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. 2025 Nov;51(11):110318.
doi: 10.1016/j.ejso.2025.110318. Epub 2025 Jul 29.

Adequate lymphadenectomy and adjuvant capecitabine warrant survival benefit in gallbladder cancer

M Di Martino  1 , B Ielpo  2 , S Cremona  2 , F Giuliante  3 , J Martinie  4 , A Ruzzenente  5 , G Torzilli  6 , L Aldrighetti  7 , F Izzo  8 , M Mazzola  9 , O Guevara  10 , H Tan  11 , I Sucandy  12 , F Lancellotti  13 , A Rocca  14 , P C Giulianotti  15 , L Morelli  16 , M Donadon  1 ; GBC Study Group
Collaborators, Affiliations
Free article

Adequate lymphadenectomy and adjuvant capecitabine warrant survival benefit in gallbladder cancer

M Di Martino et al. Eur J Surg Oncol. 2025 Nov.
Free article

Abstract

Background: Significant heterogeneity exists in the management of resectable gallbladder cancer (GBC), regarding the extent of lymphadenectomy and the role of adjuvant chemotherapy (aCTx). This study investigates outcomes of resected GBC according to contemporary surgical oncology principles.

Methods: The international database of the GBC Study Group was queried for patients with resected GBC between 2012 and 2022. Patients with ≥6 lymph nodes resected and aCTx were compared to those with inadequate lymphadenectomy or inadequate aCTX. Unadjusted and adjusted Cox regression models were employed to assess oncological outcomes.

Results: Out of 656 patients, 300 patients (45.7 %) had ≥6 lymph nodes resected, 240 (36.5 %) received any aCTx 323 and 118 (17.9 %) received capecitabine aCTx. Patients with adequate lymphadenectomy exhibited prolonged disease-free survival (DFS) (HR 0.69, p = 0.004 CI 95 % 0.55-0.89) and overall survival (OS) (HR 0.68, p = 0.002 CI 95 % 0.54-0.87) in pN0 but not in pN + cases. Patients receiving adjuvant capecitabine demonstrated prolonged DFS (HR 1.48, p < 0.001 95 %CI 1.20-1.83) and OS followed a similar pattern (HR 1.67, p < 0.001, 95 %CI 1.34-2.09). In the multivariable analysis, underlying hepatic disease (HR 2.75, p = 0.001, 95 %CI 1.49-5.07), adequate lymphadenectomy (HR 0.67, p = 0.020, 95 %CI 0.48-0.94), T stage (HR 2.14, p < 0.001, 95 %CI 1.60-2.86), R status (HR 1.88, p = 0.008, 95 %CI 1.18-3.00), and capecitabine aCTx (HR 1.27, p = 0.039 95 %CI 1.01-1.61) were identified as predictors of OS. Despite presenting with more aggressive disease, patients with adequate lymphadenectomy and aCTx with capecitabine presented prolonged OS (15 vs 7.5 months, HR 0.53, p = 0.038, 95 %CI 0.29-0.96) compared to those without lymphadenectomy or aCTx.

Conclusions: A significant proportion of patients still did not receive adequate lymphadenectomy and aCTx. Patients treated according to contemporary surgical oncology principles presented a survival benefit. These principles should be further evaluated considering the aggressiveness of GBC.

Keywords: Adjuvant chemotherapy; Biliary tract cancer; Capecitabine; Gabblader cancer; Liver resection; Lymphadenectomy; Surgical oncology.

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Conflict of interest statement

Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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