Development and Validation of a Novel Indicator for Differential Diagnosis of Clinically Significant Prostate Cancer...

Objective: This study aims to explore new hematological indicators with differential diagnostic significance for clinically significant prostate cancer (csPCa) by conducting comprehensive hematological tests, and to construct a novel discrimination index (DI) (csPCa-DI) to improve the diagnostic accuracy of csPCa. Methods: A total of 542 patients suspected of prostate cancer who were admitted to Beijing Tsinghua Changgung Hospital from November 2014 to May 2025 were enrolled in this study. All patients underwent complete blood count, coagulation testing, full biochemical analysis, and prostate biopsy. According to the biopsy results, patients were divided into the csPCa group and the non-csPCa group. The differences in hematological indicators between the two groups were compared, and multivariate logistic regression analysis was used to screen independent risk factors for csPCa. Two scoring systems (Fib-PLT Score and Fib-PLT-DD Score) were constructed based on coagulation-related parameters, and a csPCa discrimination index (csPCa-DI) was further established by integrating independent risk factors. The diagnostic efficacy of these scores, csPCa-DI, and traditional PSA-related indicators was evaluated by receiver operating characteristic (ROC) curves. Stratified validation was performed in the PSA gray zone (4-10 ng/mL) population. Results: Multivariate logistic regression identified prostate-specific antigen density (PSAD) (OR = 18.063, 95% CI: 7.125-45.792, p < 0.001), age (OR = 1.062, 95% CI: 1.024-1.102, p = 0.001), and Fib-PLT-DD Score (OR = 0.388, 95% CI: 0.251-0.599, p < 0.001) as independent predictors of csPCa. Based on the regression coefficient (β) weights of the independent predictors, the csPCa-DI was formulated as: csPCa-DI = 2.894 × PSAD + 0.060 × Age - 0.946 × Fib-PLT-DD Score (Fib-PLT-DD Score = 0.672 × Fib + 0.008 × PLT - 0.028 × DD). In the overall cohort, the area under the ROC curve (AUC) of csPCa-DI for diagnosing csPCa was 0.821 (95% CI: 0.773-0.868, p < 0.001), higher than that of total PSA (0.701) and f/t PSA ratio (0.727), and slightly higher than PSAD (0.797). The optimal cut-off value of csPCa-DI in the overall cohort was 1.46 points, with a sensitivity of 87.4% and specificity of 61.8%. In the PSA gray zone population, csPCa-DI exhibited superior diagnostic efficacy with an AUC of 0.736 (95% CI: 0.634-0.838, p < 0.001), significantly higher than total PSA (0.465) and f/t PSA ratio (0.638), and slightly higher than PSAD (0.720). A csPCa-DI cut-off value of 0.92 points in the PSA gray zone achieved a high sensitivity of 96.0% (specificity = 48.0%), effectively reducing missed diagnosis, while the cut-off of 1.46 points balanced sensitivity (68.0%) and specificity (70.7%). Conclusions: The novel csPCa-DI constructed by integrating PSAD, age, and coagulation-derived Fib-PLT-DD Score based on β weights has higher diagnostic efficacy for csPCa than traditional single PSA-related parameters, especially in the PSA gray zone, which can provide a new clinical tool for the screening and differential diagnosis of csPCa. This study also clarifies the correlation between local coagulation abnormalities and csPCa, providing a new perspective for understanding the pathological mechanism of csPCa.