Liver Cancer Treatment by Stage

Most liver cancer grows inside a liver that is already scarred. So the team is managing two things at once: the tumour, and the liver holding it.

That is why a plan that would suit the tumour can still be unsafe. If the liver has little reserve left, cutting part of it out, or blocking the blood supply to a tumour, can tip the whole organ into failure.

This page explains how those two questions are weighed. It is not advice about your own care.

Most cancers are staged by how far they have spread. Liver cancer usually is not.

NCI calls the Barcelona Clinic Liver Cancer system, or BCLC, the most accepted staging system for hepatocellular carcinoma. Evidence from an American group showed it separated outcomes better than other systems.

BCLC has five stages, 0 and A through D. It combines three things a stage number alone leaves out:

• How large and how many the tumours are, and whether blood vessels are involved.
• How well the liver is working.
• How well the person is in daily life.

The system then links each stage to the treatments that fit it. Early stages point toward treatment aimed at cure. Later stages point toward treatment aimed at control.

Liver function is scored with Child-Pugh. It uses bilirubin, albumin, clotting time, fluid in the abdomen and confusion. The classes are A, B and C, with A the best preserved.

That letter quietly decides a lot. NCI notes the trials that established today's first-line systemic drugs enrolled people with Child-Pugh class A function. Chemoembolization is relatively contraindicated when there is portal hypertension, a clot in the portal vein, or jaundice, and in a decompensated liver it can raise the risk of liver failure.

Ask which class you are in, and whether it is expected to change.

About 30 percent of hepatocellular carcinoma is found as a single mass or a few small ones, without major vessel involvement. NCI lists surveillance, surgical resection, liver transplant, ablation and radiation therapy as options here.

Resection means cutting the tumour out. It suits people with localised disease and enough working liver left over.

Transplant replaces the tumour and the diseased liver together. It is often the best option when cirrhosis is decompensated and there is one lesion under 5 cm, or up to three lesions each 3 cm or under.

Ablation destroys the tumour where it sits. Radiofrequency ablation and alcohol injection are both used. In randomised trials in people with Child-Pugh class A cirrhosis, radiofrequency ablation gave better complete response and fewer local recurrences than alcohol injection, and needed fewer sessions.

NCI reports that five-year overall survival after transplant for early disease is 44 to 78 percent, and 27 to 70 percent after resection. Only 10 to 23 percent of people are candidates for treatment aimed at cure when they are diagnosed.

The Milan criteria decide who can be considered. A single tumour smaller than 5 cm qualifies. So do two or three tumours each smaller than 3 cm. NCI reports about 70 percent five-year overall survival for people who meet them, and says the data do not consistently support widening them.

The limit is supply. There are not enough donor livers, and that alone restricts how often this option is available. Local treatment is sometimes used to hold the cancer steady while someone waits.

Normal liver tissue gets most of its blood from the portal vein. Liver tumours get theirs mainly from the hepatic artery, and they tend to be richly supplied.

That difference is what embolization exploits. A catheter is threaded to the artery feeding the tumour and the flow is blocked. When chemotherapy is delivered at the same time, it is called chemoembolization, or TACE.

NCI reports a meta-analysis showing TACE improves survival compared with supportive care alone. There is no agreed standard for which agent, dose or schedule to use.

Radiation has a role too. In the NRG/RTOG 1112 trial, adding stereotactic body radiation therapy to sorafenib gave a median overall survival of 15.8 months against 12.3 months, a difference that was not statistically significant. NCI says radiation for liver cancer can be given with curative or with palliative intent, and lists it among the standard options.

Sorafenib was the standard for years. In the SHARP trial it gave a median overall survival of 10.7 months against 7.9 months on placebo.

Two combinations have since beaten it.

• Atezolizumab with bevacizumab. In IMbrave150, median overall survival was 19.2 months against 13.4 months with sorafenib. It is FDA-approved for unresectable or metastatic liver cancer in people who have not had systemic therapy before.
• Durvalumab with tremelimumab. In HIMALAYA, median overall survival was 16.4 months against 13.8 months with sorafenib. Tremelimumab is FDA-approved in combination with durvalumab for unresectable liver cancer.

Nivolumab with ipilimumab is FDA-approved as a first-line treatment for unresectable or metastatic liver cancer. Lenvatinib is FDA-approved as first-line treatment for unresectable disease.

Bleeding risk shapes the choice. The IMbrave150 trial excluded people with untreated or partly treated varices in the oesophagus or stomach, because bevacizumab raises bleeding risk. Ask whether your varices have been checked.

One caution. NCI's summary also lists atezolizumab with cabozantinib as a first-line option. In the COSMIC-312 trial that combination improved progression-free survival but not overall survival, and it is not FDA-approved for liver cancer.

NCI lists regorafenib, cabozantinib and ramucirumab as second-line targeted options.

The labels are more specific than the list. Regorafenib and cabozantinib are both approved for liver cancer previously treated with sorafenib. Ramucirumab is approved only for people whose alpha-fetoprotein is 400 ng/mL or higher and who have had sorafenib.

Pembrolizumab appears in NCI's second-line list without qualification. Its current FDA label is narrower. It covers liver cancer secondary to hepatitis B, in people who have had prior systemic therapy that did not contain a PD-1 or PD-L1 drug. Where a summary and a label disagree, that is worth raising with your team.

SEER reports five-year relative survival of 21.9 percent for liver and intrahepatic bile duct cancer for 2016 through 2022. By stage at diagnosis it is 37.4 percent for localised, 13.4 percent for regional and 3.6 percent for distant disease.

Those figures combine liver cancer with bile duct cancer, and they do not separate people by liver function. Two people with the same stage can have very different options.

Most people treated for liver cancer also have cirrhosis, and the liver failing can be the more urgent problem.

• Call 911 or go to an emergency department if you vomit blood, or pass black tarry stools, or bleed from the back passage. MedlinePlus lists these as emergencies in cirrhosis. Bleeding from swollen veins in the gullet is fast.
• Call 911 or go to an emergency department if you become confused, hard to rouse, or your alertness gets worse. MedlinePlus lists a change in alertness as an emergency here.
• Call your care team the same day if your abdomen swells, or the swelling suddenly gets worse.
• Call your care team the same day if the yellow in your eyes or skin is new, or deepening.
• Call your care team the same day if you have a temperature of 100.4°F (38°C) or higher, severe abdominal pain, or new breathlessness. A mild fever in the days after chemoembolization is often post-embolization syndrome, which is expected and not dangerous by itself.
• But treat that fever as an emergency if it arrives while you are on systemic chemotherapy, or your team has told you your white cell count is low. In that situation the CDC rates fever a medical emergency: phone the oncology line at once, whatever the hour, and if nobody answers quickly, go to an emergency department rather than waiting on a call back.
• Call your care team within a day or two if your weight climbs by a few pounds over a few days, or your ankles start to swell. That is often fluid, and it is easier to treat early.

Liver Cancer, Liver Cancer Stages, What Does LI-RADS Mean?, and Clinical Trial vs Standard Treatment.

• https://www.cancer.gov/types/liver/hp/adult-liver-treatment-pdq
• https://www.cdc.gov/cancer-preventing-infections/patients/fever.html
• https://seer.cancer.gov/statfacts/html/livibd.html
• https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=6fa682c9-a312-4932-9831-f286908660ee
• https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=6690679c-be2f-4588-a2e4-89fff74dd6be
• https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c6080942-dee6-423e-b688-1272c2ae90d4
• https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9333c79b-d487-4538-a9f0-71b91a02b287
• https://medlineplus.gov/ency/article/000255.htm