Salvage HIFU demonstrates encouraging mid-term outcomes in radiorecurrent prostate cancer

Data from the HIFI-2 study (NCT04307056) have been published in European Urology Oncology, showing that salvage high-intensity focused ultrasound (HIFU) for localized prostate cancer recurrence after radiotherapy may offer promising oncologic control while preserving quality of life.¹

The findings, taken from a large, prospective trial, address a persistent clinical gap in the management of radiorecurrent prostate cancer, where curative-intent options remain limited and often associated with substantial morbidity.

“This large prospective multicenter study demonstrates that salvage HIFU can achieve clinically meaningful oncologic control while maintaining an acceptable safety profile in patients with localized recurrence after radiotherapy,” said lead author Guillaume Ploussard, MD, PhD, in a news release on the results.² “In a setting where treatment options offering curative intent remain elusive and often come with significant morbidity, these results are particularly meaningful. Combined with the growing body of clinical evidence, this study further supports HIFU’s transition toward becoming a standard of care for appropriately selected patients.”

Trial overview

The HIFI-2 study was a prospective, nationwide trial conducted across 32 centers in France between 2015 and 2019. A total of 531 patients with biopsy-confirmed, intraprostatic recurrence following primary radiotherapy and no evidence of metastatic disease were enrolled. The primary end point was androgen deprivation therapy–free survival (ADT-FS), with secondary end points including prostate cancer–specific survival, overall survival, and functional outcomes.

The median age of patients was 75 years, and the median prostate-specific antigen (PSA) level was 4.5 ng/mL at the time of salvage HIFU. Post-treatment PSA levels declined to a median of 0.7 ng/mL at 12 months and 1.02 ng/mL at 30 months. The overall 30-month ADT-FS rate was 71% (95% CI, 67 to 76).

Outcomes were more favorable among patients with lower disease burden at baseline. Those with pre-HIFU PSA levels of 4.5 ng/mL or lower and Gleason scores of 6 to 7 achieved ADT-FS rates of up to 84% at 30 months (95% CI, 78 to 91).

Regarding safety, high-grade complications (Clavien-Dindo >IIIa) were reported in 19 of 531 patients. International Prostate Symptom Scores increased from a median of 6.0 at baseline to 10.1 at 6 months and remained unchanged up to 30 months. Stress urinary incontinence did not change significantly over time (P = .6). Severe urinary incontinence increased from 7% at baseline to 12% following treatment.

However, patient-reported quality of life, assessed using the EORTC QLQ-C30 instrument, did not show significant deterioration at 12 months.

Interpretation and limitations

The authors acknowledged several limitations, including the mid-term follow-up and evolving guideline recommendations surrounding post-S-HIFU recurrence during the study period. They emphasized that longer-term follow-up beyond the primary end point time is awaited, and that further studies are needed to compare different salvage local options.

Overall, they concluded that this prospective study supports the mid-term oncologic safety and tolerability of salvage HIFU in patients with radiorecurrent prostate cancer. They also underscored the importance of early detection of recurrence, noting that pre-HIFU PSA was a key predictor of treatment success.

REFERENCES
1. Ploussard G, Coloby P, Chevallier T, et al. Salvage high-intensity focused ultrasound for prostate cancer recurrence after radiotherapy (HIFI-2 study). Eur Urol Oncol. 2026 Apr 28:S2588-9311(26)00112-4. doi:10.1016/j.euo.2026.04.007

2. EDAP TMS strengthens market position with landmark HIFI-2 data supporting Focal One® Robotic HIFU in radiorecurrent prostate cancer. News release. EDAP TMS S. A. April 30, 2026. Accessed April 30, 2026. https://www.globenewswire.com/news-release/2026/04/30/3284855/9622/en/edap-tms-strengthens-market-position-with-landmark-hifi-2-data-supporting-focal-one-robotic-hifu-in-radiorecurrent-prostate-cancer.html