Analysis of Liver Resection Versus Liver Transplantation on Outcome of Small Intrahepatic Cholangiocarcinoma and Combined Hepatocellular‐Cholangiocarcinoma in the Setting of Cirrhosis

Abstract

This multicenter study compares the outcomes of patients with cirrhosis undergoing liver transplantation (LT) or liver resection (LR) between January 2002 and July 2015 who had intrahepatic cholangiocarcinoma (iCCA) or combined hepatocellularcholangiocarcinoma (cHCC-CCA) found incidentally in the native liver. A total of 49 (65%) LT and 26 (35%) LR patients with cirrhosis and histologically confirmed iCCA/cHCC-CCA ≤5 cm were retrospectively analyzed. LT patients had significantly lower tumor recurrence (18% versus 46%; P = 0.01), for which the median diameter of the largest nodule (hazard ratio [HR], 1.07; 95% confidence interval [CI], 1.02-1.12]; P = 0.006) and tumor differentiation (HR, 3.74; 95% CI 1.71-8.17; P = 0.001) were independently predictive. The LT group had significantly higher 5-year recurrence-free survival (RFS; 75% versus 36%; P = 0.004). In patients with tumors >2 cm but ≤5 cm, LT patients had a lower recurrence rate (21% versus 48%; P = 0.06) and a higher 5-year RFS (74% versus 40%; P = 0.06). Independent risk factors for recurrence were LT (protective; HR, 0.23; 95% CI, 0.07-0.82; P = 0.02), the median diameter of the largest nodule (HR, 1.10; 95% CI, 1.02-1.73; P = 0.007), and tumor differentiation (HR, 4.16; 95% CI, 1.37-12.66; P = 0.01). In the LT group, 5-year survival reached 69% and 65% (P = 0.40) in patients with tumors ≤2 cm and >2-5 cm, respectively, and survival was also comparable between iCCA and cHCC-CCA patients (P = 0.29). LT may offer a benefit for highly selected patients with cirrhosis and unresectable iCCA/cHCC-CCA having tumors ≤5 cm. Efforts should be made to evaluate tumor differentiation, and these results need to be confirmed prospectively in a larger population. Liver Transplantation 26 785-798 2020 AASLD. SEE EDITORIAL ON PAGE 748Intrahepatic cholangiocarcinoma (iCCA) accounts for 20%-25% of all cholangiocarcinoma (CCA) cases, and its incidence is rising at an average of 14% per year in Western countries. (1,2) Moreover, the mixed form of iCCA and hepatocellular carcinoma (HCC), referred to as combined hepatocellularcholangiocarcinoma (cHCC-CCA), is well recognized and increasingly reported. (3) Liver cirrhosis is a major risk factor for iCCA, with an odds ratio of 22.92 (95% confidence interval [CI], 18.24-28.79), De Martin et al. De Martin et al. liver transplantatiOn, June 2020

The Role of Surgical Resection and Liver Transplantation for the Treatment of Intrahepatic Cholangiocarcinoma

“…In an attempt to evaluate this size cut-off further, de Martin and colleagues retrospectively compared liver resection versus transplant for larger tumors. Patients with lesions 2–5 cm in diameter demonstrated a 5-year RFS of 74%, similar to those with smaller lesions, suggesting a 2-cm cut-off may be too conservative as a selection criterion, and that more patients may benefit from LT as a curative therapy for iCCA [ 117 ].…”

Should We Reevaluate Liver Transplantation as an Alternative to Resection for the Treatment of Intrahepatic Cholangiocarcinoma?

“…In this issue, De Martin et al present their multicenter study on this subject. ( 9 ) The study retrospectively evaluates patients undergoing LT (n = 49) compared to liver resection (LR, n = 26) identified as having iCCA and HCC‐CCA on explant pathology. The 1‐, 3‐, and 5‐year OS was similar at 90%, 76%, 67% for LT compared with 92%, 59%, and 40% for LR ( P = 0.17), with a trend toward improved longterm outcomes for the former.…”

“…Also, notably, differentiation rather than size correlated with tumor recurrence on multivariate analysis (hazard ratio, 6.66; P = 0.01). ( 9 )…”

“…Recurrence rates up to 79% have been reported following resection for iCCA, with tumor size, nodal status, presence of satellite lesions, and absence of adjuvant treatment being the strongest multivariate predictors of early recurrence. ( 10 ) Although LT appears to be equally, if not more, effective for lesions up to 5 cm, ( 6,7,9 ) one must justify the use of limited donor resources in the resectable patient, especially in the absence of underlying cirrhosis. Data from the present study suggest that LT is protective against recurrence, perhaps relating to improved oncologic margins and elimination of intrahepatic micrometastases.…”

Therapy of Primary Liver Cancer

“…The treatment options for cHCC-ICC are similar to those for HCC and ICC and include surgery, radiation, yttrium-90 radioembolization, chemotherapy, combined radiation and chemotherapy, combined surgery and chemotherapy, and triple therapy (surgery, radiation, and chemotherapy). 41 , 66 , 67 , 68 , 69 A recently retrospective analysis from 2001 to 2015 of 623 PLC patients, including 47 cHCC-ICC, 468 HCC, and 108 ICC patients, who underwent resection found that although cHCC-ICC is more poorly differentiated than HCC and ICC, it had a similar 5-year survival rate (49.7%, 54.8%, and 68.7%, respectively) and 3-year recurrence rate (57.9%, 61.5%, 56%, respectively). 70 …”