Current Status of Histotripsy: Liver, Renal, and Beyond

At the Symposium on Clinical Interventional Oncology (CIO), held in Miami, Florida on October 18, 2025, Mishal Mendiratta-Lala, MD, of the University of Michigan presented an in-depth review of the current clinical status of histotripsy for the liver and emerging nonhepatic applications.¹ The session emphasized that while histotripsy offers a nonthermal, tissue-selective ablation option, its role in routine oncologic care is still evolving and must be guided by evidence and multidisciplinary consensus.

Histotripsy is a noninvasive ultrasound-based ablation technique that uses high-amplitude, microsecond ultrasound pulses to generate cavitation bubble clouds within tissue, resulting in mechanical cellular destruction and leaving a liquid, acellular debris. Unlike thermal ablation, histotripsy avoids heat-sink effects and spares critical vascular and biliary structures.

Dr Mendiratta-Lala summarized existing clinical evidence, including 5 published studies and several case reports, with the most robust data coming from liver applications. The HOPE4LIVER single-arm pivotal trial, which evaluated the HistoSonics system, reported approximately 90% local control at 1 year.² In a real-world safety data study of 230 patients treated across 9 centers, major complications (Clavien-Dindo grade V) were seen only in patients with advanced disease; all complications (n = 3 [1.3%]) were death due to disease progression.³

The session highlighted the potential advantages of histotripsy for treating centrally located liver tumors, where microwave ablation or stereotactic body radiation therapy may carry higher risks of complications, including bile-duct injuries and incomplete ablation due to the heat-sink effect. Through its tissue-selective mechanism, histotripsy circumvents these risks.

Despite this procedural benefit over thermal strategies, operators must weigh the reported outcomes when opting for histotripsy. In a cohort of 31 patients, local recurrence-free survival at 1 year ranged from 35% to 40%, with most recurrences occurring within 6 months, underscoring the need for close follow-up.¹

Beyond the liver, Dr Mendiratta-Lala reviewed applications of histotripsy in renal tumors, including the CAIN Feasibility Trial⁴ and preclinical studies in animal models,⁵ as well as in the pancreas^5,6 and for intracerebral hemorrhage.⁷ Of note, these indications remain investigational and, in some cases, not FDA approved.

According to Dr. Mendiratta-Lala, histotripsy should currently be viewed as “another tool in our toolbox,” rather than a replacement for established standards of care.¹ She emphasized that immunomodulation and abscopal effects remain unproven and cautioned against treating patients outside multidisciplinary liver tumor board (MDLTB) recommendations based on patient demand.

Ethical and clinical dilemmas were illustrated through case examples in which patients opted for histotripsy despite consensus recommendations for resection or intra-arterial therapies. These cases highlighted the tension between patient autonomy and evidence-based practice, particularly given the lack of data on expected treatment response and pathologic confirmation. One example was a case of a man who was recommended resection and HAIP pump by the MDLTB but insisted on histotripsy. While the first 6 months post-histotripsy demonstrated positive progress, at 1-year his ctDNA was rising, and disease was again present in several of the treated areas.¹ Another case exemplified a rare complication of histotripsy: pseudoaneurysm. Although conservative management was recommended, the patient elected to undergo histotripsy. A pseudoaneurysm subsequently developed within the treatment cavity, resulting in severe hemorrhage and hemorrhagic shock. This case underscores the importance of meticulous review of immediate post-treatment imaging for prompt identification of complications.¹

For clinicians, the session reinforced that histotripsy may offer a nonthermal, bile duct-sparing option for selected liver tumors, particularly centrally located lesions, when applied within a structured, multidisciplinary workflow. However, limited publications—all of which report on small study populations and lack homogeneity—operator variability, and uncertain long-term outcomes mean that careful patient selection, rigorous imaging follow-up, and participation in registries or trials are essential before broader adoption.

Histotripsy represents a promising, FDA-approved nonthermal ablation modality for liver tumors, with encouraging early safety and efficacy signals. Nevertheless, its definitive role in interventional oncology awaits larger prospective registries and clinical trials to guide evidence-based integration into clinical practice.

1. Mendiratta-Lala M. Current status of histotripsy: liver, renal, and beyond. Presented at: Symposium on Clinical Interventional Oncology (CIO); October 17-19, 2025; Miami, FL.
2. Ziemlewicz TJ, Critchfield JJ, Mendiratta-Lala M, et al. The #HOPE4LIVER single-arm pivotal trial for histotripsy of primary and metastatic liver tumors: one-year update of clinical outcomes. Ann Surg. 2025;282(6):908-916. doi:10.1097/SLA.0000000000006720
3. Wehrle CJ, Burns K, Ong E, et al. The first international experience with histotripsy: a safety analysis of 230 cases. J Gastrointest Surg. 2025;29(4):102000. doi:10.1016/j.gassur.2025.102000
4. Wah TM, Amaral JF, Laeseke PF. Treatment of primary solid renal tumours using histotripsy: study protocol for the CAIN feasibility trial. Cardiovasc Intervent Radiol. 2025;48(6):857-865. doi:10.1007/s00270-025-04035-5
5. Falk KL, Laeseke PF, Kisting MA, et al. Clinical translation of abdominal histotripsy: a review of preclinical studies in large animal models. Int J Hyperthermia. 2023;40(1):2272065. doi:10.1080/02656736.2023.2272065
6. Gannon J, Imran KM, Hendricks-Wenger A, et al. Ultrasound-guided noninvasive pancreas ablation using histotripsy: feasibility study in an in vivo porcine model. Int J Hyperthermia. 2023;40(1):2247187. doi:10.1080/02656736.2023.2247187
7. Gerhardson T, Sukovich JR, Chaudhary N, et al. Histotripsy clot liquefaction in a porcine intracerebral hemorrhage model. Neurosurgery. 2020;86(3):429-436. doi:10.1093/neuros/nyz089