Liver Resection vs Nonsurgical Treatments for Patients With Early Multinodular Hepatocellular Carcinoma
Authors: Vitale Alessandro , Romano Pierluigi , Cillo Umberto ,   Writing Group for the HE.RC.O.LE.S Collaborative Group,   Writing Group for the ITA.LI.CA Collaborative Group,   HE.RC.O.LE.S and ITA.LI.CA Collaborative Groups, Busti Marco , Nezi Giulia , De Carlis Riccardo , Ratti Francesca , Milana Flavio , Donadon Matteo , Marinelli Laura , Razionale Francesco , Carissimi Francesca , Scotti Mauro Alessandro , Ciuli Cristina , De Peppo Valerio , Russolillo Nadia , Giuffrida Mauro , De Stefano Francesca , Peverada Jacopo , Larghi Laureiro Zoe , Franceschi Angelo , Pelizzo Patrizia , Marchitelli Ivan , Casella Annachiara , Manzoni Alberto , Malagnino Alessia , Calcagno Pietro , Cammarata Francesco , Pennacchi Luca , Cosola Davide , Corleone Pio , Cucchetti Alessandro , Mantovani Guido , Notte Francesca , Montuori Mauro , Allegrini Gloria , Cammà Calogero , Celsa Ciro , Giuffrida Paolo , Giacchetto Carmelo Marco , Rancatore Gabriele , Grassin Maria Vittoria , Ciccia Roberta , Grova Alessandro , Salvato Mauro , Biasini Elisabetta , Olivani Andrea , Chen Rusi , Granito Alessandro , Piscaglia Fabio , Stefanini Bernardo , Tovoli Francesco , Biselli Maurizio , Bucci Laura , Lani Lorenzo , Stefanini Benedetta , Bevilacqua Vittoria , Berardinelli Dante , Borghi Alberto , Casadei Gardini Andrea , Conti Fabio , Dall'Aglio Anna Chiara , Ercolan Giorgio , Campani Claudia , Di Bonaventura Chiara , Gitto Stefano , Franzè Maria Stella , Sauchella Assunta , Coccoli Pietro , Malerba Antonio , Capasso Mario , Guarino Maria , Lauria Valentina , Ghittoni Giorgia , Pelecca Giorgio , Sartori Anna , Imondi Angela , Penzo Barbara , Inno Alessandro , Marchetti Fabiana , Di Bucchianico Alessandro , Dajti Elton , Ravaioli Federico , Plaz Torres Maria Corina , Pieri Giulia , Olivieri Filippo , Romagnoli Veronica , de Matthaeis Nicoletta , Cela Ester Marina , Facciorusso Antonio , Ponziani Francesca Romana , Lauterio Andrea , Sangiovanni Angelo , Cabibbo Giuseppe , Missale Gabriele , Marseglia Mariarosaria , Trevisani Franco , Foschi Francesco Giuseppe , Cipriani Federica , Famularo Simone , Marra Fabio , Saitta Carlo , Serenari Matteo , Vidili Gianpaolo , Morisco Filomena , Caturelli Eugenio , Mega Andrea , Pelizzaro Filippo , Nicolini Daniele , Ardito Francesco , Garancini Mattia , Masotto Alberto , Baroni Gianluca Svegliati , Azzaroli Francesco , Giannini Edoardo , Perri Pasquale , Scarinci Andrea , Fontana Andrea Pierluigi , Brunetto Maurizia Rossana , Iaria Maurizio , Di Marco Maria , Nardone Gerardo , Dominioni Tommaso , Lai Quirino , Ferrari Cecilia , Rapaccini Gian Ludovico , Rodolfo Sacco , Romano Maurizio , Conci Simone , Zoli Marco , Conticchio Maria , Zanello Matteo , Zimmitti Giuseppe , Fumagalli Luca , Troci Albert , Germani Paola , Gasbarrini Antonio , La Barba Giuliano , De Angelis Michela , Patauner Stefan , Molfino Sarah , Zago Mauro , Pinotti Enrico , Frigo Anna Chiara , Baiocchi Gian Luca , Frena Antonio , Boccia Luigi , Ercolani Giorgio , Tarchi Paola , Crespi Michele , Chiarelli Marco , Abu Hilal Moh’d , Cescon Matteo , Memeo Riccardo , Ruzzenente Andrea , Zanus Giacomo , Griseri Guido , Rossi Massimo , Maestri Marcello , Della Valle Raffaele , Ferrero Alessandro , Grazi Gian Luca , Romano Fabrizio , Giuliante Felice , Vivarelli Marco , Jovine Elio , Torzilli Guido , Aldrighetti Luca , De Carlis Luciano 
Published: May 2024

ImportanceThe 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.ObjectiveTo compare the efficacy of liver resection (LR), percutaneous radiofrequency ablation (PRFA), and transarterial chemoembolization (TACE) in patients with multinodular HCC.Design, Setting, and ParticipantsThis 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.InterventionsLR, PRFA, or TACE.Main Outcomes and MeasuresSurvival rates at 1, 3, and 5 years were calculated. Cox MAIC-weighted multivariable analysis and competing risk analysis were used to assess outcomes.ResultsA 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 RelevanceFor 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.