HCC Treatment: Resection, Ablation or Liver Transplant

Hepatocellular carcinoma (HCC) can be treated by liver resection, ablation, transarterial chemoembolisation (TACE), radiotherapy, systemic drugs or liver transplant. The right HCC treatment depends on tumour stage and on how well the surrounding liver works. For HCC in a cirrhotic liver, liver transplant surgeon Dr. Ashish George regards upfront transplant as one of the best treatment options, because it removes both the tumour and the diseased liver that produced it.

Dr. Ashish George, Principal Consultant & Unit Head Liver Transplant, Fortis Hospital, Shalimar Bagh, New Delhi, India, set out the decision framework he uses, the transplant criteria and downstaging protocol that widen access to transplant, and how surgeons working without a transplant programme can still offer curative surgery. Diagnosis, screening and tumour markers are covered in the complete guide to the management of primary liver cancers.

The two variables that decide HCC treatment: tumour stage and liver function

The Barcelona Clinic Liver Cancer (BCLC) staging system is the starting framework. What it captures, in Dr. George's summary, is a balance between the tumour and the liver:

• Early, small tumours in a liver with good function can be resected. That means a liver with no background cirrhosis, or a cirrhotic liver in which portal pressures are not high and function is preserved, essentially Child-Pugh class A (the best of the three grades of liver function in cirrhosis).
• Tumours within transplant criteria in a liver that is failing should be offered liver transplant. Raised portal pressures or an elevated bilirubin are markers that liver function is reduced.
• Multifocal tumours that are within transplant criteria can also be offered transplant.

BCLC has since been updated (the 2022 version) with a more detailed algorithm, which Dr. George showed but did not walk through. The core logic carries over: the tumour defines what needs treating, and liver function defines which treatments the patient can tolerate.

Treatment principles: preserve liver function and plan for the long term

Two principles govern every decision.

Preserve liver function. In a patient with cirrhosis, the surgeon cannot remove a large part of the liver. A small tumour that can be resected without sacrificing much liver is resected. A small tumour that is deep-seated, where cutting it out would take most of the liver with it, can instead be treated with microwave ablation, radiofrequency ablation (RFA) or TACE.

Plan beyond the current lesion. Every tumour should go to a multidisciplinary team (MDT) meeting, because the plan has to cover the patient's long-term course, not just the lesion on today's scan.

Resection, ablation, TACE, radiotherapy and drugs: where each fits

Hepatectomy (liver resection). Suitable for early cirrhotics (Child-Pugh A) with preserved liver function and a small, resectable tumour, or for a superficial, peripherally placed tumour.

Ablation. Radiofrequency and microwave ablation destroy the tumour with heat delivered through a needle. They are best suited to small tumours and are minimally invasive, avoiding a laparotomy (open abdominal surgery) or laparoscopic operation. Ablation is used either as a bridge to transplant or as a primary treatment, and for early, small tumours resection and ablation may give equal results.

TACE. Transarterial chemoembolisation delivers chemotherapy into the arteries feeding the tumour and then blocks them. It can be used for slightly larger tumours, for tumour control, and as a bridge to transplant.

Radiotherapy. Stereotactic body radiotherapy (SBRT, precisely targeted high-dose radiation) and transarterial radioembolisation (TARE, radioactive microspheres delivered through the hepatic artery) are the options when, in a cirrhotic patient, the main portal vein is invaded. Surgery is not possible with main portal vein invasion. Instead, TACE treats the primary tumour while SBRT or TARE treats the tumour in the portal vein.

Systemic therapy. Sorafenib and lenvatinib, and more recently immunotherapy with atezolizumab plus bevacizumab, are used for advanced disease. New data suggest these drugs can also serve as downstaging therapy before transplant.

The interventional side of these treatments (how ablation and TACE are performed and selected) is covered from the radiologist's perspective in Dr. Shobhit Singh's articles on liver tumour ablation and TACE and TARE. Indicative costs are listed for hepatectomy and TACE.

Liver resection vs transplant for HCC on cirrhosis

Dr. George describes liver transplant as one of the best treatment options in HCC, for two reasons.

It treats the underlying liver disease. Removing the diseased liver also removes the cause of any symptoms of liver failure the patient has.

It removes the pre-malignant field. Cirrhosis is considered a pre-malignant condition. A tumour treated today by resection, microwave ablation or TACE may be completely ablated, yet there is a fair chance, in Dr. George's figure about 70% over the next five years, that the patient will develop another tumour.

He uses an agricultural image to explain it. A cirrhotic liver is like a fertile field. Remove one tumour and the cells around it retain a higher tendency to mutate into cancer cells. A transplant replaces the whole diseased liver with one that does not carry that risk, so the risk of recurrence may be lower than after resection or ablation alone.

The fallback after a recurrence is a salvage transplant. The difficulty is timing. The second tumour may not be picked up in time, and by then vascular invasion may rule transplant out. That is why Dr. George considers upfront transplant an excellent choice in a patient with cirrhosis, even when the tumour looks resectable.

Milan criteria and expanded transplant criteria for HCC

Transplant criteria define which tumour burdens give results good enough to justify a donor liver.

• Milan criteria, the earliest: a single tumour of up to 5 cm, or up to three tumours each no larger than 3 cm, without vascular invasion or spread outside the liver. Patients transplanted within Milan had very high survival.
• UCSF criteria (University of California, San Francisco), which came next: a single tumour of up to 6.5 cm, or up to three tumours, each no larger than 4.5 cm, with a total tumour diameter of up to 8 cm. Survival was comparable to Milan, so many patients beyond Milan could still be transplanted with very good results.
• Newer expanded criteria from individual hospitals and countries now allow larger tumours and higher tumour burdens to be transplanted, either as the primary treatment or after neoadjuvant (pre-transplant) therapy.

Dr. George's 2024 masterclass, a separate session, discusses the UCSF criteria in the wider context of transplant indications in Liver Transplant for HCC: UCSF Criteria and Downstaging.

Downstaging HCC with portal vein invasion before transplant

Downstaging is treatment given to shrink or stabilise a tumour that is outside transplant criteria, or that has portal venous invasion, so that the patient can then be transplanted. The tools are:

• Immunotherapy.
• Percutaneous ablation.
• TACE for the primary tumour.
• TARE for portal vein invasion.

If the patient achieves stable disease that falls within criteria, liver transplant can be offered. Recurrence rates after transplant are somewhat higher than in patients who were within criteria from the start. Dr. George's argument is that the comparison is the wrong one: the only other option for these patients is best supportive care, which carries a very high long-term mortality.

Grading portal vein invasion: Vp1 to Vp4

Portal vein tumour thrombus is graded by how far up the portal tree it reaches. The Vp classification follows the anatomy from the smallest branches to the main trunk:

• Vp1: a segmental branch is involved.
• Vp2: a sectoral branch is involved (the right anterior or right posterior sectoral branch).
• Vp3: the right or left main portal branch is involved.
• Vp4: the main portal vein is involved.

The grade matters because of what Dr. George offers. A patient with a large primary tumour and Vp1 or Vp2 involvement, and no disease outside the liver, can be offered liver transplant, either upfront or after downstaging. Milan and UCSF both exclude macrovascular invasion, so this is an extended indication offered by experienced transplant centres after careful selection.

The downstaging protocol

The sequence Dr. George described:

1. Rule out extrahepatic disease. Every effort goes into this first.
2. Treat the primary with TACE. For large tumours a single session may not be enough; one, two or three sessions may be needed.
3. Treat the tumour thrombus with SBRT. This applies to thrombus in the sectoral, right or left portal vein. His unit has also used SBRT for a very large primary tumour where the interventional radiologist judged TACE inadvisable.
4. Reassess over 12 weeks. The target is stable disease over three months: no extrahepatic disease, a significant reduction in tumour markers, and no progression within the liver.
5. Transplant the patients who meet that standard.

Surgery for large and non-cirrhotic HCC without transplant access

Doctors at the session described practices where most HCC patients present late, with tumours as large as 10 cm, and where no transplant programme exists. Dr. George's approach starts with one question: is the background liver cirrhotic?

Non-cirrhotic liver. Some patients, including carriers of hepatitis B or C acquired by vertical transmission, have large tumours in an otherwise normal liver. Here Dr. George's unit is extremely aggressive. Extended resections are possible, and the remnant can be enlarged first by portal vein embolisation (blocking the portal supply to the side to be removed, so the side that will remain grows). ALPPS (associating liver partition and portal vein ligation for staged hepatectomy) is another option. The physiological basis is regeneration: in a normal liver, even if almost 80% is removed, the remaining 20% should grow back and take over all the liver's functions. In his practice such patients are uncommon, about 5 in every 100 HCCs.

Cirrhotic liver. Every effort goes into excluding extrahepatic disease. The next step is to grade any portal venous invasion, because patients with Vp1 or Vp2 involvement and no extrahepatic disease remain candidates for downstaging and transplant.

Deep tumours in the liver that will remain. When a second, deep-seated tumour sits in the future liver remnant, intraoperative microwave ablation can treat it while preserving most of the liver tissue. That requires a capable interventional radiologist.

Dr. George's view, offered to surgeons operating under these constraints, is direct: surgery is the only chance of cure in hepatobiliary cancers, and the decision is best made in an MDT around what can be achieved for the patient in that setting.

Drug therapy after resection or transplant for HCC

After resection. Dr. George's unit places most patients on lenvatinib for a long period after resection. This is his unit's practice: adjuvant drug therapy after HCC resection is not yet a guideline standard, because no drug has shown a durable survival benefit in trials.

After transplant. There is usually no separate adjuvant anti-cancer treatment. Instead, the standard immunosuppression is modified. Everolimus, an immunosuppressive drug, has been associated with a lower risk of HCC recurrence after liver transplant. In place of the standard combination of tacrolimus and mycophenolate, his unit uses tacrolimus plus everolimus.

What it takes to build a liver transplant programme

Asked what a centre needs to offer transplant, Dr. George named intent first. Even in India, only a handful of government centres perform liver transplants; the push has come mainly from the private sector, because governments face more pressing problems that need less infrastructure and cost.

The infrastructure is substantial:

• A very good interventional radiologist.
• Good CT and MRI capable of phasic scans.
• An apheresis machine for ABO-incompatible transplants (transplants across blood groups).

Second is mentorship. Surgeons already trained in transplant need to support the first cases so that the skill set transfers. In his experience the programme was surgeon-driven, and radiology, anaesthesia, critical care and hepatology sometimes became the constraints, so every discipline must be equally committed. Hospital management must stand fully behind the team, because transplant demands far more time and effort than routine gastrointestinal or hepatobiliary surgery.

The standard has changed. Death after liver transplant is now the exception: across the board, of 100 transplants perhaps 5 to 7 patients die, and the majority go home walking. That is why Dr. George advises a new programme to work with experienced transplant teams, so that the skills transfer without patients bearing the cost of a learning curve. Indicative figures for liver transplant costs are published separately.

Cholangiocarcinoma, the other primary liver cancer, follows a different surgical logic, covered in cholangiocarcinoma surgery and the Bismuth-Corlette classification. Doctors' questions on recurrence, large tumours and setting up a transplant centre are answered in the Live Discussion.