Refining prostate cancer detection: Does MRI‑negative‑zone sampling add value to MRI‑targeted transperineal biopsy?

The role of sampling MRI-negative zones alongside MRI-targeted transperineal (TP) prostate biopsy in MRI-positive men remains debated. We assessed the incremental yield of MRI-negative-zone sampling for clinically significant prostate cancer (csPCa) when added to MRI-targeted TP biopsy, against combined biopsy as the composite reference. Between October 2023 and October 2024, 185 consecutive men with elevated PSA or abnormal digital rectal examination and positive mpMRI (PI-RADS ≥ 3) were assessed; five were excluded, leaving 180. A risk-stratified protocol was used: six targeted cores per MRI-positive zone and four non-targeted cores per MRI-negative zone. Combined biopsy was used as a composite reference, and a sensitivity analysis excluded the 10 men who did not undergo MRI-negative-zone sampling. The PI-RADS subgroup analysis was exploratory. Mean age was 70.4 years; median PSA was 9.3 ng/mL (IQR 6.7–16.8), median PSA density 0.20 ng/mL/cc; 93% had PI-RADS 4 or 5. Combined biopsy detected csPCa in 151/180 (83.9%). MRI-targeted biopsy achieved 96.0% sensitivity for csPCa (95% CI 91.6–98.2%). MRI-negative-zone sampling identified csPCa not found by targeted cores in 6/180 men (3.3%; 95% CI 1.2–7.1%) and accounted for 6/151 csPCa diagnoses (4.0%; 95% CI 1.5–8.4%). Among the 170 men who underwent both components, the incremental yield was 6/170 (3.5%; 95% CI 1.3–7.5%). Within this risk-stratified protocol, MRI-negative-zone sampling added csPCa detection in 3.3% of men and accounted for 4.0% of csPCa diagnoses. The exploratory PI-RADS subgroup estimates were imprecise and did not identify a group in which additional sampling could safely be omitted; combined sampling should remain standard pending prospective validation. Patients should be counselled regarding the residual incremental yield.