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THE MANAGEMENT OF GALLBLADDER CANCER ACCORDING TO CONTEMPORARY SURGICAL ONCOLOGY PRINCIPLES WARRANTS SURVIVAL BENEFIT
Marcello Di Martino^*1, Benedetto Ielpo², Felice Giuliante³, John Martinie⁴, Guido Torzilli¹³, Luca Aldrighetti¹⁴, Francesco Izzo⁵, Michele Mazzola⁶, Oscar Guevara⁷, Hj Tan⁸, Iswanto Sucandy¹⁵, Francesco Lancellotti⁹, Aldo Rocca¹⁰, Pier Cristoforo Giulianotti¹¹, Luca Morelli¹², Matteo Donadon^1
1Universita degli Studi del Piemonte Orientale Amedeo Avogadro Scuola di Medicina, Novara, Piemonte, Italy; ²Hospital del Mar, Barcelona, Catalunya, Spain; ³Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Roma, Lazio, Italy; ⁴Carolinas Medical Center PinevilleCarolinas HealthCare System Pineville, Charlotte, NC; ⁵Istituto Nazionale Tumori IRCCS Fondazione Pascale, Napoli, Campania, Italy; ⁶ASST Grande Ospedale Metropolitano Niguarda De Gasperis Cardio Center, Milan, Lombardy, Italy; ⁷Instituto Nacional De Cancerología, Bogotá, Colombia, Bogotà, Colombia; ⁸Singapore General Hospital, Singapore, Singapore; ⁹Manchester Metropolitan University, Manchester, Manchester, United Kingdom; ¹⁰Pineta Grande Srl, Castel Volturno, Campania, Italy; ¹¹University of Illinois Chicago, Chicago, IL; ¹²Universita degli Studi di Pisa, Pisa, Toscana, Italy; ¹³Humanitas Mirasole Spa, Rozzano, Lombardia, Italy; ¹⁴IRCCS Ospedale San Raffaele, Milano, Italy; ¹⁵Tampa General Hospital, Tampa, FL

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 2012-2022. 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 CI95% 0.55-0.89) and overall survival (OS) (HR 0.68, p=0.002 CI95% 0.54-0.87) of pN0 but not in case of pN1. Patients receiving aCTx 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) compared to those with no-aCTx
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 more aggressive pathological factors, patients with adequate lymphadenectomy and aCTx with Capecitabine presented prolonged OS (15 vs 7.5 months, HR 0.52, p=0.029, 95%CI 0.28-0.93) 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.

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