Histotripsy for renal cell carcinoma: from animal studies to clinical application.

Histotripsy is a novel non-thermal, noninvasive, non-ionising ablation modality that is under investigation for the treatment of renal cell carcinoma (RCC). Histotripsy utilizes a focused ultrasound transducer that creates high peak negative pressures at a focal point to cause cavitation in tissue. The rapid expansion and collapse of endogenous gas bubbles mechanically destroy targeted tissue while sparing collagen-containing critical structures such as the renal pelvis and ureter. This review aims to prepare physicians for the clinical translation of cavitation histotripsy for the treatment of RCC by introducing the basic principles, tissue effects, and results of ex vivo and live animal studies.

This review synthesizes the current literature on cavitation histotripsy for RCC. Special emphasis is placed on the differences between histotripsy and current minimally invasive ablative modalities, the potential of histotripsy for managing kidney tumors, a comprehensive review of preclinical studies, and preliminary findings from early human clinical trials.

Preclinical studies have demonstrated that histotripsy can effectively ablate target tissue while sparing nearby critical structures. Histotripsy is not limited by heat-sink effects and may have a reduced risk of off-target damage due to its tissue-selective properties.

Histotripsy is currently in clinical trials for use in treating RCC. Ongoing clinical trials, CAIN and HOPE4KIDNEY, will provide critical data on the efficacy, potential complications, and limitations of histotripsy for treating RCC.

International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group. 2026 Jul 24 [Epub]

Ali Mutlu, Katrina L Falk, Adrienne L Kisting, Erica M Knavel Koepsel, Martin G Wagner, J Louis Hinshaw, Daniel D Shapiro, E Jason Abel, John F Swietlik, Paul F Laeseke, Timothy J Ziemlewicz, Fred T Lee, Edwarda D Golden

Department of Radiology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.