Risk-Adapted Follow-up After Negative MRI-Targeted Biopsy in PI-RADS 3-5 Lesions: A Clinical Cohort Study With Diagnostic Stewardship Modeling.

BACKGROUND

Optimal follow-up after a negative MRI-targeted biopsy in men with PI-RADS 3-5 lesions remains uncertain. Repeat biopsy may detect missed cancers but exposes many patients to unnecessary risk. We aimed to characterize real-world outcomes and develop a risk-adapted framework.

METHODS

We conducted a retrospective cohort study of 86 men with PI-RADS 3-5 lesions and benign index MRI-targeted biopsy. The primary outcome was detection of prostate adenocarcinoma on repeat biopsy or during surgery for benign prostatic obstruction (BPO). Clinically significant prostate cancer (csPCa) was defined as ISUP grade group ≥2. Imaging trajectories, PSMA-PET findings, and management strategies were analyzed. A baseline risk score incorporating PI-RADS 5, PSA density (PSAD), and abnormal digital rectal examination (DRE) was evaluated.

RESULTS

During follow-up, cancer was detected in 4 patients (4.7%): two on repeat biopsy (both ISUP 1) and two incidentally at BPO surgery, including one csPCa. No cancers occurred in PI-RADS 3 lesions. PSMA-PET positivity clustered in PI-RADS 5. A baseline score ≥2 achieved 100% sensitivity and negative predictive value, with specificity of 80.5% (PSAD ≥0.15) and 85.4% (PSAD ≥0.20), potentially avoiding 76.7-81.4% of repeat procedures.

CONCLUSIONS

Cancer detection after a negative MRI-targeted biopsy was uncommon and predominantly low grade. A risk-adapted approach may reduce unnecessary re-biopsies while preserving detection of clinically significant disease. External validation is warranted.

PATIENT SUMMARY: Men with a suspicious prostate MRI lesion (PI-RADS 3-5) but a negative targeted biopsy often worry about missed cancer. In this study, cancer was uncommon and clinically significant disease was rare, with no cancers in PI-RADS 3 lesions. Combining MRI findings with PSA density and digital rectal examination may help identify men who can safely defer repeat biopsy.