Predicting Long-Term Risk for Prostate Cancer Mortality Following a Prostate-Specific Antigen Screening Test: Prognostic Model Development and External Validation.

Authors

Lewicki P, Jiang R, Radhakrishnan A, Bryant A, Schipper M, Morgan TM, Stensland K

Affiliations

• Department of Urology, University of Michigan, Ann Arbor, Michigan (P.L., T.M.M.).
• Department of Biostatistics, University of Michigan, Ann Arbor, Michigan (R.J.).
• Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan (A.R.).
• Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (A.B.).
• Department of Biostatistics and Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (M.S.).
• Department of Urology and Department of Learning Health Sciences, University of Michigan, Ann Arbor, Michigan (K.S.).

Abstract

BACKGROUND: Despite the scale of prostate-specific antigen (PSA) testing for prostate cancer (PCa) screening, prediction models do not predict time-to-event end points or adjust for patient life expectancy.

OBJECTIVE: To develop, externally validate, and compare to existing tools a novel prognostic model for risk for prostate cancer-specific mortality (PCSM) after a PSA test.

DESIGN: Prognostic model development in the PCa screening group of the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial; external validation in a Veterans Affairs (VA) population of patients undergoing PSA testing.

SETTING: United States. PLCO patients were enrolled from 1993 to 2001, and VA patients underwent PSA testing from 2002 to 2006. Survival follow-up was updated through 2022 in both cohorts.

PATIENTS: Male patients aged 55 to 74 years in the PLCO PCa screening group (n = 33 339) and the VA Healthcare System (n = 174 787).

MEASUREMENTS: The model's predicted outcome is PCSM at a specified time point; predictors included PSA level, family history of PCa, and race. Predictors of other-cause mortality included age; body mass index; smoking status; and presence of hypertension, diabetes, or stroke.

RESULTS: In the model development cohort, the area under the receiver operating characteristic curve (AUC) at 29.5 years from screening was 0.666 compared with 0.643 for a previously validated prostate biopsy risk model (Prostate Biopsy Collaborative Group [PBCG]) (P < 0.001). In the external validation cohort, the AUC at 20 years from screening was 0.776 for the PLCO model versus 0.749 for the PBCG model (P = 0.031).

LIMITATION: The model may not be generalizable to more contemporary PSA screening practices given the periods studied.

CONCLUSION: This PCSM prognostic model was developed from long-term clinical trial data, was externally validated in a large national cohort, and may be used to improve interpretation of PSA results.

PRIMARY FUNDING SOURCE: None.