Salvage High-intensity Focused Ultrasound for Prostate Cancer Recurrence after Radiotherapy (HIFI-2 Study).

BACKGROUND AND OBJECTIVE: Management of local prostate cancer (PCa) recurrence after primary radiotherapy (RT) remains challenging in daily practice. Salvage high-intensity focused ultrasound (S-HIFU) represents a valid option, but large prospective data are missing. METHODS: A prospective, nationwide study was conducted in 32 French centers assessing S-HIFU as a local treatment after RT failure in patients with biopsy-confirmed intraprostatic recurrence without regional or distant metastases. The primary endpoint was androgen deprivation therapy-free survival (ADT-FS). Secondary endpoints were PCa-specific survival and overall survival, and functional outcomes. KEY FINDINGS AND LIMITATIONS: From 2015 to 2019, 531 patients were included. Median age and prostate-specific antigen (PSA) at S-HIFU were 75 yr and 4.5 ng/ml, respectively. Median PSA was 0.7 and 1.02 ng/ml at 12 and 30 mo after HIFU, respectively. The 30-mo ADT-FS was 71% in the overall cohort (95% CI, 67-76). A pre-S-HIFU PSA level ≤ 4.5 ng/ml and Gleason score 6-7 had the most favorable ADT- FS rates at 30-mo: 84% (95% CI, 78-91). High-grade (>IIIa) complications graded with the Dindo-Clavien classification were reported in 19/531 patients. The number of cases with severe incontinence increased from 7% to 12% after S-HIFU. The quality-of-life study showed no deterioration in the EORTC QLQC-30 median score at 12 mo. CONCLUSION AND CLINICAL IMPLICATIONS: This large prospective trial demonstrates good oncologic and functional outcomes after S-HIFU for treating local PCa recurrence after RT. The importance of pre-S-HIFU PSA for efficacy prediction highlights the need for earlier detection of recurrence in patients eligible for local salvage treatment. Further studies should focus on comparisons between different salvage local treatment options within high-level evidence trials. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04307056.