Histotripsy for liver tumours: a systematic review and meta-analysis of current clinical evidence.

Abstract

Background: Histotripsy is a novel, non-invasive, non-ionising, non-thermal method of mechanical tumour disruption that received US FDA approval in October 2023 for the treatment of liver tumours. This study aims to summarise and evaluate the safety and outcomes data following histotripsy of primary and secondary liver tumours.

Methods: This systematic review and meta-analysis followed PRISMA guidelines. Records were identified through review of PubMed, Embase, and Scopus (database inception to December 2025) and manual review. Eligible studies were prospective or retrospective cohort studies and clinical trials published in English between Jan 1, 2015 and Dec 31, 2025 reporting clinical outcomes of histotripsy for liver tumours in three or more patients. Literature reviews, editorials, conference abstracts, animal studies, and case reports of two or fewer patients were excluded. Evaluated outcomes included post-procedural complications, local tumour control (LTC), overall survival, procedural technical success, tumour volume reduction, and off-target effects. Study quality was assessed using the Risk Of Bias In Non-randomised Studies of Interventions (ROBINS-I) tool. Heterogeneity was quantified using the I² statistic and Cochran's Q test. Publication bias was assessed using funnel plot visual inspection and Egger's regression test. Finally, the histotripsy technology was assessed using the IDEAL framework to inform the design of future trials. This work was registered with PROSPERO (CRD420261299804).

Findings: Ten studies (553 patients) met inclusion criteria. No studies exhibited a high risk of bias; seven demonstrated a moderate risk of bias in at least one domain. Using a random-effects model, the pooled technical success rate was 94.1% (95% CI: 90.4%-96.4%; I² = 0%). Four studies reported major complications (grade ≥3), with a pooled event rate of 7.0% (95% CI: 2.0%-21.5%; I² = 76.4%). The pooled event rate for absence of nodular enhancement was 89.3% (95% CI: 48.2%-98.7%; I² = 61.6%). The pooled mean tumour volume reduction was 49.4% (95% CI: 9.0%-89.8%; I² = 99.6%). The pooled off-target tumour effect rate was 10.0% (95% CI: 5.0%-20.0%; I² = 6.6%). No significant publication bias was detected for mortality and safety outcomes; however, formal assessment of publication bias was limited by the small number of studies for these and all outcomes. All radiological control outcomes showed substantial heterogeneity across studies.

Interpretation: Although there is notable heterogeneity across studies, pooled results indicate that histotripsy has high rates of technical feasibility and local control with a favourable side effect profile. Interpretation of these findings is limited by the small number of available studies, variability in outcome definitions and imaging assessment methods, and short follow-up durations. These results underscore the need for larger, prospectively designed studies with standardised reporting frameworks and longer follow-up to more precisely characterise the clinical, radiologic, and quantitative imaging outcomes following histotripsy.

Funding: None.