Histotripsy: A Noninvasive Path for Treating Liver Tumors

The Froedtert & MCW Cancer Network offers an innovative treatment alternative for liver tumors. Traditionally, surgery has been the standard of care, but minimally invasive procedures are playing an increasing role — including ablation, which destroys tumor tissue and embolization, which blocks blood flow to tumors.

Histotripsy is ablation technology that uses focused ultrasound to break down tumors. Instead of cutting, burning or radiating tumors, histotripsy uses the power of sound waves to mechanically break down tumor tissue.

The Cancer Network was one of 14 sites worldwide that participated in the #HOPE4LIVER clinical trial, which led the FDA to approve the technology for liver tumors. The Cancer Network began offering histotripsy to select patients in fall 2025.

How Histotripsy Works

Histotripsy is not surgery and it is not radiation. It is a form of focused ultrasound, but it works differently than the diagnostic ultrasound scans used to look at babies during pregnancy. It is different from the ablation techniques used in the last 15 to 20 years, which are generally heat- or cold-based therapies. Histotripsy is nonthermal and noninvasive, meaning we don’t have to put a probe or device into the patient to destroy the tumor.

The mechanism of action uses ultrasound energy to create tiny bubbles or cavities that collapse and destroy targeted tissue without damaging nearby structures. These bubbles form a "bubble cloud." The rapid expansion and collapse of these micro-bubbles create a mechanical force strong enough to liquefy the targeted tissue. The process destroys the tumor cells completely, turning them into a liquid debris that the body can naturally absorb and flush out over time.

Non-Thermal and Non-Ionizing

“Non-thermal" and "non-ionizing" are important distinctions that separate this treatment from other options. 

• Non-thermal: Most ablation techniques (like radiofrequency ablation or microwave ablation) work by heating the tumor to incredibly high temperatures to kill the cells. While effective, heat can sometimes damage nearby blood vessels, bile ducts or healthy organs. Because heat spreads, specialists are very careful near delicate structures. Histotripsy does not use heat. It uses mechanical force, making it safer to use near critical structures in the liver because there is no "heat sink" effect where blood flow cools the treatment area and there is no risk of accidental burns to surrounding tissue.
• Non-ionizing: Radiation therapy uses ionizing energy to damage the DNA of cancer cells. While powerful, radiation has lifetime limits and can cause side effects like fatigue or skin irritation. Histotripsy uses sound waves, which are non-ionizing. This means it carries no radiation risks and importantly, the procedure can be repeated if new tumors appear later.

Who Is a Candidate for Histotripsy

Determining if you are eligible for histotripsy involves a detailed evaluation by a multidisciplinary team, usually including interventional radiologists, surgical oncologists and hepatologists.

Histotripsy has been approved for people with tumors that start in the liver, as well as tumors that metastasize (spread) to the liver from other cancer sites in the body. However, it will not be standard treatment for every person with liver cancer. Individual factors, including the number of tumors, their size and location, may make a different therapy a better choice.

Histotripsy could also eventually be used to treat cancer in other organs beside liver. Researchers are conducting a clinical trial on its use in kidney cancer and there is preclinical work being done in pancreatic and prostate cancers with plans for clinical trials in those disease sites. Our multidisciplinary group has been considering participation in these trials, as well as research we’d like to put forward. A lot of work still needs to be done to determine which patients will benefit most from histotripsy.

Treatable Conditions

Currently, histotripsy is primarily focused on the liver. It is used to treat two main categories of liver tumors:

1. Primary liver cancer: This refers to cancer that started in the liver, most commonly Hepatocellular Carcinoma (HCC). 
2. Metastatic liver tumors: This refers to cancer that started elsewhere in the body (like the colon, breast or pancreas) and has spread (metastasized) to the liver.

Key Factors for Eligibility

Your medical team will look at several specific factors to decide if this is the right path for you:

• Tumor size: While the technology can treat various sizes, large tumors may require longer treatment times or multiple sessions. Generally, tumors under a certain diameter (less than 5 centimeters) are ideal.
• Tumor location: The tumor must be visible via ultrasound imaging. Since the doctor uses real-time ultrasound to guide the robot, they must be able to see the target clearly. If a tumor is hidden behind the lungs or ribs in a way that blocks the sound waves, it might be difficult to treat.
• Liver function: Your liver must be healthy enough to handle the procedure. Doctors measure this using blood tests and scoring systems (like the Child-Pugh score) to ensure your liver can recover and process the waste from the destroyed tumor.
• General health: Although it is less invasive than surgery, it still requires general anesthesia. Candidates must be healthy enough to undergo anesthesia safely.

Who Might Not Be Eligible

There are certain situations where histotripsy might not be recommended:

• Patients with active infections.
• Patients with uncorrectable bleeding disorders.
• Patients with tumors located in areas that cannot be targeted safely without passing through hollow organs (like the stomach or bowel), as the air in these organs blocks sound waves.
• Patients who have implanted cardiac devices or other metal implants in the direct path of the sound beam.

Why Histotripsy Is an Important Development for Liver Cancer Treatment

There have been significant limitations in current treatments for tumors in some areas of the body. Tumors that are close to critical structures are challenging from surgical, interventional radiology and radiation oncology perspectives. This includes liver tumors near the major bile ducts or next to the gallbladder or tumors close to the liver capsule near other organs. Histotripsy has the potential to make an impact on what have previously been “no fly zones” in the liver, allowing us to treat more patients in these situations.

Benefits of Histotripsy Treatment

Histotripsy offers a unique set of benefits that appeal to both patients and physicians.

• Precision: The robotic system allows for sub-millimeter accuracy. Doctors can plan the treatment zone meticulously and verify in real-time that the tissue is being destroyed.
• Preservation of healthy structures: The mechanical nature of histotripsy is "tissue selective." While it destroys liver cells and tumor cells easily, structures rich in collagen — like large blood vessels and bile ducts — are more resistant to the sound waves. This means a tumor sitting right next to a major vein can often be treated safely without rupturing the vein.
• No incisions or needles: This reduces the risk of infection at the entry site, eliminates the need for wound care.
• No implant restrictions: Unlike MRI-guided treatments that restrict patients with metal implants, histotripsy uses ultrasound guidance, which is generally compatible with most metal implants (as long as they aren't blocking the sound path).
• Immunological potential: This is an exciting area of ongoing research. Early studies suggest that mechanically destroying the tumor (rather than burning it) releases tumor antigens in a way that might stimulate the body's immune system to recognize and fight cancer cells elsewhere in the body.

Risks and Side Effects

No medical procedure is without risk. While histotripsy is non-invasive, it involves potent energy delivered to a vital organ. It is important to have a transparent discussion with your doctor about potential complications.

Common Side Effects

Most patients experience relatively mild side effects that resolve within a few days:

• Abdominal pain: Mild soreness or discomfort in the upper right abdomen where the treatment occurred.
• Fatigue: Feeling tired for a few days after the procedure is common as the body recovers from anesthesia and begins to reabsorb the treated tissue.
• Nausea: Some patients may feel nauseous due to the anesthesia or the body's reaction to the tissue breakdown.

Potential Risks and Complications

Although rare, more serious complications can occur:

• Skin burns: Even though the technology is non-thermal, if the coupling (water connection) isn't perfect, there is a very small risk of skin irritation or burn at the surface, though the system has safeguards to prevent this.
• Bleeding: While major vessels are usually spared, there is a risk of bleeding within the liver capsule.
• Infection: Anytime tissue is destroyed inside the body, there is a small risk that the liquefied area could become infected (abscess), requiring antibiotics or drainage.
• Targeting errors: There is a risk of the sound waves affecting tissue outside the target zone, such as the rib cage (causing pain) or nearby organs, though the robotic precision minimizes this.