Development and internal validation of a clinical model to increase the diagnostic probability of prostate cancer in patients with prostate-specific antigen levels of 4.0-10.0 ng/mL

Background: We constructed a diagnostic model to distinguish prostate cancer (PCa) from benign prostatic hyperplasia (BPH) in patients with prostate-specific antigen (PSA) ranging 4.0 to 10.0 ng/ml.

Methods: This retrospective study recruited consecutive458 participants from January 2017 to September 2019. Eligible patients had PSA levels between 4.0-10.0 ng/mL and underwent prostate biopsy or surgery with histopathological confirmation of PCa or BPH by two independent pathologists. Candidate predictors included age, PSA, free PSA (FPSA), F/T ratio, prostate volume (PV), PSAD, white blood cell (WBC), neutrophil (NE), lymphocyte (LY), hemoglobin (HB), platelet (PLT), alanine aminotransferase (ALT), aspartate transaminase (AST), total protein (TP), albumin (ALB), globulin (GLB), creatinine (CREA), urea nitrogen (UREA), and phosphorus (PHOS). Multivariable logistic regression was applied to screen independent risk factors, with bootstrap resampling for internal validation. Model discrimination, calibration and clinical net benefit were assessed via receiver operating characteristic (ROC) curves, calibration plots and decision curve analysis (DCA).

Results: Among 458 patients (192 with PCa, 266 with BPH), the PCa group had significantly higher PSA, PSA density (PSAD), aspartate transaminase (AST), total protein (TP), albumin (ALB), globulin (GLB) and phosphorus (PHOS), but lower FPSA, F/T ratio and prostate volume (PV) (all P<0.05). Age showed marginal significance (P=0.073) and was entered into the regression according to the P<0.1 screening standard. Age, PSA, FPSA, PV, AST, GLB and PHOS were independent PCa predictors. The model’s area under the curve (AUC) was 0.834 (95% confidence interval (CI): 0.799–0.867), with optimism-corrected C-index 0.832 (95% CI: 0.796–0.869). Calibration (calibration: 0.92; Hosmer-Lemeshow test P=0.487) and DCA confirmed stable performance and clinical utility. At the Youden-index cutoff of 0.503, sensitivity reached 69.79% (95% CI: 62.7-76.2%), specificity 80.83% (95% CI: 75.5-85.4%)

Conclusions: This clinical model shows promise for identifying PCa risk in patients with PSA 4.0-10.0 ng/mL; however, external validation in independent cohorts is needed before clinical implementation.