Association of prostate-specific antigen density with prostate cancer mortality after a benign systematic prostate biopsy result

Objective: To assess the association between prostate-specific antigen (PSA) density (PSAD) and prostate cancer mortality after a benign result on systematic transrectal ultrasonography (TRUS)-guided prostate biopsy. Patients and Methods: This retrospective study used data from the Finnish Randomised Study of Screening for Prostate Cancer (FinRSPC) collected between 1996 and 2020. We identified men aged 55–71 years randomised to the screening arm with PSA ≥4.0 ng/mL and a benign systematic TRUS-guided biopsy result. The cumulative prostate cancer mortality of men stratified by a PSAD cutoff of 0.15 ng/mL/cm³ was modelled with competing risk functions. The ability of PSAD, PSA, and base variables (age at biopsy, DRE result, socioeconomic status, 5α-reductase inhibitor usage, family history, and Charlson Comorbidity Index (CCI)) to predict prostate cancer death was compared using c-statistics and a likelihood ratio test. Results: After excluding 10 men without PSA data within 2 years of the biopsy and 65 without prostate volume data, 2276 men were eligible for inclusion in the study. A total of 50 men died from prostate cancer and 1028 from other causes during a median (interquartile range) follow-up of 17.4 (13.2–20.9) years. The cumulative prostate cancer mortality of men with PSAD <0.15 ng/mL/cm³ was significantly lower than that of men with PSAD ≥0.15 ng/mL/cm³: 0.5% (95% confidence interval [CI] 0.2%–1.1%) vs 2.0% (95% CI 1.2%–3.1%) at 15 years (Grey's test, P = 0.001). The model consisting of PSAD, PSA and the base variables predicted prostate cancer mortality (c-statistic 0.781) significantly better than either the base variables alone (c-statistic 0.737; likelihood-ratio test, P = 0.003) or the base variables and PSA (c-statistic 0.765; likelihood-ratio test, P = 0.039). Conclusion: Prostate cancer mortality after a benign systematic TRUS-guided biopsy is low. In these patients, PSAD predicts prostate cancer mortality and provides additional value to other clinical variables. PSAD-based stratification can be used to guide follow-up strategy.