A prospective randomized controlled trial comparing target prostate biopsy alone approach vs. target plus standard in naïve patients with positive mpMRI

Background: In the era of mpMRI guided target fusion biopsy (FB), the role of concomitant standard biopsy (SB) in naïve patients still remains under scrutiny. The aim of this study was to compare the detection rate (DR) of clinically significant prostate cancer (csPCa) in biopsy naïve patients with positive mpMRI who underwent FB alone (Arm A) vs FB+SB (Arm B). Secondary objectives were to compare the incidence of complications, the overall PCa DR and the biopsy results with final pathological findings after robotic prostatectomy (RARP). Methods: This is a single center prospective non-inferiority parallel two arms (1:1) randomized control trial (ISRCTN registry number ISRCTN60263108) which took place at San Luigi Gonzaga University Hospital, Orbassano (Turin, Italy) from 4/2019 to 10/2021. Eligible participants were all adults aged<75 years old, biopsy naïve, with serum PSA<15 ng/mL and positive mpMRI (Pi-Rads V.2>3). FB was performed under ultrasound guidance using the BioJet fusion system; four to six target samples were obtained for each index lesion. SB was performed in accordance with the protocol by Rodríguez-Covarrubias. RARP with total anatomical reconstruction was carried out when indicated. DR of PCa and csPCA (Gleason Score >7) were evaluated. Post-biopsy complications according to Clavien-Dindo were recorded. Concordance between biopsy and RARP pathological findings was evaluated. Fisher's Exact test and Mann-Whitney test were applied; furthermore, Logistic Principal Component Analysis (LogPCA) and Pearson's correlation method, in terms of correlation funnel plots, were performed to explore data in a multivariate way. Results: 201 and 193 patients were enrolled in Arm A and B, respectively. csPCa DR was 60.2% vs. 60.6% in Arm A and B respectively (Δ 0.4%; P=0.93); whilst overall PCa DR was 63.7% vs. 71.0% (Δ 7.3%; P=0.12). However, in a target only setting, the addition of SB homolaterally to the index lesion reaching a non-inferior performance compared to the combined sampling (Δ PCa DR 3%). Although the differences of 7.3% in PCa DR, during RARP were registered similar nerve sparing rate (P=0.89), positive surgical margins (P=0.67) and rate of significant upgrading (P=0.12). LogPCA model showed no distinction between the two cohorts; and Pearson's correlation values turned to be between -0.5 and +0.5. In Arm B, the lesion diameter <10 mm is the only predictive variable of positive SB only for PCa (P=0.04), with an additional value +3% for PCa DR. Conclusions: In biopsy naïve patients, FB alone is not inferior to FB+SB in detecting csPCa (Δ csPCa DR 0.4%). Δ 7.3% in overall PCa DR was registered between the two Arms, however the addition of further standard samples homolaterally to mp-MRI index lesion improved the overall PCa DR of FB only sampling (Δ PCa DR 3%). The omission of SB did not influence the post-surgical outcomes in terms of NS approach, PSMr and upgrading/downgrading.