A head-to-head comparison of sextant-systematic biopsy versus extended-systematic biopsy for prostate cancer diagnosis in the era of MRI-targeted biopsy: Non-inferiority randomized clinical trial.

5120 Background: In recent years, combined targeted biopsy (TB) and 12-core extended systematic biopsy (SB) (TB+12SB) has been recommended for biopsy-naïve patients with prostate MRI-visible lesions. However, increasing SB cores elevates complication risks and healthcare expenditure. Retrospective data indicated noninferior PCa detection with TB + sextant-SB (TB+6SB) vs TB+12SB. This RCT aims to compare the novel TB+6SB scheme and classical TB+12SB for PCa diagnosis. Methods: In this non-inferiority RCT (NCT06684652), 506 biopsy-naïve men with solitary mpMRI lesions (PI-RADS ≥3) underwent transperineal cognitive fusion 3-core TB within the predefined mpMRI index lesion (ROI), followed by randomization to 12-core SB or 6-core sextant SB (2 peripheral+1 transitional cores/side). The primary outcome was clinically significant PCa [csPCa, grade group (GG) ≥2] detection rate. Non-inferiority was established if the lower 95% CI bound for the rate difference exceeded -15%. Results: Baseline characteristics were similar. TB+6SB demonstrated noninferior csPCa detection versus TB+12SB [54.3% (138/254) vs. 54.8% (138/252); rate difference -0.5%, 95%CI -9.2%-8.3%]. Comparable detection was also observed in PCa, high-grade PCa (GG≥3), and clinically insignificant PCa (GG=1). The concordance in GG between biopsy and radical prostatectomy whole-mount specimens was similar for both TB+12SB [52.3% (34/65), κ=0.55] and TB+6SB [51.7% (30/58), κ=0.50] groups (p=0.25). TB+6SB showed superior safety profiles, significantly relieving the procedural discomfort, reducing the post-biopsy pelvic pain, and improving the quality of life (p<0.05). The biopsy time of TB+6SB was significantly shorter than that of TB+12SB (p<0.001). Conclusions: TB+6SB achieves non-inferior diagnostic efficacy to classical TB+12SB with fewer cores and improved safety, positioning it as an effective strategy for PCa diagnosis in biopsy-naïve patients with solitary MRI-suspicious lesions. TB+6SB could improve operational efficiency, providing both clinical safety and cost-effectiveness in histopathological workflows. Clinical trial information: NCT06684652 . Clinicopathological characteristics after biopsy. Characteristics TB+12SB (n=252) TB+6SB (n=254) P value csPCa (%) 138 (54.8) 138 (54.3) 1 RD (95%CI) -0.5% (-9.2%, 8.3%) High-grade PCa (%) 72 (28.6) 74 (29.1) 1 Number of biopsy cores (per case) 15.0 9.0 Proportion of positive cores (%) (median [IQR]) 20.0 [0, 46.7] 33.3 [0, 55.6] 0.02 Procedural time (second) (median [IQR]) 234.0 [220.0, 258.3] 167.5 [154.0, 187.0] <0.001 Cost of pathological examination ($) (per case) 75.0 50.0 - Pain level (VAS) (median [IQR]) 3.0 [2.0, 4.0] 2.0 [2.0, 4.0] 0.004 Discomfort level (median [IQR]) 3.0 [3.0, 5.0] 3.0 [1.5, 4.0] 0.03 OABSS total score after biopsy (median [IQR]) 3.0 [2.0, 7.0] 3.0 [2.0, 5.0] 0.02