Histotripsy is a groundbreaking non-invasive technique for treating primary and secondary liver cancers that utilises high-intensity ultrasound to destroy tumours by mechanical force. Histotripsy is used for liver cancers that are hard to remove with surgery or do not respond to chemotherapy, radiation, and ablation (heating or freezing). The histotripsy procedure – carried out as an outpatient – is quick, effective, and largely painless with few side effects. This aids recovery, reduces disease progression, and improves survival. Research is ongoing to determine if other cancers (including kidney and pancreas) can be successfully treated with histotripsy.
Incidence of liver cancer and current treatments
Harmful levels of alcohol consumption, rising obesity rates and the spread of hepatitis infections have fuelled a 40% rise in liver cancer cases in the UK over the past decade. There are currently around 6000 deaths a year due to liver cancers, and the numbers keep rising. Liver cancer has one of the lowest survival rates of all cancers with only 13% of patients living for five years or longer following an initial diagnosis.
Liver cancers are hard to treat. They are frequently the result of primary breast, bowel, and lung cancers that spread to the liver. Current treatments for liver cancer including chemotherapy, radiation, and surgery requiring incisions often have unpleasant side effects. Ablation, involving heating or freezing the tumour is an established approach used for small cancers, but it has side effects and limitations. These traditional treatments frequently cause physical and emotional pain further limiting the dosages that can be used. Not all patients are suitable for these procedures, either because the tumours have developed resistance, or because the tumours lie close to critical structures such as the bile duct and blood vessels.
Advantages of histotripsy
Clearly, novel approaches to treating liver cancer are needed. Histotripsy is one such approach (In Greek, histotripsy means ‘crushing tissue’). It involves a process called cavitation whereby high-frequency focused ultrasound precisely targets the tumour tissue by creating minute bubbles that form in microseconds and degrade rapidly, tearing the tumour cells apart. The precision of the technique ensures that surrounding tissues are hardly affected. Unlike thermal ablation, the tumour treated with histotripsy does not heat up and cause damage to adjacent non-cancerous tissues. Moreover, since histotripsy does not require a surgical incision, there are fewer risks such as pain, bleeding, scarring and infection, and the patient recovers in a shorter time.
Although anaesthesia is normally required, the whole procedure can be carried out in 60 minutes or less, and the patient can usually go home the same day. This frees up beds and surgeons’ time to deal with more complex cases. Histotripsy was approved in the USA for benign, hepatocellular, and metastatic liver cancers in October 2023, and received the go ahead in 2025 for use in the NHS. Although the data are incomplete, early trials have indicated that the success rate for histotripsy is an acceptable 95% for 44 lesions, with a low level of serious complications of less than 7%.
Future directions and challenges
The histotripsy procedure is effective and is rapidly completed with few side effects. Because the treated tumour debris must be cleared by the immune system, histotripsy is still potentially vulnerable to the same types of risk of side effects as ablation. Is a single histotripsy treatment sufficient to cure diverse types of liver cancer including cancers that have spread to the liver from other locations? Might the tumour return later at the same or a different site? These questions emphasise the importance of long-term patient monitoring.
Not all liver cancers are suitable for histotripsy, either because there are too many lesions or the tumour lies close to critical bodily structures. It is unlikely that histotripsy will replace conventional procedures, but it promises to become an important weapon in the anti-cancer armoury. Each histotripsy procedure costs at least US$12.5k which limits its widespread use. Nevertheless, around 1500 patients, mainly in the USA, have undergone the procedure.
Preliminary studies suggest that histotripsy may stimulate the patient’s own immune system resulting in killer T-cells migrating to the site of the procedure and to the sites of other cancers if present. It remains to be determined whether this unexpected and potentially useful immune response contributes to the destruction of liver tumours.
In conclusion, histotripsy is showing considerable promise as an effective non-invasive procedure for treating primary, benign, and metastatic liver cancers. Several other types of important cancers are being investigated for their vulnerability to histotripsy, including hard-to-reach cancers of the kidney and pancreas. Histotripsy technology is constantly evolving, which is why health professionals are optimistic that many types of cancer will be treatable with histotripsy in the not-too-distant future. For the many thousands of families facing liver cancer, histotripsy could be truly life-saving.
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