ILCA Symposium 2: Controversies in Liver Cancer (Pros and Cons Session)
Chairs: Peter R. Galle, MD (Germany) and Morris Sherman, MD, PhD (Canada)
01-A: Resection vs. Ablation in Very Early HCC
Sasan Roayaie, MD (USA)
During this debate, Dr. Roayaie will review the relevant literature on the results obtained from ablation as well as resection of HCC smaller than 2 cm. He will also review the randomised controlled trial that compare resection and ablation with a particular emphasis on results for smaller tumours. At the conclusion of the session, participants will hopefully be able to reach their own conclusions regarding the relative utility of ablation versus resection in patients with small HCC.
01-B: Resection vs. Ablation in Very Early HCC
Masatoshi Kudo, MD, PhD (Japan)
Liver Cancer Study Group of Japan (LCSGJ) started nationwide surveys in 1965 and has prospectively collected data on patients with hepatocellular carcinoma (HCC). According to LCSGJ nationwide survey report during 6 years (January 2000 to December 2005), 1581 Child-pughA patients with HCC < 2cm received resection, 2156 Child- pughA patients with HCC < 2cm received radiofrequency ablation (RFA) and 766 Child-pughA patients with HCC < 2cm received percutaneous ethanol injection (PEI). In order to match the background characteristics of the patients, propensity score analysis has been applied. The hazard ratio for death in the resection group was 0.861 (0.637-1.166, P=0.3335) relative to that in the RFA group and 0.751 (0.514-1.096, P=0.1381). In conclusion, in patients with well preserved liver function (Child-pughA) and very early stage HCC (< 2cm), RFA and PEI showed a similar outcome to resection. Therefore, less invasive treatment modality such as RFA is a choice of treatment for very early stage HCC.
02-A: Does Interferon Prevent Recurrence after Resection? Yes/No
Pierre-Alain Clavien, MD, PhD (Switzerland)
A combined antiviral and tumoricidal effect of interferon (IFN) is assumed to occur after resection of hepatocellular carcinoma (HCC). This double action of IFN is believed to be the principal mechanism underlying the prevention of HCC recurrence in patients with viral hepatitis (HBV and HCV). However the routine administration of IFN in this setting has only slowly gained uniform acceptance because of a variety of side-effects and conflicting data.
A multitude of randomised controlled trials have been performed analysing the effect after curative resection of adjuvant IFN on overall survival and tumour recurrence in patients with both HBV and HCV hepatitis. Meta-analysis including over 10 RCTs has found that IFN has a significant beneficial effect after curative treatment of HCC in terms of both survival and tumour recurrence. This benefit seems stronger for patients with HCV, patients with good tolerance, patients with sustained virological response and longer follow-u. Moreover it only prevents development of a new focus of HCC at a site different from the initial site.
03-A: Liver Transplant beyond Milan? Yes/No
Francis Yao, MD (USA)
- The Milan criteria (1) currently remain the benchmark for the selection of candidates with hepatocellular carcinoma (HCC) for liver transplant (LT) (2, 3). Some have suggested that a “controlled” or modest expansion of tumour size could achieve post-transplant survival comparable to or only slightly below that with Milan criteria (Table 1 and 2).
- Expanded criteria should be evaluated based on pre-operative imaging rather than explants tumour pathology.
- Among the proposed expanded criteria, only the University of California, San Francisco (UCSF) criteria (4, 8) have been independently validated.
- Mazzaferro et al. (13) proposed the up-to-7 criteria based on explant pathologic data collected in a registry format (Metro-ticket) involving 1112 patients.
- Serum alpha-fetoprotein (AFP) level is increasingly recognised as an important prognostic factor that should be incorporated into expanded criteria (14).
- The most clinically relevant question is whether expanded criteria can result in survival after deceased donor liver transplant that is deemed acceptable by the transplant community to justify utilisation of a scarce resource (2, 3). A key to this debate is the concept of a minimal survival threshold with expanded criteria that must be achieved without causing harm to other patients on the transplant waiting list (15).
- According to recommendations from a recent International Consensus Conference on Liver Transplant for HCC (3), expansion of transplant criteria for HCC may be considered on the basis of several studies showing comparable survival, if the waiting list dynamics allow it without causing undue prejudice for those with a better prognosis.
- Tumour down-staging is a process involving expanded criteria and the effects of loco-regional therapy. It may be an alternative to simply expanding the tumour size limits in lieu of loco-regional therapy, since response to down-staging treatment may also serve as a prognostic marker and a tool to select a subgroup of patients with more favorable tumour biology who will likely do well after LT (2, 16). According to a recent international consensus conference (3), LT after successful down-staging should achieve a 5-year survival comparable to that of HCC patients who meet the criteria for LT without requiring down-staging.
03-B: Liver Transplant for HCC Should not be Expanded beyond Milan Criteria
Julie Heimbach, MD (USA)
In the United States in 2012, nearly 28% of livers were allocated to patients with an HCC MELD exception score.1 Additionally, waitlist drop-out rates are significantly lower and transplant rates are higher for patients with HCC MELD exception score compared non-HCC patients. 2,3 Radiographic criteria for accurate staging of HCC are imprecise and have led to patients being both over and under-staged4. While recent policy changes have occurred which may improve this situation, expansion of criteria beyond Milan to UCSF to other proposed criteria may lead to lead to even greater inaccuracy. While outcomes for transplantation for patients within Milan Criteria are excellent, especially by the standards of other available oncologic treatments, they are still inferior to transplantation for other diagnoses5. Expanding to beyond Milan criteria will not improve outcomes, and will more likely lead to slightly worse outcomes. Given the large numbers of patients already transplanted for HCC, and the greater access to transplantation that patients with HCC already enjoy in the United States, even a slight decrease in outcomes for patients transplanted beyond Milan criteria is hard to accept given the need to maximise outcomes of a scare resource.