Whole-gland or Subtotal High-intensity Focused Ultrasound Versus Radical Prostatectomy: The Prospective, Noninferiority, Nonrandomized HIFI Trial.

Background And Objective: High-intensity focused ultrasound (HIFU) has emerged as an interesting ablative alternative to radical prostatectomy (RP) and radiation therapy (RT) for localized prostate cancer (PC). However, no prospective comparative data have been published for HIFU.

Methods: We performed a prospective nonrandomized nationwide trial in 46 centers in France comparing RP versus HIFU. The main inclusion criterion was low- to intermediate-risk PC. The primary endpoint was salvage therapy-free survival (STFS). Secondary endpoints were metastasis-free survival, PC-specific survival, overall survival, and functional outcomes.

Key Findings And Limitations: From 2015 to 2019, 3328 patients were included (1967 HIFU and 1361 RP). Median age was 74.7 versus 65.1 yr (p < 0.001) and median PSA was 7.1 versus 6.9 ng/ml (p = 0.5) in the HIFU and RP groups, respectively. Intermediate-risk PC was diagnosed in 61% of patients in the HIFU group and 64% in the RP group (p = 0.10). The 30-mo STFS was not inferior in the HIFU group (hazard ratio 0.71, 95% confidence interval 0.52-0.97; p = 0.008). Some 10% of patients experienced urinary retention after HIFU. Grade >IIIa complications occurred in 54/1967 cases in the HIFU group and 29/1361 cases in the RP group (p = 0.3). In the HIFU group, fewer patients experienced a deterioration in 12-mo urinary continence (29% vs 44%) and the decrease in median International Index of Erectile Function-5 score was lower (difference -7 vs -13) in comparison to RP. Internal Prostate Symptom Scores and quality-of-life scores were comparable in the two groups. The main limitations are the lack of randomization and the age difference between the groups.

Conclusions And Clinical Implications: This large prospective trial demonstrates that whole-gland or subtotal HIFU provides comparable medium-term STFS outcomes to RP. Urinary continence and erectile function were less impaired after HIFU. These results should be interpreted with caution owing to the lack of randomization and the age difference between the groups. Future research should consider longer follow-up and evaluate focal treatments. This trial is registered on ClinicalTrials.gov as NCT04307056.