What stage IV means
The cancer has spread beyond the colon and formed metastases in another organ. In colorectal cancer the most common sites are the liver, the lungs and the peritoneum (the lining of the abdomen); less often, distant lymph nodes, bones or ovaries. Around 1 in 5 people already has metastases at diagnosis, and others develop them after initial treatment.
A distinction is made between IVA (one organ), IVB (more than one) and IVC (peritoneum). But what really matters for decisions is something else: whether the metastases can be removed or not.
Not one disease: three situations
- Resectable oligometastatic disease: few metastases, in one organ (mainly liver or lung), which can be removed surgically or destroyed by ablation. Here the aim is cure, and it is achieved in a significant proportion of cases. Read our guide on liver metastases.
- Potentially resectable: too many or badly placed now, but which might shrink with intensive chemotherapy and be operated on later ("conversion"). Reassessed with CT every 2-3 months.
- Widespread disease: multiple metastases in several organs. The aim is to control the disease for as long as possible, with the best quality of life, moving from one treatment to the next. More and more people live for years in this situation.
This classification should be made by a multidisciplinary tumour board including liver and thoracic surgeons. If you are told "it is not operable" without a liver surgeon having looked at it, ask for a review or a second opinion.
The molecular profile leads
Before choosing treatment, the tumour should be tested for RAS (KRAS/NRAS), BRAF, MSI/MMR and HER2. Each result opens or closes doors:
| Result | What it implies |
|---|---|
| MSI-H / dMMR | Immunotherapy (pembrolizumab) as first option |
| RAS wild-type, left-sided colon | Chemotherapy + anti-EGFR (cetuximab or panitumumab) |
| RAS mutated | Chemotherapy + bevacizumab; targeted drugs exist for G12C |
| BRAF V600E | Encorafenib + cetuximab (with or without chemotherapy depending on the line) |
| HER2 positive (RAS wild-type) | Anti-HER2 therapies (tucatinib + trastuzumab, others) |
| NTRK (very rare) | TRK inhibitors |
How treatment is organised: lines
Metastatic disease is treated in lines: one combination until it stops working or is not tolerated, then the next.
- First line: chemotherapy (FOLFOX, FOLFIRI, CAPOX; FOLFOXIRI in young, fit people when a rapid response is needed) combined with an antibody according to the molecular profile. In MSI-H, immunotherapy.
- Maintenance: after 4-6 months, if the disease is controlled, treatment is usually lightened (for example capecitabine + bevacizumab) to rest from the more toxic drugs.
- Second line: the chemotherapy is switched (from oxaliplatin to irinotecan or the reverse) and often the antibody too.
- Third line and beyond: trifluridine/tipiracil with bevacizumab, regorafenib, fruquintinib; targeted therapies if there is a target; and clinical trials, which at this stage are a first-rate option, not a last resort. Find those open in Spain with our guided trial finder.
In specific situations local treatments are also used: surgery, ablation, high-precision radiotherapy (SBRT), radioembolisation or HIPEC for the peritoneum.
Prognosis, honestly
Twenty-five years ago median survival in metastatic disease was one year. Today, with current combinations, medians exceed 30 months in trials, and in specific subgroups (MSI-H with immunotherapy, resected liver metastases) a proportion of people live many years or are cured. Medians are the midpoint of thousands of very different people: they do not say what will happen to you. Your molecular profile, your general health, where the metastases are and how you respond to the first treatment weigh far more than the overall figure.
Supportive care from day one
"Palliative care" does not mean "there is nothing more to be done": it is the team that controls pain, nausea, tiredness, anxiety and paperwork, alongside chemotherapy. It has been shown that people who receive it from the start live better and, in some studies, longer. Ask to be referred early, not at the end.
What to ask at your appointment
- Where exactly are my metastases? Are they resectable, potentially resectable or not?
- Have RAS, BRAF, MSI and HER2 been tested? What are the results?
- What is the aim of this treatment: to cure, to try to make it operable, or to control?
- Has my case been discussed at the tumour board with liver/thoracic surgeons?
- Are there clinical trials for my situation now, not only when the treatment fails?
