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

Alessandro Vitale(University of Padua), Pierluigi Romano(University of Padua), Umberto Cillo(University of Padua), Writing Group for the HE.RC.O.LE.S Collaborative Group(Collaborative Group (United States)), Writing Group for the ITA.LI.CA Collaborative Group(Collaborative Group (United States)), HE.RC.O.LE.S and ITA.LI.CA Collaborative Groups(Collaborative Group (United States)), Marco Busti(Collaborative Group (United States)), Giulia Nezi(Collaborative Group (United States)), Riccardo De Carlis(Collaborative Group (United States)), Francesca Ratti(Collaborative Group (United States)), Flavio Milana(Collaborative Group (United States)), Matteo Donadon(Collaborative Group (United States)), Laura Marinelli(Collaborative Group (United States)), Francesco Razionale(Collaborative Group (United States)), Francesca Carissimi(Collaborative Group (United States)), Mauro Alessandro Scotti(Collaborative Group (United States)), Cristina Ciuli(Collaborative Group (United States)), Valerio De Peppo(Collaborative Group (United States)), Nadia Russolillo(Collaborative Group (United States)), Mauro Giuffrida(Collaborative Group (United States)), Francesca De Stefano(Collaborative Group (United States)), Jacopo Peverada(Collaborative Group (United States)), Zoe Larghi Laureiro(Collaborative Group (United States)), Angelo Franceschi(Collaborative Group (United States)), Patrizia Pelizzo(Collaborative Group (United States)), Ivan Marchitelli(Collaborative Group (United States)), Annachiara Casella(Collaborative Group (United States)), Alberto Manzoni(Collaborative Group (United States)), Alessia Malagnino(Collaborative Group (United States)), Pietro Calcagno(Collaborative Group (United States)), Francesco Cammarata(Collaborative Group (United States)), Luca Pennacchi(Collaborative Group (United States)), Davide Cosola(Collaborative Group (United States)), Pio Corleone(Collaborative Group (United States)), Alessandro Cucchetti(Collaborative Group (United States)), G. Mantovani(Collaborative Group (United States)), Francesca Notte(Collaborative Group (United States)), Mauro Montuori(Collaborative Group (United States)), Gloria Allegrini(Collaborative Group (United States)), Calogero Cammà(Collaborative Group (United States)), Ciro Celsa(Collaborative Group (United States)), Paolo Giuffrida(Collaborative Group (United States)), Carmelo Marco Giacchetto(Collaborative Group (United States)), Gabriele Rancatore(Collaborative Group (United States)), Maria Vittoria Grassin(Collaborative Group (United States)), Roberta Ciccia(Collaborative Group (United States)), Alessandro Grova(Collaborative Group (United States)), M. Salvato(Collaborative Group (United States)), Elisabetta Biasini(Collaborative Group (United States)), Andrea Olivani(Collaborative Group (United States)), Rusi Chen(Collaborative Group (United States)), Alessandro Granito(Collaborative Group (United States)), Fabio Piscaglia(Collaborative Group (United States)), Bernardo Stefanini(Collaborative Group (United States)), Francesco Tovoli(Collaborative Group (United States)), Maurizio Biselli(Collaborative Group (United States)), Laura Bucci(Collaborative Group (United States)), Lorenzo Lani(Collaborative Group (United States)), Benedetta Stefanini(Collaborative Group (United States)), Vittoria Bevilacqua(Collaborative Group (United States)), Dante Berardinelli(Collaborative Group (United States)), Alberto Borghi(Collaborative Group (United States)), Andrea Casadei‐Gardini(Collaborative Group (United States)), Fabio Conti(Collaborative Group (United States)), A.C. Dall’Aglio(Collaborative Group (United States)), Giorgio Ercolan(Collaborative Group (United States)), Claudia Campani(Collaborative Group (United States)), Chiara Di Bonaventura(Collaborative Group (United States)), Stefano Gitto(Collaborative Group (United States)), Maria Stella Franzè(Collaborative Group (United States)), Assunta Sauchella(Collaborative Group (United States)), Pietro Coccoli(Collaborative Group (United States)), Antonio Malerba(Collaborative Group (United States)), Mario Capasso(Collaborative Group (United States)), Maria Guarino(Collaborative Group (United States)), Valentina Lauria(Collaborative Group (United States)), Giorgia Ghittoni(Collaborative Group (United States)), Giorgio Pelecca(Collaborative Group (United States)), Anna Sartori(Collaborative Group (United States)), A. Imondi(Collaborative Group (United States)), Barbara Penzo(Collaborative Group (United States)), Alessandro Inno(Collaborative Group (United States)), Fabiana Marchetti(Collaborative Group (United States)), Alessandro Di Menno di Bucchianico(Collaborative Group (United States)), Elton Dajti(Collaborative Group (United States)), Federico Ravaioli(Collaborative Group (United States)), Maria Corina Plaz Torres(Collaborative Group (United States)), Giulia Pieri(Collaborative Group (United States)), Filippo Olivieri(Collaborative Group (United States)), V. Romagnoli(Collaborative Group (United States)), Nicoletta De Matthaeis(Collaborative Group (United States)), Ester Marina(Collaborative Group (United States)), Antonio Facciorusso(Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico), Francesca Romana Ponziani(Collaborative Group (United States)), Andrea Lauterio(University of Parma), Angelo Sangiovanni(Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico), Giuseppe Cabibbo(Azienda USL di Bologna), Gabriele Missale(University of Parma), Mariarosaria Marseglia(Azienda USL di Bologna), Franco Trevisani(Humanitas University), Francesco Giuseppe Foschi(Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori), Federica Cipriani(University of Messina), Simone Famularo(Humanitas University), Fabio Marra(Azienda Ospedaliero Universitaria di Sassari), Carlo Saitta(University of Messina), Matteo Serenari(Azienda USL di Bologna), Gianpaolo Vidili(Ospedale di Bolzano), Filomena Morisco(University of Padua), Eugenio Caturelli(Marche Polytechnic University), Andrea Mega(Università Cattolica del Sacro Cuore), Filippo Pelizzaro(University of Padua), Daniele Nicolini(Marche Polytechnic University), Francesco Ardito(Università Cattolica del Sacro Cuore), Mattia Garancini(Azienda USL di Bologna), Alberto Masotto(Ospedale Sacro Cuore Don Calabria), Gianluca Svegliati‐Baroni(Marche Polytechnic University), Francesco Azzaroli(Azienda USL di Bologna), Edoardo G. Giannini(Ospedale Policlinico San Martino), Pasquale Perri(Istituti di Ricovero e Cura a Carattere Scientifico), Andrea Scarinci(University of Parma), Andrea Fontana(Azienda Ospedaliera Bolognini Seriate), Maurizia Rossana Brunetto(Azienda Ospedaliera Universitaria Pisana), Maurizio Iaria(University of Parma), Maria Di Marco(Policlinico Umberto I), Gerardo Nardone(Ospedale San Paolo), Tommaso Dominioni(University of Pavia), Quirino Lai(University of Foggia), Cecilia Ferrari(University of Padua), Gian Ludovico Rapaccini(University of Verona), Sacco Rodolfo(University of Foggia), Maurizio Romano(University of Padua), Simone Conci(University of Verona), Marco Zoli(Fondazione Poliambulanza Istituto Ospedaliero), Maria Conticchio(Aziende Socio Sanitarie Territoriali di Lecco), Matteo Zanello(Luigi Sacco Hospital), Giuseppe Zimmitti(University of Trieste), Luca Fumagalli(Università Cattolica del Sacro Cuore), Albert Troci(Luigi Sacco Hospital), Paola Germani(University of Trieste), Antonio Gasbarrini(Università Cattolica del Sacro Cuore), Giuliano La Barba(Ospedale G.B. Morgagni - L.Pierantoni), Michela De Angelis(Azienda Ospedaliera Carlo Poma), Stefan Patauner(Ospedale di Bolzano), Sarah Molfino(University of Padua), Mauro Zago(Aziende Socio Sanitarie Territoriali di Lecco), Enrico Pinotti(Ospedale di Bolzano), Anna Chiara Frigo(University of Padua), Gian Luca Baiocchi(Ospedale G.B. Morgagni - L.Pierantoni), Antonio Frena(University of Trieste), Luigi Boccia(Luigi Sacco Hospital), Giorgio Ercolani(Ospedale G.B. Morgagni - L.Pierantoni), Paola Tarchi(University of Trieste), Michele Crespi(Luigi Sacco Hospital), Marco Chiarelli(Aziende Socio Sanitarie Territoriali di Lecco), Moh’d Abu Hilal(University of Verona), Matteo Cescon(University of Padua), Riccardo Memeo(Ospedale San Paolo), Andrea Ruzzenente(University of Verona), Giacomo Zanus(University of Padua), Guido Griseri(University of Parma), Massimo Rossi(Policlinico Umberto I), Marcello Maestri(University of Pavia), Raffaele Della Valle(University of Parma), Alessandro Ferrero(Università Cattolica del Sacro Cuore), Gian Luca Grazi(Marche Polytechnic University), Fabrizio Romano(Azienda USL di Bologna), Felice Giuliante(Università Cattolica del Sacro Cuore), Marco Vivarelli(Marche Polytechnic University), Elio Jovine(Azienda USL di Bologna), Guido Torzilli(Humanitas University), Luca Aldrighetti(IRCCS Ospedale San Raffaele), Luciano De Carlis(University of Milano-Bicocca)
JAMA Surgery
May 15, 2024
Cited by 37Open Access
Full Text

Abstract

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.


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