Improving Diagnostic Accuracy for Prostate Cancer in the PSA Grey Zone: A Combined Analysis of PSA-related Parameters and Inflammatory Markers

Prostate cancer (PCa) is a leading cause of cancer-related morbidity and mortality among men globally. Prostate-specific antigen (PSA) testing, though widely used for PCa screening, has low specificity in the “grey zone” (PSA 4.0–10.0 ng/mL), leading to unnecessary biopsies. This study aimed to evaluate whether combining PSA-related parameters with systemic inflammatory markers could improve diagnostic accuracy for PCa within this range. This retrospective study included 37 patients with PSA levels between 4.0 and 10.0 ng/mL who underwent ultrasound-guided prostate biopsy. Laboratory values including total PSA, free PSA, PSA density (PSAD), free-to-total PSA ratio (f/tPSA), and inflammation indices—neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), and platelet-to-lymphocyte ratio (PLR)—were analyzed. The diagnostic performance of these markers and their combinations was assessed using receiver operating characteristic (ROC) curve analysis. Among PSA-related parameters, the novel (f/tPSA)/PSAD index showed the highest diagnostic accuracy (AUC = 0.8515), outperforming PSAD and PSA-AV. Inflammatory markers alone (NLR, MLR, PLR) showed limited diagnostic value. However, the combination of (f/tPSA)/PSAD and NLR significantly improved diagnostic performance (AUC = 0.8909), especially by increasing the negative predictive value (NPV to 80.00%) and positive predictive value (PPV to 86.36%). The (f/tPSA)/PSAD index demonstrates superior diagnostic performance for PCa in patients with PSA levels in the grey zone. When combined with NLR, this parameter further enhances diagnostic efficacy, particularly in reducing false negatives. These findings may help guide clinical decision-making and reduce unnecessary biopsies. Further large-scale, prospective studies are warranted to validate these results.