DIAGNOSTIC ACCURACY OF PROSTATE-SPECIFIC ANTIGEN DENSITY, FREE-TO-TOTAL PSA RATIO, AND DIGITAL RECTAL EXAMINATION IN DETECTING PROSTATE CANCER AMONG MEN WITH SERUM PSA LEVELS IN THE GRAY ZONE (4–10 NG/ML): A PROSPECTIVE OBSERVATIONAL STUDY

Abstract

Objective

To determine the diagnostic accuracy of prostate-specific antigen density (PSAD), free-to-total PSA ratio (f/t PSA), and digital rectal examination (DRE) for detecting prostate cancer among men with serum PSA levels in the diagnostic gray zone (4–10 ng/mL).

Methodology

This prospective observational study was conducted in the Department of Urology of a tertiary-care teaching hospital in Pakistan. One hundred and thirty-two consecutive men with total serum PSA 4–10 ng/mL underwent clinical evaluation, digital rectal examination, transrectal ultrasonography for prostate volume estimation, and ultrasound-guided transrectal 12-core prostate biopsy. PSA density was calculated as total PSA divided by prostate volume. Histopathology was the reference standard. Continuous variables were compared using the Mann-Whitney U test or independent t-test and categorical variables using the chi-square or Fisher’s exact test. Independent predictors of prostate cancer were identified using multivariable binary logistic regression, with adjusted odds ratios (OR) and 95% confidence intervals (CI) reported. A two-tailed p<0.05 was considered significant.

Results

Prostate cancer was confirmed in 27/132 patients (20.5%). Patients with cancer were significantly older than those without (median 70 vs 64 years, p=0.011) and had smaller prostate volumes (41.4±11.2 vs 60.3±21.1 mL, p<0.001) and higher PSAD (0.19 vs 0.13 ng/mL/cm³, p<0.001). Free PSA and f/t PSA ratio were significantly lower among cancer patients (both p<0.001). Total PSA did not differ significantly between groups (8.3 vs 7.9 ng/mL, p=0.410), and DRE positivity, although more frequent in the cancer group (14.8% vs 5.7%), did not reach significance (p=0.121). On multivariable logistic regression, age (OR 1.07, 95% CI 1.01–1.14, p=0.030) and PSAD (OR per unit increase 3.4×10⁵, 95% CI 512–2.3×10⁸, p<0.001) were independent predictors of prostate cancer, whereas total PSA was not (OR 0.96, p=0.745). Among the 27 cancer patients, 16 (59.3%) had clinically significant disease (Gleason score ≥7); the percentage of positive biopsy cores independently predicted clinically significant cancer (OR 1.08 per 1% increase, 95% CI 1.02–1.14, p=0.007).

Conclusion

PSA density was the strongest independent predictor of prostate cancer among men with gray-zone PSA values, while total PSA alone showed limited discriminatory value. Incorporating PSAD, together with age, free PSA/f-t-PSA ratio, and digital rectal examination, into routine assessment may improve patient selection for prostate biopsy and reduce unnecessary invasive procedures, particularly in resource-limited settings.