Avoiding unnecessary biopsy in suspicious prostate cancer using PRIMARY score ≤3 and PSAD ≤0.2 ng/mL/cm3: a real-world, dual-center study from China

BACKGROUND: Among Chinese men with prostate-specific antigen (PSA) 4-20 ng/mL scheduled for biopsy, <20% harbor clinically significant prostate cancer (csPCa, International Society of Urological Pathology [ISUP] ≥2); most procedures target non-clinically significant prostate cancer (non-csPCa; ISUP <2) or benign prostatic hyperplasia (BPH). We tested whether prostate-specific membrane antigen (PSMA) positron-emission tomography/computed tomography (PET/CT) combined with multiparametric imaging and laboratory assays can accurately identify non-csPCa/BPH and safely reduce unnecessary biopsies. MATERIALS AND METHODS: We retrospectively enrolled patients from two centers. In the discovery cohort, participants underwent PSA testing, mpMRI, and 68Ga-PSMA-PET/CT, and were assessed for Prostate Imaging Reporting and Data System (PI-RADS) and PRIMARY scores. Receiver operating characteristic (ROC) curves, decision curve analysis, and diagnostic tests compared the efficacy of each indicator for non-csPCa/BPH and established the optimal strategy. The validation cohort independently verified this strategy. RESULTS: Discovery cohort (n = 243): PRIMARY score area under the curve (AUC) 0.92 (95% confidence interval [CI]: 0.88-0.95); cutoff ≤3 provided 83.5% sensitivity and 90.9% specificity, outperforming PI-RADS (P = 0.002), PSA density (PSAD), free/total PSA (f/tPSA), and total PSA (tPSA) (all P < 0.0001). Combined models: PRIMARY score + PI-RADS AUC 0.95 (0.92-0.97); PRIMARY + PSAD or + f/tPSA both 0.94. A strategy of PRIMARY score ≤3 plus PSAD ≤0.2 achieved 100% specificity and positive predictive value (PPV) for csPCa, sparing 54.1% of unnecessary biopsies with zero csPCa missed - superior to European Association of Urology (EAU)-recommended PI-RADS ≤2 + PSAD ≤0.2 (sensitivity 19.6%). External cohort (n = 149) validated 100% specificity/PPV, avoiding 69.6% of biopsies while maintaining 0% csPCa miss rate. CONCLUSIONS: In men with suspected prostate cancer (PSA 4-20 ng/mL or abnormal digital rectal examination), the combined criterion of PRIMARY score ≤3 and PSAD ≤0.2 ng/mL/cm3 enabled pre-biopsy triage that safely avoided immediate diagnostic biopsy in more than 50% of patients ultimately found to harbor non-csPCa and BPH in our cohorts, while ensuring that no csPCa was missed. These findings require confirmation in larger prospective, multicenter studies before routine clinical implementation.