Histotripsy was cleared by the U.S. Food and Drug Administration in 2023 for the treatment of primary and metastatic liver tumors. In a research letter published in JAMA Network Open, Sears et al reported findings from a retrospective cohort study evaluating national practice patterns and short-term outcomes as adoption of the procedure expanded, with implications for patient selection.
“In this national cohort, histotripsy was widely adopted and was most commonly performed in the outpatient setting, with low rates of laboratory toxic effects and procedural complications,” the investigators commented. “However, several practice patterns merit attention.”
Study Details
Using the Epic Cosmos database, the investigators identified 972 adult patients (median age = 67.0 years; 51.4% male) who underwent histotripsy between 2023 and 2026. Data on demographics, geographic distribution, indications, comorbidities, and liver function before and after the procedure were extracted.
Laboratory outcomes were assessed according to Common Terminology Criteria for Adverse Events (CTCAE) grading for aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, and total bilirubin. Acute kidney injury was defined using the Kidney Disease: Improving Global Outcomes (KDIGO) serum creatinine criteria. The analyses of 30-day outcomes considered length of stay, emergency department visits, readmission, and mortality.
The investigators performed descriptive analyses.
National Practice Patterns
Most patients were treated in urban centers (88.2%). Nearly half of the cohort had commercial insurance (47.3%), while 32.3% were covered by Medicare and 4.5% were self-paying or uninsured.
Histotripsy was performed for metastatic disease to the liver in 69.8% of patients and for primary malignant liver tumors in 30.2%. Among metastatic tumors, colorectal cancer (26.7%) and pancreatic cancer (12.4%) were the most common primary sites. Hepatocellular carcinoma (22.0%) and intrahepatic cholangiocarcinoma (8.2%) were the most common histologic types among primary liver tumors.
These findings “[raise] concern that histotripsy is being used in patients with disease biology poorly suited to liver-directed therapy,” the investigators wrote.
Liver function at baseline appeared to vary across the cohort. The median score on the Model for End-Stage Liver Disease (MELD) was 9.7. Among the 675 patients for whom preprocedural Albumin-Bilirubin (ALBI) scores could be calculated, 35.6% were grade 1, 43.2% were grade 2, and 21.2% were grade 3.
Short-Term Outcomes
Histotripsy was predominantly performed in the outpatient setting, and 87.6% of patients underwent a single treatment session. Most patients were discharged on the same (88.4%) or following (92.3%) day, while 2.9% remained hospitalized for at least 4 days.
Laboratory toxicities were uncommon, according to the investigators, with most patients demonstrating CTCAE grade 0 to 1 elevations in AST, ALT, alkaline phosphatase, and bilirubin after treatment. Acute kidney injury was documented in 1.2% of patients.
Although procedural toxicity was described as low, the 30-day mortality rate was 11.1% and was overall similar across payer groups. The investigators wrote that this mortality rate “is difficult to reconcile with a procedure intended for local disease control.” Readmission and emergency department visit rates were 0.9% and 0.4%, respectively.
“These findings suggest a mismatch between histotripsy’s technical safety and the clinical context in which it is applied,” the investigators remarked.
They concluded, “These results provide an early national snapshot of histotripsy use and highlight the need for clearer patient selection criteria as adoption expands. Prospective outcomes studies will be essential to define the appropriate role of histotripsy in the treatment of primary and metastatic liver tumors.”
Multidisciplinary evaluation involving surgical oncology, medical oncology, interventional radiology, and hepatology may help refine patient selection as prospective evidence develops.
Allan Tsung, MD, of the University of Virginia, Charlottesville, is the corresponding author of the article in JAMA Network Open.
Disclosure: For full disclosures of the study authors, visit jamanetwork.com.
