Definition of Outcome-Based Prostate-Specific Antigen (PSA) Thresholds for Advanced Prostate Cancer Risk Prediction

SIMPLE SUMMARY: In this study, we used a well calibrated risk prediction model to define prostate-specific antigen (PSA) thresholds for identifying or excluding advanced prostate cancer (PCa) as an aid to personalize management of the diagnostic workup. PSA concentrations ≤ 4.1 (<65 years old) and ≤3.7 μg/L (≥65 years old) excluded an advanced PCa in patients without glandular inflammation, while PSA > 5.7 (<65) and >6.1 μg/L (≥65) suggested a biopsy referral. In the presence of glandular inflammation, PSA does not provide a valid estimate for risk of advanced cancer since the marker variability is higher and the pre-test probability of PCa is low in this group. The proposed PSA thresholds may allow an individualized approach to the diagnostic workup, assisting patients in making an informed decision. However, patients with asymptomatic prostatitis cannot benefit from the use of this model since they cannot be pre-biopsy identified. ABSTRACT: We defined prostate-specific antigen (PSA) thresholds from a well calibrated risk prediction model for identifying and excluding advanced prostate cancer (PCa). We retrieved 902 biopsied patients with a pre-biopsy PSA determination (Roche assay). A logistic regression model predictive for PCa including the main effects [i.e., PSA, age, histological evidence of glandular inflammation (GI)] was built after testing the accuracy by calibration plots and Hosmer-Lemeshow test for goodness of fit. PSA thresholds were derived by assuming a diagnostic sensitivity of 95% (rule-out) and 80% (rule-in) for overall and advanced/poorly differentiated PCa. In patients without GI, serum PSA concentrations ≤ 4.1 (<65 years old) and ≤3.7 μg/L (≥65 years old) excluded an advanced PCa (defined as Gleason score ≥ 7 at biopsy), with a negative predictive value of 95.1% [95% confidence interval (CI): 83.0–98.7] and 88.8% (CI: 80.2–93.9), respectively, while PSA > 5.7 (<65) and >6.1 μg/L (≥65) should address biopsy referral. In presence of GI, PSA did not provide a valid estimate for risk of advanced cancer because of its higher variability and the low pre-test probability of PCa. The proposed PSA thresholds may support biopsy decision except for patients with asymptomatic prostatitis who cannot be pre-biopsy identified.