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

Abstract

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.

Keywords: comparative study; follow‐up; prostate biopsy; prostate cancer; prostate‐specific antigen density.

Fig. 1

Plot illustrating the cumulative incidence of other‐cause death (solid line) and prostate cancer death (dashed line) following a benign systematic TRUS‐guided biopsy result in men with PSA density (PSAD) <0.15 ng/mL/cm³ (blue) and ≥0.15 ng/mL/cm³ (red). Calculations were performed using competing risk functions. (A) Plot showing both competing events. (B) Plot focusing solely on prostate cancer mortality.

Fig. 2

A non‐parametric regression model with locally estimated scatterplot smoothing illustrating the association of PSA density (PSAD) with prostate cancer mortality in men with a benign systematic TRUS‐guided prostate biopsy result. The distribution density plot of PSAD (yellow) is also shown on the second y‐axis on the right.

Fig. 3

Flowchart of the study cohort selection. ASAP, atypical small acinar proliferation; PCa, prostate cancer; PIN, prostatic intraepithelial neoplasia; PSAD, PSA density.