Tumor Count and MELD Score Guide Surgery Choice for Intermediate Liver Cancer

Hepatocellular carcinoma, the most common primary cancer of the liver, remains one of the leading causes of cancer-related death both in Taiwan and around the world, and the clinical dilemma it poses for patients with intermediate-stage disease has long frustrated hepatologists and surgeons alike. For patients classified as stage B under the Barcelona Clinic Liver Cancer staging system, international guidelines have traditionally pointed away from surgery and toward transarterial chemoembolization, a catheter-based therapy that delivers chemotherapy directly into the arteries feeding the tumor while cutting off its blood supply. Yet liver resection, the surgical removal of tumor-bearing liver tissue, has never disappeared from practice, because it offers something no embolization, ablation, or systemic drug can: the physical removal of large tumors in a single operation. A new retrospective study conducted at Kaohsiung Chang Gung Memorial Hospital in Taiwan now proposes a deceptively simple way to decide, before the first incision or the first catheter pass, which intermediate-stage patients truly benefit from surgery and which are better served by embolization.

The study, published in the open-access journal Cancer Reports, rests on two variables that are already measured in every hepatocellular carcinoma workup: the number of tumors visible on imaging and the Model for End-Stage Liver Disease score, a laboratory index calculated from bilirubin, creatinine, and the international normalized ratio of prothrombin time that quantifies the functional reserve of a cirrhotic or damaged liver. The researchers drew on the rationale of the Japanese Society of Hepatology guidelines, which recommend considering liver resection for patients with multiple tumors when the tumor number is three or fewer, and reserving non-surgical treatments for patients with more than three tumors. They also incorporated the findings of a previous Italian study showing that a MELD score above nine signals an inadequate liver function reserve in patients undergoing liver resection, and that such a score was independently associated with postoperative liver decompensation, with an odds ratio of 2.26, a 95 percent confidence interval of 1.10 to 4.58, and a p value of 0.02.

From these two parameters the investigators constructed a two-tier classification of intermediate-stage disease that they labeled BCLC B1 and BCLC B2. Patients in the B1 category had to meet both criteria simultaneously, meaning a tumor number of three or fewer and a MELD score of nine or below, and these were defined as the ideal candidates for liver resection. Patients in the B2 category needed to satisfy only one of the two criteria, and these were defined as nonideal candidates for surgery. The cohort consisted of patients diagnosed with hepatocellular carcinoma between 2011 and 2021 who were managed at the study institution, all of whom had Child-Pugh class A liver function, the mildest functional class, and who had undergone either liver resection or transarterial chemoembolization. The protocol was approved by the Institutional Review Board of Kaohsiung Chang Gung Memorial Hospital under reference number 202201189B0, conformed to the Declaration of Helsinki, and the requirement for individual informed consent was waived.

The enrollment process captured a rich set of baseline variables for each patient, including age, sex, alpha-fetoprotein level, hepatitis B surface antigen status, antibody test results for hepatitis C virus, total bilirubin, creatinine, international normalized ratio, Child-Pugh classification, and MELD score. Under the staging definitions used in the study, BCLC stage B patients were those with Child-Pugh A or B liver disease and multifocal hepatocellular carcinoma beyond the Milan criteria, who did not have cancer-related symptoms and did not show macrovascular invasion or extrahepatic spread. The treatment algorithm at the institution reflected the realities of clinical practice in Taiwan: liver transplantation was an option for patients whose tumor burden fell within the University of California San Francisco criteria with a low alpha-fetoprotein level and clinically significant portal hypertension, the latter defined by a platelet count below ten to the ninth per liter with splenomegaly, the presence of varices, or portosystemic collateral vessels. Lobectomy was considered for tumors confined to one lobe, single-needle radiofrequency ablation was applied to multiple tumors smaller than three centimeters, and multipolar radiofrequency ablation was used for multiple tumors in which at least one measured between three and five centimeters. External beam radiation, systemic chemotherapy, or targeted therapy with sorafenib or lenvatinib was reserved for infiltrative hypovascular tumors or a tumor burden too high for embolization. Notably, targeted therapies and selective internal radiation therapy were not reimbursed by Taiwan’s National Health Insurance for patients with BCLC stage B disease, which constrained how often these modalities could be deployed.

When the researchers compared the baseline characteristics of the liver resection and chemoembolization subgroups, most variables were well balanced. Age, sex, the diameter of the largest nodule, alpha-fetoprotein level, and hepatitis B surface antigen positivity did not differ significantly between the groups. One exception stood out: the proportion of patients testing positive for hepatitis C virus antibodies was lower in the resection subgroup than in the embolization subgroup, a difference that reached statistical significance with a p value of 0.046. In one comparison of patient subgroups, the two arms also did not differ in alpha-fetoprotein levels of at least 400 nanograms per milliliter, which were recorded in 25 of 84 patients, or 29.8 percent, in one arm and 12 of 64 patients, or 18.8 percent, in the other, with a p value of 0.125.

The survival analysis produced the study’s central finding. Among patients classified as BCLC B1, the ideal surgical candidates, the median overall survival of patients undergoing liver resection was not reached during the observation period, while patients receiving transarterial chemoembolization survived a median of 3.9 years, with an interquartile range of 2.8 to 4.9 years. The difference was statistically significant, with a p value of 0.007. Strikingly, no patients in this group died within 90 days of treatment, underscoring that carefully selected surgical candidates not only lived longer but did so without an early postoperative mortality penalty. The Kaplan-Meier estimator and the log-rank test were used for these comparisons, all p values were two-tailed, and a p value below 0.05 was considered statistically significant.

The picture was different in the BCLC B2 group, the nonideal surgical candidates. There, two patients, or 2.5 percent, of those undergoing liver resection and four patients, or 1.9 percent, of those receiving chemoembolization died within 90 days of treatment, a difference that was not statistically significant with a p value of 0.671. The authors concluded from the combined evidence that patients with BCLC B1 disease are ideal candidates for liver resection, whereas those with BCLC B2 disease are not. This conclusion challenges the reflexive exclusion of surgery from intermediate-stage disease and, equally, challenges the assumption that all intermediate-stage patients are alike.

The study also engaged directly with competing frameworks for subdividing stage B disease. Spanish and Japanese investigations have used the up-to-seven criteria, in which the sum of tumor number and the size of the largest tumor in centimeters must not exceed seven, combined with Child-Pugh scores of 5 to 9, to stratify candidates. One cited study found a five-year recurrence rate of 25 percent for liver resection versus 60 percent for chemoembolization in a subgroup defined as Child-Pugh score 5 to 7 and within up-to-seven, with survival outcomes not differing between other subgroups, and concluded that resection provided better overall survival for that subgroup while survival was comparable for the others. A Korean study took a different tack, defining B2 disease as two to four oligonodular tumors with a largest tumor smaller than 10 centimeters, and found that resection produced better overall survival than embolization in that group, with a p value of 0.014, while survival did not differ significantly in the other groups. The Taiwanese authors argued that the up-to-seven criteria are not suitable for selecting patients for resection, because the very advantage of surgery is the removal of large tumors; in other words, tumor size should not disqualify a patient from resection. They illustrated the point with a concrete contrast: a patient with multiple small tumors, up to four in number with the largest measuring three centimeters and confined to one lobe, would fall within up-to-seven and be deemed an ideal resection candidate by the Spanish and Japanese criteria, yet in the authors’ experience such a patient would not be recommended for surgery. Conversely, their own tumor-number-based approach aligns with the Korean finding that resection suits patients with two to four tumors but not those with five or more.

The authors acknowledged that a proportion of BCLC B2 patients in their cohort may have had diffuse infiltrative hepatocellular carcinoma or a tumor burden too high for embolization, meaning that neither resection nor chemoembolization was truly suitable for them. Because systemic therapies for BCLC stage B disease were not reimbursed by Taiwan’s National Health Insurance, very few patients at this stage received such treatments, leaving a therapeutic gap that the study could not fill. The limitations of the work were stated plainly: it was retrospective and monocentric; it lacked data on severe comorbidities; cirrhosis data were not presented because the registry defined cirrhosis histologically for surgical patients and by imaging for non-surgical patients, and image-based definitions can be vague and subjective; and postoperative complication data, which are important for treatment decisions, were not available. The investigators also did not perform propensity score matching between the two treatment arms, because the groups had similar characteristics except for the lower prevalence of hepatitis C positivity among resection patients.

Even with those caveats, the study’s contribution is a practical one. By using just two variables that are available before any treatment begins, the image-defined tumor number and the MELD score, clinicians can preoperatively determine which subgroup of BCLC stage B patients should undergo liver resection and which should be directed toward transarterial chemoembolization. In an era when treatment options for intermediate-stage liver cancer are multiplying, from radioembolization to multipolar ablation to systemic therapy, a simple, reproducible two-parameter rule offers a way to bring order to a contested clinical space, and it gives surgeons and interventional radiologists a shared, evidence-based language for one of hepatocellular carcinoma’s most persistent decisions.

Subject of Research: Selection criteria using tumor number and MELD score for liver resection versus transarterial chemoembolization in intermediate-stage hepatocellular carcinoma

Article Title: Tumor Number and Model for End‐Stage Liver Disease Score as Selection Criteria for Resection or Embolization of Intermediate‐Stage Hepatocellular Carcinoma

Article References: Yen, Y.-H., Yong, C.-C., Liu, Y.-W., Li, W.-F., Wang, C.-C., & Lin, C.-Y. (2026). Tumor Number and Model for End‐Stage Liver Disease Score as Selection Criteria for Resection or Embolization of Intermediate‐Stage Hepatocellular Carcinoma. Cancer Reports, 9(9), Article e70697. https://doi.org/10.1002/cnr2.70697

Image Credits: AI Generated

DOI: 10.1002/cnr2.70697

Keywords: hepatocellular carcinoma, liver resection, transarterial chemoembolization, MELD score, BCLC staging, tumor number, overall survival, Child-Pugh class A, Taiwan, liver function reserve, up-to-seven criteria, retrospective study