Key Takeaways

• Histotripsy is a non-invasive ultrasound treatment that can destroy liver tumors without surgery.

• It is FDA-authorized for liver tumors, including liver metastases from breast cancer.

• Most treatments are completed in a single outpatient visit.

• Early studies show promising local tumor control and a favorable safety profile.

• Researchers are investigating whether histotripsy may stimulate the immune system to attack cancer elsewhere in the body.

• Histotripsy is not currently approved for treating primary breast tumors, but clinical trials are underway.

Tissue ablation techniques have long been used to treat various forms of cancer. However, many of these techniques are invasive and can cause substantial adverse effects. Histotripsy is the first non-invasive, non-ionizing, and non-thermal ablation technology to be introduced.

Histotripsy was developed over more than two decades of research at the University of Michigan, but it only became commercially available following FDA authorization in 2023. That authorization was for the non-invasive destruction of liver tumors, including metastatic tumors that have spread to the liver. This means that some patients with stage IV breast cancer and liver metastases may be candidates for treatment.

Johns Hopkins Medicine was one of the first US centers to use histotripsy. At Johns Hopkins Medicine they state “candidates for histotripsy are typically patients for whom traditional surgical methods, chemotherapy or radiation pose unacceptably increased risks or have been ineffective.”

How Does Histotripsy Work?

First of all, the name. In Greek, ‘Histo’ means ‘soft tissue’, and ‘tripsy’ refers to breakdown.

A patient’s doctor will let them know if they are good candidates for histotripsy. After planning the therapy by sonography, a robotic arm performs the ablation point by point in a marked tumor area with an appropriate safety zone. It is guided by real-time ultrasound imaging and uses short ultrasound bursts (microseconds in length), and higher peak pressure amplitudes to generate acoustic cavitation from gas within the tissues. Acoustic cavitation is the 1generation, oscillation, and collapse of microbubbles activated by the ultrasound waves. [1]

To put it a bit more plainly, histotripsy works by delivering high-intensity focused ultrasound waves directly at a targeted tumor. These waves create cavitation bubbles within tissues that rapidly expand and collapse, thereby mechanically fractionating the tumor tissue into debris that is subsequently absorbed by the body’s immune system and cleared over subsequent weeks. [2]

Histotripsy of liver tumors is generally performed under general anesthesia with controlled ventilation so that breathing-related movement of the liver can be minimized, allowing the ultrasound beam to remain precisely focused on the target area.

I listened to an interview on a podcast [3] at breastcancer.org featuring Dr Brock Hewitt, a surgeon who uses histotripsy in his medical practice. Dr Hewitt has also authored a number of studies on the procedure.

Dr Hewitt carefully explained that he uses histotripsy for liver metastases, treating only one area at a time, but stating that if there are many lesions in that area, the procedure can treat up to 5-6 lesions at a time. His two main criteria for deciding whether the procedure should be utilized are: Can it improve the quantity of someone’s life? And can it improve the quality of someone’s life?

Key Facts About Histotripsy

• Each treatment only takes about 20 minutes, although expect the entire procedure to take around 90 minutes – 2 hours
• It is considered a low risk procedure
• Depending on the patient’s circumstances, additional histotripsy treatments may be possible if new liver lesions develop or if further treatment is required
• No interruption to systemic therapy: patients generally do not need to pause their chemotherapy, immunotherapy, or targeted drug regimens to undergo histotripsy
• Histotripsy can target lesions near critical blood vessels or bile ducts, destroying the tumor while leaving major vascular structures intact
• The procedure is performed under general anesthesia, and patients are typically able to return home the same day
• It may be suitable for patients for whom traditional surgery or ablation is considered too risky or unsuitable

Histotripsy, the Immune System, and the “Abscopal Effect”

One of the most exciting aspects of histotripsy being studied in breast cancer models is its ability to trigger an immune response. Because histotripsy breaks down cells mechanically rather than burning them, it keeps vital tumor-associated proteins intact. Recent studies demonstrate that histotripsy releases high amounts of intact tumor antigens, such as HER2 proteins, directly into the space between cells (the extracellular space). Researchers believe histotripsy may stimulate the immune system by releasing intact tumor antigens that can be recognized by immune cells. In animal models, this has been associated with shrinkage of untreated tumors elsewhere in the body, a phenomenon known as the “abscopal effect”. Whether this effect can be reliably achieved in humans remains an active area of research.

An animal study published in 2025 [4] had very interesting findings for HER2+ cancers. The researchers hypothesized that the abscopal effect is caused by the activation of the immune system against cancer-related proteins that are released from tumor cells by the sonic disruption. They tested this using a mouse model of breast cancer where one tumor was disrupted with histotripsy. They found that tumors treated this way released a protein called HER2, a well-known tumor antigen found in some breast cancers. They also found that the higher the dose of histotripsy, the more HER2 was released from tumor cells.

Research is Ongoing for Using Histotripsy on Primary Tumors in the Breast

Using histotripsy directly on tumors in the breast is currently undergoing active study. The Chinese University of Hong Kong is conducting trials to evaluate histotripsy as a non-surgical option for early-stage breast cancer. This could eventually serve as an alternative to a lumpectomy for patients with small, single, low-grade tumors.

In addition, researchers are engineering new ultrasound transducers and machine heads designed specifically for breast imaging, precise stabilization, and targeted ablation. Researchers are developing specialized breast-specific histotripsy systems designed to improve imaging, stabilization, and treatment precision. While progress is encouraging, additional clinical trials will be needed before histotripsy becomes a routine treatment option for primary breast tumors.

My Client’s Experience With Histotripsy

Sara lives in Colorado, and has been on a breast cancer healing journey for a number of years. Here is her experience with histotripsy:

“I found that I had a single liver lesion in September of 2025. I had learned about histotripsy earlier that year and put it in my pocket. I contacted a Histotripsy doctor out of California and moved forward without hesitation. In November of 2025, the week before Thanksgiving, I traveled to a hospital in Eastern Oregon to have the procedure. While it is available in my home state of Colorado, I opted to travel so as to work with the referring physician, Dr Kevin Burns. The procedure itself lasted about 90 minutes. It was actually more painful than I had expected, particularly after seeing several people say they were back at it by the next day.

“I had very tender and bruised feeling ribs for the first 3 weeks or so. I also was a little more tired than usual and had to allow more time for rest.

“One interesting effect is that the procedure kills the tumor and is filtered through the kidneys. Because of the dead cells going through the kidneys, my first urine afterwards was black! I had one minor complication which was some internal bleeding from being intubated. As a result, I was coughing up blood for about a month.

“Before Histotripsy, my Signatera was around 40. After Histotripsy it dropped to 12. Unfortunately, my tumor markers kept rising after that. By the time we ran my next 3 month Signatera, it had jumped to 72. A scan confirmed multiple lesions on my liver only 4 months later. While I don’t believe the procedure itself caused progression, I don’t think it really is fully effective without the abscopal effect. My observations from others is that this is not uncommon to have progression at least once.

“You can go back in for as many treatments as needed around 6 weeks apart as long as the kidneys are functioning properly. I have seen people go in for a second and third treatment and have long term clearance after that. It’s still on the table for me.”

While Sara’s experience with histotripsy has been a little up-and-down, and possibly not as encouraging as she had initially hoped, it is quite possible that future treatments will be more successful for her. She is also dealing with two unusual gene mutations that were only recently discovered which are more than likely contributing to the rise in tumor markers.

Please note: Individual results can vary considerably, and one person’s experience should not be viewed as predictive of outcomes for others.

Safety, Possible Risks and Drawbacks

In a 2025 international safety analysis involving 230 patients, researchers reported a favorable safety profile with low rates of serious complications, providing additional support for the procedure’s use in carefully selected patients. [6]

If you are contemplating histotripsy, your doctor will advise you of any possible risks. After reviewing a number of studies, I discovered there can be a risk of infection, possible episodes of pain which resolve in a few days, blood clots and/or bleeding afterward, but the risks of these are considered to be quite low.

While the benefits of histotripsy are very promising, there are unanswered questions about it. Being such a new therapy, there’s not yet robust long-term data about cancer recurrence after treatment. Early studies have shown approximately 90% local tumor control one year after treatment, meaning the treated tumors remained successfully controlled in the majority of patients. [5]

Currently, solid organs like the liver are the best for histotripsy. Bone can block ultrasound from reaching its intended source, ruling out tumors in bones and locations close to bone. And using histotripsy in gaseous organs, like the lungs, could be dangerous, potentially causing damage to nearby healthy tissues.

Where is Histotripsy Available?

I think it’s important to know that clinical trials and preclinical research on histotripsy is rapidly expanding to evaluate its use for primary breast cancers. In the USA, Medicare/Medicaid covers histotripsy, while private insurance coverage varies. Dr Hewitt stated in the podcast at [1] that he has to argue with a lot of companies but 75-80% of them cover it eventually. In Australia and many other parts of the world, histotripsy is not yet available. Several clinics in Europe offer it. It is available in the UK, the first European country to adopt it, and at last check it was available on the NHS. To check in your region, you can do a search for “histotripsy” and your location name.

References:

[1] 2022: Histotripsy: the first noninvasive, non-ionizing, non-thermal ablation technique based on ultrasound – https://pmc.ncbi.nlm.nih.gov/articles/PMC9404673/
[2] 2024: Advances in Tumor Management: Harnessing the Potential of Histotripsy – https://pmc.ncbi.nlm.nih.gov/articles/PMC11148838/

[3] 2026: Podcast on BreastCancer.org – Histotripsy for Breast Cancer in the Liver – https://www.breastcancer.org/podcast/histotripsy-breast-cancer-liver-metastases

[4] 2025: Ultrasound-Guided Histotripsy Triggers the Release of Tumor-Associated Antigens from Breast Cancers – https://www.mdpi.com/2072-6694/17/2/183
[5] 2024: The #HOPE4LIVER Single-arm Pivotal Trial for Histotripsy of Primary and Metastatic Liver Tumors – One-year Update of Clinical Outcomes – https://journals.lww.com/annalsofsurgery/fulltext/2025/12000/the__hope4liver_single_arm_pivotal_trial_for.5.aspx
[6] 2025: The first international experience with histotripsy: a safety analysis of 230 cases – https://pubmed.ncbi.nlm.nih.gov/39978577/

Additional studies:
2025: Histotripsy: Recent Advances, Clinical Applications, and Future Prospects – https://pmc.ncbi.nlm.nih.gov/articles/PMC12469116/
2025: Histotripsy of Liver Metastases: Short-Term Safety and Imaging Findings – https://pubmed.ncbi.nlm.nih.gov/41016946/
2025: Local Tumor Control of Liver Tumors After Histotripsy: A Preliminary National Multicenter Study – https://pubmed.ncbi.nlm.nih.gov/41401400/
2026: Histotripsy for multifocal breast cancer liver metastases with early complete metabolic response: a case report – https://pmc.ncbi.nlm.nih.gov/articles/PMC13095606/

Articles:
University of Michigan Health – What is Histotripsy – https://www.uofmhealth.org/our-care/specialties-services/histotripsy
2025 Article: Histotripsy, a new non-invasive treatment for cancer tumours – https://www.canceractive.com/article/histotripsy-a%20new%20noninvasive%20treatment%20for%20cancer%20tumours
2025 Article: How ultrasound is ushering a new era of surgery-free cancer treatment – https://www.bbc.com/future/article/20251007-how-ultrasound-is-ushering-a-new-era-of-surgery-free-cancer-treatment