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

Background: In recent years, combined MRI-targeted biopsy (TB) and 12-core extended systematic biopsy (SB) (TB + 12SB) has been recommended for biopsy-naïve patients with MRI-visible lesions for prostate cancer (PCa) diagnosis. However, extended biopsy increases complication burden and healthcare expenditure. This head-to-head RCT aims to compare the novel combined MRI-TB and sextant six-core SB (TB + 6SB) scheme and classical TB + 12SB for PCa diagnosis. Methods: From December 2024 to June 2025, this single-center non-inferiority RCT (NCT06684652) consecutively enrolled 506 biopsy-naïve men with single suspicious lesion on prostate mpMRI. Patients were randomized to undergo TB + 12SB (n = 252) or TB + 6SB (n = 254) through transperineal cognitive fusion technique. The study outcome included clinically significant PCa [csPCa, grade group (GG) ≥2, primary outcome], diagnostic accuracy, complication rates, and health economic profiles. Findings: The baseline characteristics were similar. The csPCa detection rate of TB + 6SB [54.3%, 138/254] was non-inferior to that of TB + 12SB [54.8%, (138/252)] [rate difference and 95% confidence interval: -0.5% (-9.2%, 8.3%)]. Comparable detection was also observed in PCa, high-grade PCa, and clinically insignificant PCa. 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 demonstrated superior safety profiles through significantly relieving the discomfort during the procedure, reducing the post-biopsy pelvic pain, and significantly improving the quality of life (p < 0.05), while concurrently optimizing procedural workflow efficiency and histopathology resource utilization. Interpretation: TB + 6SB achieves non-inferior diagnostic efficacy to classical TB + 12SB with reduced cores and improved safety, positioning it as an effective strategy for PCa diagnosis in biopsy-naïve patients with solitary MRI-suspicious lesions. Funding: Beijing Research Ward Excellence Program (BRWEP2024W054070105), National High Level Hospital Clinical Research Funding (Interdepartmental Research Project of Peking University First Hospital, 2023IR27, 2024IR16).