Diagnostic Significance of the Free-to Total Prostate-specific Antigen Ratio in Differentiating Benign and Malignant Prostatic Lesions: A Cross-sectional Study from a Tertiary Care Centre in Thrissur, Kerala, India

Introduction: Prostate cancer is one of the most common malignancies in men. Although Prostate Specific Antigen (PSA) is widely used for screening, its limited specificity leads to overlap between benign and malignant prostatic conditions. The Free-to-Total PSA (F/T PSA) ratio has been proposed to improve diagnostic accuracy and reduce unnecessary biopsies. Aim: To evaluate the significance of the F/T PSA ratio in diagnosing prostatic pathologies in patients undergoing prostate biopsy. Materials and Methods: This hospital-based cross-sectional study was conducted at the Department of Pathology, Government Medical College, Thrissur, Kerala, India, over a period of 12 months from January 2025 to December 2025 and included 69 patients undergoing prostate biopsy. Serum free and total PSA levels were measured before biopsy, and the F/T PSA ratio was calculated. Histopathological diagnosis and grading were performed. Statistical analysis was conducted using Statistical Package for the Social Sciences (SPSS) software version 25.0, including non parametric tests and Receiver Operating Characteristic (ROC) curve analysis. Diagnostic performance of the F/T PSA ratio, sensitivity and specificity, Positive Predictive Value (PPV), Negative Predictive Value (NPV), logistic regression, and correlation were calculated between PSA parameters and tumour grade. Results: Of 69 cases, 44 (63.8%) were malignant, and 25 (36.2%) were benign. Median age was higher in the malignant group (73 vs. 68 years; p=0.323). Median free PSA (5.1 vs. 3.5 ng/mL; p=0.029) and total PSA (331.5 vs. 9.6 ng/mL; p<0.001) were significantly higher in malignant cases, whereas the F/T PSA ratio was significantly lower (0.0337 vs. 0.3286; p<0.001). ROC analysis showed excellent diagnostic performance of the F/T PSA ratio (AUC: 0.929; 95% CI: 0.868-0.990; p<0.001). At a cut-off ≤0.177, sensitivity and specificity were 88.6% and 88.0%, with PPV 92.9%, NPV 81.5%, and overall accuracy 88.4%. 39 (88.6%) of malignant cases had an F/T PSA ratio ≤0.177, while 88.0% of benign cases had values above the cut-off (p<0.001). Logistic regression identified F/T PSA ≤0.177 as a strong, significant predictor of malignancy (odds ratio: 57.2; 95% CI: 12.46–262.52; p<0.001). Spearman correlation analysis revealed no significant correlations between Gleason score or grade group and free PSA, total PSA, or F/T PSA ratio (all p>0.05). Conclusion: The F/T PSA ratio is a valuable diagnostic adjunct for distinguishing malignant from benign prostatic lesions. However, the F/T PSA ratio did not correlate with tumour grade, and histopathological examination with Gleason grading remains essential for assessment of tumour aggressiveness and prognosis.