Lilja, Lorelei Mucci, Kathryn Penney, Adam S Kibel, Scott Eggener, Mark A Preston

Division of Urology, Brigham and Women's Hospital, Boston, Massachusetts., Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts., Departments of Surgery (Urology Service) and Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York., Department of Pathology and Laboratory Medicine, Surgery, and Medicine at Memorial Sloan Kettering Cancer, New York, New York., Department of Epidemiology, Harvard T.H Chan School of Public Health, Boston, Massachusetts., Department of Urology, University of Chicago, Chicago, Illinois.