Focal Therapy Using High-Intensity Focused Ultrasound for Low- and Intermediate-Risk Prostate Cancer: Results from a Prospective, Multicenter Feasibility Trial

Background/Objectives: Whole-gland surgery or radiotherapy for localized prostate cancer (PCa) can cure the disease but often impair urinary and sexual function. Focal therapy with high-intensity focused ultrasound (HIFU) seeks to eradicate the tumor while sparing uninvolved tissue. We prospectively evaluated oncological control, functional outcomes and safety of MRI-guided focal HIFU in patients with low- or intermediate-risk PCa. Methods: In this prospective, single-arm, phase II feasibility trial (three Austrian centres, 2021–2024), treatment-naive patients with D’Amico low/intermediate-risk, PSA ≤ 15 ng/mL, clinical stage ≤ T2 and MRI-targeted, biopsy-confirmed index lesions underwent lesion-targeted HIFU (Focal One™). The primary endpoint was failure-free survival (FFS: absence of salvage whole-gland or systemic therapy, metastasis or PCa-specific death). Secondary endpoints included biopsy-proven cancer, prostate-specific antigen (PSA), patient-reported symptoms as International Prostate Symptom Score (IPSS), 5-item International Index of Erectile Function (IIEF), Gaudenz Incontinence Questionnaire and adverse events. Planned follow-up was 24 months with PSA every 3 months, mpMRI and biopsies at 12 months, and imaging- or PSA-triggered biopsies thereafter. Results: Fifty-one men were analysed in the per-protocol cohort (median age 67 years, median PSA 7.55 ng/mL). Median treated volume was 12 mL; median procedure time 85 min. At 24 months, FFS was 94.1%: 3/51 patients (5.9%) required salvage radiotherapy. Among 31 patients who underwent follow-up biopsy, 26 (83.9%) had no cancer; the five positives included three ISUP 1, one ISUP2 and one ISUP 4 lesion. Mean PSA fell by 69% at 3 months (to 2.3 ng/mL) and then stabilized under 3 ng/mL, with a mean of 2.7 ± 1.5 ng/mL at 24 months. Transient acute urinary retention occurred in 11/51 (21.6%); no Clavien–Dindo grade ≥ 4 events were reported. IPSS returned to or improved beyond baseline, erectile function largely recovered by 6–12 months, and only one new case of grade 2 incontinence was observed. Conclusions: MRI-guided focal HIFU achieved high two-year failure-free survival with low morbidity and preserved quality of life in carefully selected patients with low- or intermediate-risk PCa. These data support further randomized and longer-term investigations of focal HIFU as an organ-sparing alternative to whole-gland treatment.