Expanded living‐donor liver transplantation criteria for patients with hepatocellular carcinoma based on the Japanese nationwide survey: the 5‐5‐500 rule ‐ a retrospective study

Abstract

Summary Expansion of the liver transplantation indication criteria for patients with hepatocellular carcinoma (HCC) has long been debated. Here we propose new, expanded living‐donor liver transplantation (LDLT) criteria for HCC patients based on a retrospective data analysis of the Japanese nationwide survey. A total of 965 HCC patients undergoing LDLT were included, 301 (31%) of whom were beyond the Milan criteria. Here, we applied the Greenwood formula to investigate new criteria enabling the maximal enrollment of candidates while securing a 5‐year recurrence rate (95% upper confidence limit) below 10% by examining various combinations of tumor numbers and serum alpha‐fetoprotein values, and maintaining the maximal nodule diameter at 5 cm. Finally, new expanded criteria for LDLT candidates with HCC, the 5‐5‐500 rule (nodule size ≤5 cm in diameter, nodule number ≤5, and alfa‐fetoprotein value ≤500 ng/ml), were established as a new regulation with a 95% confidence interval of a 5‐year recurrence rate of 7.3% (5.2–9.3) and a 19% increase in the number of eligible patients. In addition, the 5‐5‐500 rule could identify patients at high risk of recurrence, among those within and beyond the Milan criteria. In conclusion, the new criteria – the 5‐5‐500 rule – might provide rational expansion for LDLT candidates with HCC.

The history of liver surgery: Achievements over the past 50 years

“…However, none have become widely used, with the exception of the University of California San Francisco (UCSF) criteria . There were calls for the creation of Japanese criteria to broaden the indications for liver transplantation, most of which referred to living‐donor liver transplantations, and recently, the 5‐5‐500 criteria were announced . These criteria were statistically determined based on data from more than 1000 nationwide cases of living‐donor liver transplantations for patients with liver cancer, including individuals that fulfilled certain conditions (maximum tumor size of 5 cm, a 70% or higher 5‐year survival rate, and a 10% or lower 5‐year incidence of recurrence), and were also based on the optimal criteria for alpha‐fetoprotein (AFP) or protein induced by vitamin K absence or antagonist‐II (PIVKA‐II).…”

Liver Transplantation for Locally Advanced Hepatocellular Carcinoma

“…26 Based on these results, the recently expanded criteria set the tumor diameter limit between 5 and 6.5 cm. [21][22][23][24][27][28][29][30] On the other hand, the influence of nodule numbers for microvascular invasion showed nonlinear behavior. 24 The incidence of vascular invasion was in direct proportion up to nodule number three, and then the increasing slope became moderate.…”

“…AFP values, combined with the expanded criteria, enabled the prediction of tumor recurrence and prognosis to be more accurate. [28][29][30][33][34][35] The appropriate cutoff value of AFP is still under investigation, but there is no doubt that AFP is essential to the prediction models for HCC recurrence after liver transplantation. To date, UNOS allocation and the French model 29 adopted the AFP cutoff value as less than 1,000 ng/mL, and other prediction models, such as the TTV/AFP model 33 and the Hangzhou criteria 28 set a cutoff value at less than 400 ng/mL.…”

Recent advances in liver transplantation for cancer: The future of transplant oncology

“…Recently, the 5-5-500 criteria (tumour size ≤5 cm, tumour number ≤5, and AFP ≤500 ng/ml) was associated with a 5-year recurrence rate of 7.3% in patients treated with LDLT. 22 The use of 18 F-fluorodeoxyglucose positron-emission tomography/CT ( 18 FDG-PET/CT) has been correlated with HCC recurrence and increasingly used as a tool for patient selection. 23,24 Further research is still needed to be able to incorporate PET/CT widely into clinical practice.…”