"Inoperable" does not mean "untreatable"
It’s one of the hardest things to hear. But it almost always means something else: that surgery isn’t the best option right now. This may be due to the number of metastases, their size or location, because there would be little healthy liver left, or because of your overall health.
This is common. According to the literature, only a minority of patients with liver metastases from colon cancer are candidates for surgery at the time of diagnosis. There are other options, and they can be combined. In this guide, we won’t repeat what we’ve already explained about when liver metastases are operated on; here, we’ll discuss what happens when they aren’t.
The first step is to be evaluated by a multidisciplinary team. European guidelines (ESMO, 2026) recommend that all patients with metastatic disease be evaluated by a multidisciplinary team from the time of diagnosis. This team typically includes medical oncology, liver surgery, interventional radiology, radiation oncology, and radiology.
Option 1: Chemotherapy to make the metastases resectable
Sometimes chemotherapy (with or without biologic drugs) reduces the metastases enough to allow for surgery later. This is called conversion therapy. The SEOM describes it as a strategy to attempt surgical resection when the metastases are limited to the liver or lungs.
Some useful things to know:
- According to ESMO guidelines, the maximum response is usually seen around 12–16 weeks. That’s why you’ll be reevaluated with imaging tests on a regular basis.
- The choice of treatment regimen depends on your biomarkers and the tumor’s location. We explain this in the guidelines on KRAS, native RAS and cetuximab/panitumumab, FOLFOX, FOLFIRI, and bevacizumab.
- Just because the lesion “disappears” on a CT scan doesn’t always mean there’s no tumor left. That’s why the team carefully evaluates each case.
Option 2: Local Treatments Targeting the Liver
These are techniques that act directly on the metastases. They are usually used in addition to chemotherapy, not in place of it. They are primarily performed by the interventional radiology department, or by the radiation oncology department in the case of stereotactic radiotherapy.
| Technique | What it involves | Who is typically considered for this |
|---|---|---|
| Thermal ablation (radiofrequency or microwave) | A thin needle is inserted under image guidance, usually through the skin, and the lesion is destroyed using heat. | Small, well-localized metastases. |
| Stereotactic body radiation therapy (SBRT) or brachytherapy | High-dose, highly precise radiation delivered to each lesion. | Lesions that cannot be treated with thermal ablation. |
| Chemoembolization (TACE) | Microspheres containing chemotherapy are delivered through a catheter into the hepatic artery, which also blocks part of the blood supply to the lesion. | Primarily for liver disease, as an adjunct or salvage therapy. |
| Radioembolization (Y-90, SIRT) | Radioactive microspheres are delivered into the liver via the same type of access. | Primarily used for liver cancer that has progressed after chemotherapy. |
| Hepatic Artery Infusion (HAI) | Chemotherapy is administered directly into the artery leading to the liver via a reservoir or pump. | Selected cases, at experienced centers. |
Radiofrequency and Microwave Ablation
ESMO guidelines indicate that, in patients with inoperable liver-only metastases, thermal ablation may be considered for small metastases. In some cases, it is used in conjunction with surgery to treat lesions that cannot be removed.
A phase II randomized trial (CLOCC) compared radiofrequency plus chemotherapy versus chemotherapy alone in inoperable metastases. With nearly 10 years of follow-up, the radiofrequency group had better overall survival and better progression-free survival. It is a small trial, so it does not allow for definitive conclusions about outcomes for any patient.
Some advantages of ablation are that it is less invasive than surgery, it preserves healthy liver tissue, and it can be repeated if new lesions appear. An important caveat: it does not always achieve the same results as surgery, which remains the first-line local treatment when possible. And it is not recommended as a local palliative treatment when there is extensive disease outside the liver.
Stereotactic Radiotherapy
ESMO guidelines recommend it for inoperable liver metastases that cannot be treated with thermal ablation, for example, due to their location. It is another way to target the lesion without surgery. Not all hospitals offer this technique to the same extent.
Chemoembolization and radioembolization
These are considered for patients with disease predominantly in the liver. The 2026 ESMO guidelines propose them as intensification or as a rescue treatment, with a low level of evidence (III, C). In other words, there are fewer robust studies supporting them than there are for surgery or ablation.
- Radioembolization: In a small study of patients with liver-only metastases who had already tried available chemotherapy, it delayed disease progression in the liver. The 2022 ESMO guidelines include these as non-curative options.
- Chemoembolization: The data come primarily from microspheres loaded with irinotecan. Randomized studies have design limitations. U.S. guidelines (ASCO) do not include it, while ESMO considers it for patients who have failed previous treatments and have good liver function.
Before radioembolization, tests are usually performed to ensure that the microspheres will not travel to other organs, such as the lungs. This is one of the reasons why it is not suitable for everyone.
Hepatic Artery Chemotherapy
It is administered via reservoirs or pumps placed surgically or percutaneously. European experience is based primarily on intra-arterial oxaliplatin combined with intravenous chemotherapy. NCCN patient guidelines warn that this procedure should only be performed by an experienced team. For this reason, it is not available at all centers.
Option 3: Liver transplant, only in very select cases
The 2026 ESMO guidelines list liver transplantation plus chemotherapy as a curative-intent option for very select patients with metastases limited to the liver who will never be eligible for surgery. It requires strict criteria: among others, a BRAF-wild-type tumor, CEA below a certain threshold, a primary tumor that has already been removed, and stable disease control with chemotherapy. In practice, this is rare and is evaluated at highly specialized centers. Ask if you might be a candidate, but don’t assume this is the norm.
How the decision is made about your treatment options
There is no single “best” approach for everyone. It depends on:
- How many metastases you have, their size, and their location.
- Whether there is disease outside the liver (lung, peritoneum).
- How the tumor has responded to chemotherapy.
- Your liver function and overall health.
- Your biomarkers (NGS, BRAF, MSI).
- What’s available at your hospital and what you want.
You may also be offered a clinical trial. And if you’re unsure what to do, you have the right to a second opinion. It makes sense to seek one from a center with a liver surgery unit and interventional radiology department.
Questions to Ask During Your Appointment
- Why aren’t they operable in my case? Could they be operable after chemotherapy?
- Has my case been reviewed by a multidisciplinary team?
- Would ablation be effective for me? What is the size and location of my lesions?
- What is the goal of treatment: to cure the disease, control it, or buy time while maintaining quality of life?
- Is this procedure performed here, or would I need to be referred to another center?
- What are the risks, and how would I recover?
Risks and When to Seek Medical Attention
No procedure is risk-free. The literature describes infections and abscesses in the liver following ablation, as well as, very rarely, damage to nearby structures. If the lesion is near the diaphragm, the heat may affect the pericardium. Fatigue, nausea, and abdominal pain are common after radioembolization, and bilirubin levels may sometimes be altered.
Each hospital will provide its own instructions. As a general guideline, notify your care team or go to the emergency room if, after a procedure, you notice:
- Fever or chills. If you are also undergoing chemotherapy, read the guide on febrile neutropenia.
- Severe or worsening abdominal pain.
- Yellowing of the skin or eyes, or very dark urine.
- Uncontrollable vomiting.
- Difficulty breathing, chest pain, or severe dizziness.
- Bleeding or swelling at the injection site.
If in doubt, call. It’s better to check in once too often than not enough.
A final message, in all honesty
For some patients, these techniques control the disease for a long time and maintain a good quality of life. For others, the benefit is limited. No one can promise you specific results, which is why it’s so important that they explain the purpose of each step to you. Following your oncologist’s instructions and discussing any concerns with them is the best way to take care of yourself. If the journey becomes difficult, palliative care can support you from the very beginning, alongside your treatment.