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Comparative Study
. 2024 Aug 1;159(8):881-889.
doi: 10.1001/jamasurg.2024.1184.

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

Alessandro Vitale  1 , Pierluigi Romano  1 , Umberto Cillo  1 ; 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; 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 , 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 , Luciano De Carlis  2
Collaborators, Affiliations
Comparative Study

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

Alessandro Vitale et al. JAMA Surg. .

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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Conflict of interest statement

Conflict of Interest Disclosures: Dr Trevisani reported grants from AstraZeneca, AbbVie, Bayer, MSD, and Roche and personal fees from EISAI during the conduct of the study. Dr Marra reported personal fees from AstraZeneca, MSD/EISAI, Ipsen, and Roche; nonfinancial support from AlfaSigma and Gilead outside the submitted work. Dr Pelizzaro reported grants from MSD and EISAI outside the submitted work. Dr Brunetto reported advisory or speakers’ bureau fees from Roche and AstraZeneca during the conduct of the study and from Gilead outside the submitted work. Dr Baiocchi reported personal fees from Stryker outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Probability of Overall Survival in the Unweighted Populations of the Liver Resection (LR), Percutaneous Radiofrequency Ablation (PRFA), and Transarterial Chemoembolization (TACE) Groups
Figure 2.
Figure 2.. Probability of Overall Survival in the Liver Resection (LR), Percutaneous Radiofrequency Ablation (PRFA), and Transarterial Chemoembolization (TACE) Populations After Matching-Adjusted Indirect Comparison Adjustment
See this image and copyright information in PMC

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