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The interventional procedures advisory committee considered evidence on melphalan chemosaturation with percutaneous hepatic artery perfusion and hepatic vein isolation for primary or metastatic cancer in the liver from several sources. This included evidence submitted by 1 company, a review of efficacy and safety evidence and responses from stakeholders. Full details are available in the project documents for this guidance.
The most common types of primary liver cancer are hepatocellular carcinoma (also known as hepatoma) and cholangiocarcinoma. However, cancer in the liver has often metastasised from other sites, such as the lung, colon, stomach and eye (particularly ocular melanoma).
In the UK, around 750 people are diagnosed with ocular melanoma each year. The most common type is uveal melanoma. About half of people with uveal melanoma will develop metastases, most often in the liver. The median overall survival from developing distant metastatic disease varies from about 2 to 12 months.
Treatment for primary or metastatic cancer in the liver depends on several factors, including the location and stage of the cancer, how much liver function is preserved and any relevant comorbidities. Treatment options include surgical resection, thermal ablation, systemic drug therapies, transarterial (chemo)embolisation, isolated hepatic perfusion, external beam radiotherapy and selective internal radiation therapy. In people with primary liver cancer, surgical removal with curative intent and liver transplant may be possible. For most people with liver metastases, treatment with curative intent is not possible.
There are few treatment options for people with ocular melanoma liver metastases. Chemotherapy is generally not used. In the UK, immunotherapy (tebentafusp) is an option for people who test positive for the HLA-A*02:01 allele, which is around half of the uveal melanoma population.
Different treatment options are available for primary or metastatic cancer in the liver. Systemic chemotherapy is given at a low dose to minimise damage to healthy organs. This low dose may mean undetected microtumours may not be treated. A localised higher dose of melphalan chemotherapy could treat these undetected microtumours, as well as visible tumours.
There is a particular unmet need for people with metastases in the liver from ocular melanoma, of which uveal melanoma is the most common type. Metastatic uveal melanoma is associated with poor survival and there is a lack of effective treatment options. NICE's technology appraisal guidance on tebentafusp recommends tebentafusp for treating HLA-A*02:01-positive unresectable or metastatic uveal melanoma in adults, which is around half of the uveal melanoma population. This means there are no effective treatment options for about half of the people who have advanced uveal melanoma. This can create a significant psychological burden for patients and their families, who may feel distress and uncertainty in the absence of viable treatments. Also, tebentafusp is not curative and some people may have tumours that do not respond to it. Melphalan chemosaturation with percutaneous hepatic artery perfusion and hepatic vein isolation is suitable for people with or without the HLA-A*02:01 genotype.
The procedure's targeted approach minimises systemic exposure to the chemotherapy drug. Because the hepatic vein is isolated, a much higher concentration of the chemotherapy drug can be administered than in systemic chemotherapy. By delivering the drug to the entire liver, it can potentially treat undetected microtumours in the liver as well as visible tumours, unlike targeted ablation or embolisation procedures. The technique allows treatment of the entire liver in a single session. This is important for people with metastatic uveal melanoma for whom other liver-directed treatment options may be unsuitable because often they have multiple small-volume tumours in their liver.
NICE did a rapid review of the literature on the efficacy and safety of this procedure. The prioritised evidence included 1 randomised controlled trial, 1 pooled analysis from the randomised controlled trial and a non-randomised phase of the same study, 1 pooled analysis of multicentre case series, 1 retrospective non-randomised comparative study, 3 prospective single-arm studies and 7 retrospective case series. The evidence informing this guidance was only in 1 device. It is presented in the summary of key evidence section in the interventional procedures assessment report. Other relevant literature is in the appendix of the assessment report.
The professional experts and the committee considered the key efficacy outcomes to be:
overall survival
progression‑free survival
tumour response
quality of life.
The professional experts and the committee considered the key safety outcomes to be:
procedure-related complications (including vascular injury, bleeding, thrombosis and cardiovascular events)
bone marrow or haematological toxicity
death.
19 commentaries from people who have had this procedure were discussed by the committee. Survey respondents cited an improvement in quality of life and extended survival after having the procedure. A patient organisation submission highlighted the physical, emotional and psychological burden on people with the condition and their carers.
Patient selection and timely access to treatment is important because people who are physiologically fitter and have less extensive cancer in the liver can have better outcomes.
This procedure addresses only cancer in the liver. People might have metastatic disease in other areas of the body.
The procedure is highly complex with a steep learning curve, so it should only be done in specialist centres with access to a multiple disciplinary team trained in this procedure. The committee was informed that there are fewer intraprocedural adverse events when the procedure is done in specialist centres with more experience.
Although the reported rate of adverse events is high, most chemotherapy-related events are transient and some may be asymptomatic.
People with lived experience stated that this procedure allows them to maintain quality of life as they can quickly return to usual activities.
Collection of data as part of a randomised controlled trial may be limited by people being unwilling to receive best alternative care. But, the committee acknowledged that data can be collected through registries or by using indirect comparisons or historical control data to address some evidence gaps.
The evidence to be generated should include analysis of response rate stratified by the number of treatment cycles, and subgroup analyses to better understand which patient groups are most likely to benefit from the procedure. There should be adequate matching for confounders between treatment and control groups.
The evidence considered by the committee only included adults.
The incidence rates for eye cancer in the UK are highest in people aged 75 to 79. The committee was informed that a notable proportion of people diagnosed with uveal melanoma are younger than 60.
The procedure is only offered in a small number of specialist centres in the UK. This may create challenges in accessibility and geographic equity. Delays in diagnosis and treatment may also further widen disparities in care.
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