Liver Resection vs Nonsurgical Treatments for Patients With Early Multinodular Hepatocellular Carcinoma

Alessandro Vitale, 1; Pierluigi Romano, 1; Umberto Cillo, 1; S Collaborative Group, Writing Group for the HE. RC. O. LE.; CA Collaborative Group, Writing Group for the ITA. LI.; CA Collaborative Groups, HE. RC. O. LE. S. and ITA. LI.; Andrea Lauterio, 2; Angelo Sangiovanni, 3; Giuseppe Cabibbo, 4; Gabriele Missale, 5; Mariarosaria Marseglia, 6; Franco Trevisani, 7; Francesco Giuseppe Foschi, 8; Federica Cipriani, 9; Cipriani, Federica; Simone Famularo 10,; Fabio Marra 11,; Carlo Saitta 12,; Matteo Serenari 13,; Gianpaolo Vidili 14,; Filomena Morisco 15,; Eugenio Caturelli 16,; Andrea Mega 17,; Filippo Pelizzaro 18,; Daniele Nicolini 19,; Francesco Ardito 20,; Mattia Garancini 21,; Alberto Masotto 22,; Gianluca Svegliati Baroni 23,; Francesco Azzaroli 24,; Edoardo Giannini 25 26,; Pasquale Perri 27,; Andrea Scarinci 27,; Andrea Pierluigi Fontana 28,; Maurizia Rossana Brunetto 29,; Maurizio Iaria 30,; Maria Di Marco 31,; Gerardo Nardone 32,; Tommaso Dominioni 33,; Quirino Lai 34,; Cecilia Ferrari 35,; Gian Ludovico Rapaccini 36,; Sacco Rodolfo 37,; Maurizio Romano 38,; Simone Conci 39,; Marco Zoli 40,; Maria Conticchio 41,; Matteo Zanello 42,; Giuseppe Zimmitti 43,; Luca Fumagalli 44,; Albert Troci 45,; Paola Germani 46,; Antonio Gasbarrini 47,; Giuliano La Barba 48,; Michela De Angelis 49,; Stefan Patauner 50,; Sarah Molfino 51,; Mauro Zago 52,; Enrico Pinotti 52,; Anna Chiara Frigo 53,; Gian Luca Baiocchi 51,; Antonio Frena 50,; Luigi Boccia 49,; Giorgio Ercolani 48,; Paola Tarchi 46,; Michele Crespi 45,; Marco Chiarelli 44,; Moh'd Abu Hilal 43,; Matteo Cescon 42,; Riccardo Memeo 41,; Andrea Ruzzenente 39,; Giacomo Zanus 38,; Guido Griseri 35,; Massimo Rossi 34,; Marcello Maestri 33,; Raffaele Della Valle 30,; Alessandro Ferrero 28,; Gian Luca Grazi 27 54,; Fabrizio Romano 21,; Felice Giuliante 20,; Marco Vivarelli 19,; Elio Jovine 13,; Guido Torzilli 10,; Luca Aldrighetti, 9; Aldrighetti, Luca; Luciano De Carlis, 2

doi:10.1001/jamasurg.2024.1184

Importance The 2022 Barcelona Clinic Liver Cancer algorithm currently discourages liver resection (LR) for patients with multinodular hepatocellular carcinoma (HCC) presenting with 2 or 3 nodules that are each 3 cm or smaller. Objective To compare the efficacy of liver resection (LR), percutaneous radiofrequency ablation (PRFA), and transarterial chemoembolization (TACE) in patients with multinodular HCC. Design, Setting, and Participants This cohort study is a retrospective analysis conducted using data from the HE.RC.O.LE.S register (n = 5331) for LR patients and the ITA.LI.CA database (n = 7056) for PRFA and TACE patients. A matching-adjusted indirect comparison (MAIC) method was applied to balance data and potential confounding factors between the 3 groups. Included were patients from multiple centers from 2008 to 2020; data were analyzed from January to December 2023. Interventions LR, PRFA, or TACE. Main Outcomes and Measures Survival rates at 1, 3, and 5 years were calculated. Cox MAIC-weighted multivariable analysis and competing risk analysis were used to assess outcomes. Results A total of 720 patients with early multinodular HCC were included, 543 males (75.4%), 177 females (24.6%), and 350 individuals older than 70 years (48.6%). There were 296 patients in the LR group, 240 who underwent PRFA, and 184 who underwent TACE. After MAIC, LR exhibited 1-, 3-, and 5-year survival rates of 89.11%, 70.98%, and 56.44%, respectively. PRFA showed rates of 94.01%, 65.20%, and 39.93%, while TACE displayed rates of 90.88%, 48.95%, and 29.24%. Multivariable Cox survival analysis in the weighted population showed a survival benefit over alternative treatments (PRFA vs LR: hazard ratio [HR], 1.41; 95% CI, 1.07-1.86; P = .01; TACE vs LR: HR, 1.86; 95% CI, 1.29-2.68; P = .001). Competing risk analysis confirmed a lower risk of cancer-related death in LR compared with PRFA and TACE. Conclusions and Relevance For patients with early multinodular HCC who are ineligible for transplant, LR should be prioritized as the primary therapeutic option, followed by PRFA and TACE when LR is not feasible. These findings provide valuable insights for clinical decision-making in this patient population.

Liver Resection vs Nonsurgical Treatments for Patients With Early Multinodular Hepatocellular Carcinoma / 1, Alessandro Vitale; 1, Pierluigi Romano; 1, Umberto Cillo; S Collaborative Group, Writing Group for the HE. RC. O. LE.; CA Collaborative Group, Writing Group for the ITA. LI.; CA Collaborative Groups, HE. RC. O. LE. S. and ITA. LI.; 2, Andrea Lauterio; 3, Angelo Sangiovanni; 4, Giuseppe Cabibbo; 5, Gabriele Missale; 6, Mariarosaria Marseglia; 7, Franco Trevisani; 8, Francesco Giuseppe Foschi; 9, Federica Cipriani; Cipriani, Federica; Famularo 10, Simone; Marra 11, Fabio; Saitta 12, Carlo; Serenari 13, Matteo; Vidili 14, Gianpaolo; Morisco 15, Filomena; Caturelli 16, Eugenio; Mega 17, Andrea; Pelizzaro 18, Filippo; Nicolini 19, Daniele; Ardito 20, Francesco; Garancini 21, Mattia; Masotto 22, Alberto; Svegliati Baroni 23, Gianluca; Azzaroli 24, Francesco; Giannini 25 26, Edoardo; Perri 27, Pasquale; Scarinci 27, Andrea; Pierluigi Fontana 28, Andrea; Rossana Brunetto 29, Maurizia; Iaria 30, Maurizio; Di Marco 31, Maria; Nardone 32, Gerardo; Dominioni 33, Tommaso; Lai 34, Quirino; Ferrari 35, Cecilia; Ludovico Rapaccini 36, Gian; Rodolfo 37, Sacco; Romano 38, Maurizio; Conci 39, Simone; Zoli 40, Marco; Conticchio 41, Maria; Zanello 42, Matteo; Zimmitti 43, Giuseppe; Fumagalli 44, Luca; Troci 45, Albert; Germani 46, Paola; Gasbarrini 47, Antonio; La Barba 48, Giuliano; De Angelis 49, Michela; Patauner 50, Stefan; Molfino 51, Sarah; Zago 52, Mauro; Pinotti 52, Enrico; Chiara Frigo 53, Anna; Luca Baiocchi 51, Gian; Frena 50, Antonio; Boccia 49, Luigi; Ercolani 48, Giorgio; Tarchi 46, Paola; Crespi 45, Michele; Chiarelli 44, Marco; Abu Hilal 43, Moh'D; Cescon 42, Matteo; Memeo 41, Riccardo; Ruzzenente 39, Andrea; Zanus 38, Giacomo; Griseri 35, Guido; Rossi 34, Massimo; Maestri 33, Marcello; Della Valle 30, Raffaele; Ferrero 28, Alessandro; Luca Grazi 27 54, Gian; Romano 21, Fabrizio; Giuliante 20, Felice; Vivarelli 19, Marco; Jovine 13, Elio; Torzilli 10, Guido; 9, Luca Aldrighetti; Aldrighetti, Luca; 2, Luciano De Carlis. - In: JAMA SURGERY. - ISSN 2168-6254. - (2024). [10.1001/jamasurg.2024.1184]