Histotripsy, a novel noninvasive ultrasound therapy, shows promise in the treatment of liver and biliary tract cancers. At the 2025 Cholangiocarcinoma (CCA) Summit, experts engaged in a crossfire debate examining histotripsy’s capabilities, limitations, and the evidence required to support its application in CCA. The session featured Kevin Burns, MD, advocating for the potential of histotripsy, and Brock Hewitt, MD, MPH, presenting the opposing argument.
Dr Burns first outlined the advantages of histotripsy, highlighting its unique mechanism of action, which uses high-amplitude, high-pressure ultrasound waves to achieve immediate tissue destruction, unlike microwave- or radiation-based techniques, when the reduction in tumor size is often delayed. He emphasized histotripsy’s precision in treating tumors in complex anatomical locations, in addition to preserving critical structures such as blood vessels, ducts, arteries, and veins >2 mm. To support his argument, Dr Burns cited the prospective, multicenter Hope4Liver study, which evaluated histotripsy for treating primary and metastatic liver tumors. The study reported 95.5% technical success, 90.0% local tumor control at 1 year, and had low rates (6.8%) of major complications.1 Additionally, real-world data from 230 patients across multiple cancer types revealed approximately 95.0% of patients had no complications within 30 days.1 These findings underscore histotripsy’s strong safety profile and growing clinical relevance, reflected in its inclusion in the United Network for Organ Sharing guidelines as a locoregional therapy option for liver transplant candidates with primary liver tumors.
Dr Burns further illustrated the clinical impact of histotripsy through case studies, including a patient with metastatic CCA who, after receiving histotripsy, experienced tumor involution, improved tumor marker profiles, and an enhanced quality of life, enabling the patient to achieve personal life goals during their remaining time. He concluded that histotripsy could address clinical gaps in managing central lesions and biliary obstructions, and may have a place as a therapeutic option for CCA.
Dr Hewitt presented the opposing perspective, advocating for cautious optimism regarding histotripsy. Although he acknowledged the encouraging safety data, he highlighted several limitations, including challenges with tumor visibility and accessibility, particularly for lesions obscured by ribs situated near gas-filled organs, or located deep within the body.2 Additionally, larger tumors often necessitate overlapping treatments, which introduces procedural complexity.
Dr Hewitt also pointed out the lack of robust histological evidence from human studies, raising concerns about incomplete tumor destruction, particularly in stromal tissues, as seen in preclinical models. He stressed that although histotripsy offers significant promise, its curative potential and long-term efficacy remain unproven. To address these uncertainties, he called for rigorous clinical trials, and establishment of standardized patient selection criteria to ensure appropriate use and avoid the risk of overextension.
The discussion then expanded to explore future directions for histotripsy, with a focus on careful patient selection, and the need to distinguish between palliative and curative intent. Experts emphasized the importance of conducting randomized controlled trials to compare histotripsy with the established standard of care. They also highlighted practical considerations, such as standardized training protocols, as well as software and hardware enhancements to improve treatment precision and reproducibility. Finally, the session underscored the importance of a collaborative, data-driven approach to advancing histotripsy. Although histotripsy holds significant potential, the experts agreed that patient safety must remain the priority, and further research is essential to define its role within the broader landscape of cancer therapy.
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