Toward a PSMA PET–mpMRI pathway for biopsy decision-making in men with suspected prostate cancer: interim results from the prospective BIOPSTAGE trial

INTRODUCTION: The BIOPSTAGE trial investigates the added diagnostic value of combining prostate-specific membrane antigen positron emission tomography (PSMA PET) with multiparametric MRI (mpMRI) for non-invasive detection of clinically significant prostate cancer (csPCa). This interim analysis aimed to retrospectively optimize semiquantitative PSMA PET thresholds and evaluate potential biopsy reduction through integrated imaging. METHODS: In this prospective, single-institution study, 96 men with suspected prostate cancer underwent mpMRI and PSMA PET prior to biopsy. csPCa was defined as ISUP grade group ≥2. Receiver operating characteristic (ROC) analysis identified optimal thresholds for SUVmax (≥9.1) and SUVratio (≥3.6). Diagnostic performance metrics (sensitivity, specificity, predictive values, and biopsy burden) were evaluated for mpMRI, PSMA PET, and their combination. Logistic regression and McNemar's test assessed predictors and comparative accuracy. RESULTS: mpMRI alone achieved a sensitivity of 93.8%, specificity of 54.6%, and an AUC of 0.74. Among the 74 lesions identified by mpMRI, 14 also met semiquantitative PET positivity criteria. An additional 11 PET-positive lesions were detected without corresponding mpMRI abnormalities. Another 60 lesions were mpMRI-positive but PET-negative and would not have been targeted in an integrated strategy. If biopsy had been guided exclusively by PSMA PET-positive lesions, 25 targets would have been sampled-representing an approximately 66.2% reduction compared to 74 lesions identified by mpMRI alone. This biopsy reduction was associated with significantly improved specificity (McNemar's p < 0.001). Integrated imaging diagnostic accuracy was: sensitivity 85.7% (95% CI: 60.1-96.0%), specificity 86.3% (95% CI: 78.0-91.8%), PPV 48.0%, NPV 97.6%. Two small csPCa lesions missed by PSMA PET were PI-RADS 4, ISUP Grade Group 2. One csPCa lesion detected exclusively by PSMA PET was not visible on mpMRI (ISUP Grade Group 3). CONCLUSIONS: Integrating semiquantitative PSMA PET with mpMRI improves lesion-level specificity and was associated with a theoretical reduction of approximately two-thirds in the number of targeted biopsy cores, while maintaining high sensitivity. While PSMA PET enhances risk stratification, mpMRI remains essential-particularly for detecting small or PSMA-negative tumors. These interim findings support feasibility of a dual-imaging biopsy triage strategy, pending validation in the full BIOPSTAGE cohort and future multicenter trials.