JU INSIGHT Free PSA and Clinically Significant and Fatal Prostate Cancer in the PLCO Screening Trial
By: Kendrick Yim, MD, Brigham and Women’s Hospital, Boston, Massachusetts; Chaoran Ma, MD, PhD, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts; Sigrid Carlsson, MD, PhD, MPH, Memorial Sloan Kettering Cancer Center, New York, New York, Sahlgrenska Academy at Gothenburg University, Gothenburg, Sweden; Hans Lilja, MD, PhD, Memorial Sloan Kettering Cancer Center, New York, New York; Lund University, Malmö, Sweden; Lorelei Mucci, ScD, MPH, Harvard T.H. Chan School of Public Health, Boston, Massachusetts; Kathryn Penney, ScD, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, Harvard T.H. Chan School of Public Health, Boston, Massachusetts; Adam S. Kibel, MD, Brigham and Women’s Hospital, Boston, Massachusetts; Scott Eggener, MD, University of Chicago, Illinois; Mark A. Preston, MD, MPH, Brigham and Women’s Hospital, Boston, Massachusetts | Posted on: 25 Oct 2023
Yim K, Ma C, Carlsson S, et al. Free PSA and clinically significant and fatal prostate cancer in the PLCO Screening Trial. J Urol. 2023;10.1097/210(4):630-638.
Study Need and Importance
Questions remain regarding the best PSA screening protocol to maximize capture of clinically significant prostate cancer (csPCa) while minimizing overdiagnosis and overtreatment of indolent disease. Free PSA (fPSA) is readily available, cheap, and has been associated with overall prostate cancer (PCa) diagnosis. We sought to evaluate if a single PSA combined with percent free PSA (%fPSA) would help further risk-stratify men for screening and increase diagnostic accuracy for csPCa and fatal PCa utilizing data from PLCO (Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial).
What We Found
Regardless of age or racial background, addition of %fPSA to total PSA improved prediction of csPCa and fatal PCa in men with a total PSA ≥2 ng/mL. 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, respectively, compared to 0.03% and 1.1% for men with %fPSA >25%. Those with %fPSA ≤10% had significantly worse csPCa and fatal PCa-free survival compared to %fPSA 11%-25% and >25% (see Figure). 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.
Within PLCO, fewer than 20% of men in the intervention arm had a fPSA measured. Initial selection for fPSA drawing was random, but to increase racial diversity, non-White race groups were prioritized for inclusion. Lastly, only a single fPSA value at enrollment was evaluated. There may be additional value with repeat testing.
Interpretation for Patient Care
This is the largest prospective study examining %fPSA and PCa outcomes with long-term follow-up of 20 years. We suggest that fPSA reporting should be expanded to a total PSA of 2-10 ng/mL and also inform risk of csPCa. fPSA should be utilized in risk-stratified PSA screening strategies to help decrease overdiagnosis/overtreatment of indolent PCa and improve identification of those men at highest risk of csPCa.