Neuroendocrine Neoplasms (NENs) present complex challenges to diagnosis and treatment. Even in metastatic cases spreading to the liver, there are some important differences compared to the more common types of gastrointestinal tumours and pancreatic adenocarcinomas, e.g. their sometimes-indolent nature and their ability to oversecrete hormones causing distinct clinical syndromes. Also, the tumours are known to be highly vascular which is a feature where growth inhibition and symptom relief may be achieved by specific ‘blocking’ agents – this is particularly the case with liver metastases in well-differentiated Neuroendocrine Tumours (NETs).

Spread to the liver may occur from NETs of the foregut, midgut as well as hindgut. NET metastases are usually multiple and of varying size. In most cases, both liver lobes are affected, but widespread (miliary) seeding throughout the liver is seen only occasionally according to my research. Midgut NETs are the most type causing liver metastases, especially when of small intestine origin. Appendix NETs unusually give rise to hepatic spread and hindgut, particularly rectal less than 2 cm rarely metastasise to the liver. Many NET patients will have been initially diagnosed via liver biopsy indicating late diagnoses are pretty common. Pancreatic NETs vary in malignant potential and frequency of liver metastases, most are non-functional, but these can often spread silently to the liver. Functional pancreatic NETs can announce themselves earlier and some remain fairly indolent rarely spreading (e.g. insulinomas). Many of these factors statistically guide clues during the diagnostic period as doctors look to tie down primary locations and syndromic connections – it can, however, often be looking for a needle in a haystack. Please note that when NETs spread, they often spread to the liver. That does not mean you have liver cancer. Liver metastases are simply clones of the primary tumour, even when they cannot find that primary tumour.

Surgery remains the only curative option for NETs but it’s true to say this mainly applies to localised tumours at the lower grades. For many, the declaration of liver metastasis means that the cancer is now at an advanced stage and is therefore incurable. However, it is treatable. I’ve discussed surgery in many articles, including the dilemma for doctors and patients in deciding to cut or not to cut. And I have written about my own liver treatment here. For this article, I wanted to focus on the types of liver-directed therapy excluding surgery.

If you can see them, you can treat them

Finding the liver metastases can often be easier than finding the primary, however, some scans or combinations of scans may be necessary to determine the best picture to plan for therapeutic intervention. Many people will have had an ultrasound-guided liver biopsy which is good enough for that purpose but that scan type has a low mean sensitivity in detecting every liver deposit. NET liver metastases are hypervascular so they may look different from normal liver abnormalities if contrast infusion is used during CT. However, to take advantage of their hypervascular nature, scanning using both arterial and portal phases make it less likely that metastases will be missed. Most texts say CT has a sensitivity of around 85% for NET liver metastases. MRI is at least as good as CT for NET liver metastases. Often, somatostatin receptor nuclear scans such as the Octreotide scan or Ga68 PET, can at best confirm the staging or enhance it by finding further and/or smaller deposits.

Clearly, systemic treatment covers the liver too, but liver-directed therapy does what it says on the tin – it directly targets cancer in the liver and is often used to treat NETs that have spread to the liver for a number of reasons including:

• control symptoms caused by too many hormones released by the tumour, especially if somatostatin analogues have stopped working.
• relieve or control the symptoms of advanced neuroendocrine cancer (palliative therapy).
• slow down and control the growth of cancer.
• shrink one or more tumours before surgery/clean up after surgery.

The following liver-directed therapies may be used to treat NETs in the liver. You may have other treatments before or after liver-directed therapy.