JHEP Reports (Aug 2025)
Minimally invasive hepatectomy vs. thermoablation for single small (≤3 cm) hepatocellular carcinoma: A weighted real-life national comparison
- Felice Giuliante,
- Simone Famularo,
- Sara Grasselli,
- Angelo Sangiovanni,
- Alessandro Vitale,
- Giuseppe Cabibbo,
- Andrea Lauterio,
- Federica Cipriani,
- Alice Saccomandi,
- Marco Arru,
- Elisa Pinto,
- Maurizia Rossana Brunetto,
- Maria Stella Franzè,
- Camilla Graziosi,
- Claudia Campani,
- Fabio Marra,
- Mariella Di Marco,
- Mariarosaria Marseglia,
- Valentina Santi,
- Mario Capasso,
- Alberto Masotto,
- Andrea Fontana,
- Maurizio Iaria,
- Alba Rocco,
- Matteo Serenari,
- Andrea Mega,
- Antonio Gasbarrini,
- Maria Corina Plaz Torres,
- Mattia Garancini,
- Simone Conci,
- Elton Dajti,
- Pasquale Perri,
- Rodolfo Sacco,
- Mariano Giglio,
- Cecilia Ferari,
- Michela De Angelis,
- Albert Troci,
- Donatella Magalotti,
- Daniele Nicolini,
- Giuseppe Zimmitti,
- Paola Germani,
- Laura Schiadà,
- Maria Conticchio,
- Matteo Zanello,
- Maurizio Romano,
- Flavio Milana,
- Quirino Lai,
- Stefan Patauner,
- Antonio Frena,
- Massimo Rossi,
- Guido Torzilli,
- Giacomo Zanus,
- Elio Jovine,
- Riccardo Memeo,
- Gianluca Svegliati-Baroni,
- Paola Tarchi,
- Moh’d Abu Hilal,
- Marco Vivarelli,
- Michele Crespi,
- Luigi Boccia,
- Guido Griseri,
- Roberto Ivan Troisi,
- Gian Luca Grazi,
- Francesco Azzaroli,
- Andrea Ruzzenente,
- Fabrizio Romano,
- Edoardo G. Giannini,
- Matteo Cescon,
- Gerardo Nardone,
- Raffaele Dalla Valle,
- Alessandro Ferrero,
- Filomena Morisco,
- Fabio Piscaglia,
- Giorgia Ghittoni,
- Carlo Saitta,
- Filippo Pelizzaro,
- Gianpaolo Vidili,
- Francesco Giuseppe Foschi,
- Luca Aldrighetti,
- Luciano De Carlis,
- Umberto Cillo,
- Elisabetta Biasini,
- Davide Bernasconi,
- Francesco Ardito,
- Franco Trevisani,
- Francesco Razionale,
- Gabriele Missale,
- Andrea Olivani,
- Gloria Allegrini,
- Pierluigi Romano,
- Calogero Cammà,
- Ciro Celsa,
- Paolo Giuffrida,
- Carmelo Marco Giacchetto,
- Gabriele Rancatore,
- Maria Vittoria Grassini,
- Roberta Ciccia,
- Alessandro Grova,
- Mauro Salvato,
- Riccardo De Carlis,
- Francesca Ratti,
- Lucia Napoli,
- Alberto Borghi,
- Fabio Conti,
- Luca Ielasi,
- Marco Ferronato,
- Nicola Reggidori,
- Fabio Farinati,
- Federica Bertellini,
- Giorgio Palano,
- Maria Piera Kitenge,
- Filippo Oliveri,
- Gabriele Ricco,
- Veronica Romagnoli,
- Roberto Filomia,
- Concetta Pitrone,
- Giovanni Raimondo,
- Valentina Lauria,
- Giorgio Pelecca,
- Tancredi Li Cavoli,
- Lucia Ragozzino,
- Stefano Gitto,
- Martina Rosi,
- Valentina Adotti,
- Alessandro Granito,
- Francesco Tovoli,
- Bernardo Stefanini,
- Maurizio Biselli,
- Lorenzo Lani,
- Benedetta Stefanini,
- Maria Guarino,
- Valentina Cossiga,
- Alessandro Inno,
- Fabiana Marchetti,
- Nadia Russolillo,
- Mario Giuffrida,
- Pietro Coccoli,
- Alba Rocco,
- Luca Marzi,
- Nicoletta de Matthaeis,
- Francesca Romana Ponziani,
- Andrea Pasta,
- Giulia Pieri,
- Cristina Ciulli,
- Mauro Scotti,
- Ivan Marchitelli,
- Alberto Porro,
- Valerio De Peppo,
- Ester Marina Cela,
- Antonio Facciorusso,
- Renato Patrone,
- Angelo Franceschi,
- Laura Marinelli,
- Davide Cosola,
- Chiara Scorzoni,
- Giulia Scandali,
- Annachiara Casella,
- Patrizia Pelizzo,
- Fabio Procopio,
- Zoe Larghi Laurerio,
- Francesca Notte
Affiliations
- Felice Giuliante
- Hepatobiliary Surgery Unit, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Catholic University of the Sacred Heart, Rome, Italy; Corresponding author. Address: Hepatobiliary and General Surgery Unit, Foundation University Hospital “A. Gemelli” IRCCS, Sacred Heart Catholic University, Viale Agostino Gemelli 8, 00136 Rome, Italy.
- Simone Famularo
- Hepatobiliary Surgery Unit, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Catholic University of the Sacred Heart, Rome, Italy; IRCAD, Research Institute Against Cancer of the Digestive System, Strasbourg, France
- Sara Grasselli
- Department of Medicine and Surgery, Infectious Diseases and Hepatology Unit, University of Parma and Azienda Ospedaliero-Universitaria of Parma, Parma, Italy
- Angelo Sangiovanni
- Division of Gastroenterology and Hepatology, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico and C.R.C. “A.M. & A. Migliavacca Center for Liver Disease”, Milan, Italy
- Alessandro Vitale
- Department of Surgical, Oncological and Gastroenterological Sciences (DiSCOG), University of Padova, Second General Surgical Unit, Padova Teaching Hospital, Padua, Italy
- Giuseppe Cabibbo
- Section of Gastroenterology and Hepatology, Department of Health Promotion, Mother & Child Care, Internal Medicine & Medical Specialties (PROMISE), Gastroenterology & Hepatology Unit, University of Palermo, Palermo, Italy
- Andrea Lauterio
- General Surgery and Abdominal Organ Transplantation, ASST Grande Ospedale Metropolitano Milano Niguarda; School of Medicine and Surgery, University of Milan-Bicocca, Milan, Italy
- Federica Cipriani
- Hepatobiliary Surgery Division, “Vita e Salute” University, Ospedale San Raffaele IRCCS, Milan, Italy
- Alice Saccomandi
- Department of Internal Medicine, Ospedale per gli Infermi di Faenza, Faenza, Italy
- Marco Arru
- Department of Medicine, Surgery and Pharmacy. Azienda Ospedaliero-Universitaria of Sassari, Sassari, Italy
- Elisa Pinto
- Department of Surgery, Oncology and Gastroenterology, Gastroenterology Unit, University of Padua, Padua, Italy
- Maurizia Rossana Brunetto
- Department of Clinical and Experimental Medicine, Hepatology and Liver Physiopathology Laboratory, University Hospital of Pisa, Pisa, Italy
- Maria Stella Franzè
- Department of Clinical and Experimental Medicine, Clinical and Molecular Hepatology Unit, University of Messina, Messina, Italy
- Camilla Graziosi
- Gastroenterology Unit, Belcolle Hospital, Viterbo, Italy
- Claudia Campani
- Department of Experimental and Clinical Medicine, Internal Medicine and Hepatology Unit, University of Florence, Florence, Italy
- Fabio Marra
- Department of Experimental and Clinical Medicine, Internal Medicine and Hepatology Unit, University of Florence, Florence, Italy
- Mariella Di Marco
- Medicine Unit, Bolognini Hospital, Seriate, Italy
- Mariarosaria Marseglia
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
- Valentina Santi
- Unit of Semeiotics, Liver and Alcohol Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
- Mario Capasso
- Department of Clinical Medicine and Surgery, Diseases of the Liver and Biliary System Unit, University of Naples ''Federico II'', Naples, Italy
- Alberto Masotto
- Gastroenterology Unit, IRCCS Sacro Cuore Don Calabria Hospital, Negrar, Italy
- Andrea Fontana
- Department of General and Oncological Surgery, Mauriziano Hospital ''Umberto I'', Turin, Italy
- Maurizio Iaria
- Department of General and Specialized Surgery, Division of General Surgery, Parma University Hospital, Parma, Italy
- Alba Rocco
- Department of Clinical Medicine and Surgery, Hepato-Gastroenterology Unit, University of Naples ''Federico II'', Naples, Italy
- Matteo Serenari
- Hepato-biliary Surgery and Transplant Unit, Policlinico Sant'Orsola IRCCS, Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
- Andrea Mega
- Gastroenterology Unit, Bolzano Regional Hospital, Bolzano, Italy
- Antonio Gasbarrini
- Liver Unit, CEMAD – Centro Malattie Dell’Apparato Digerente, Medicina Interna e Gastroenterologia, Università Cattolica Del Sacro Cuore, Fondazione Policlinico Universitario Gemelli IRCCS, Rome, Italy
- Maria Corina Plaz Torres
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, Genoa, Italy; IRCCS Ospedale Policlinico San Martino, Genoa, Italy
- Mattia Garancini
- School of Medicine and Surgery, University of Milano-Bicocca; IRCCS San Gerardo Dei Tintori Hospital, Monza, Italy
- Simone Conci
- Division of General and Hepatobiliary Surgery, Department of Surgical Sciences, Dentistry, Gynecology and Pediatrics, University of Verona, Verona, Italy
- Elton Dajti
- Division of Gastroenterology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
- Pasquale Perri
- Division of Hepatobiliarypancreatic Unit, IRCCS - Regina Elena National Cancer Institute, Rome, Italy
- Rodolfo Sacco
- Gastroenterology and Digestive Endoscopy Unit, Foggia University Hospital, Foggia, Italy
- Mariano Giglio
- Division of Hepato-biliary-pancreatic, Minimally Invasive and Robotic Surgery, and Transplantation Service Federico II University Hospital, Naples, Italy
- Cecilia Ferari
- HPB Surgical Unit, San Paolo Hospital, Savona, Italy
- Michela De Angelis
- Department of General Surgery, Ospedale Carlo Poma, Mantua, Italy
- Albert Troci
- Department of Surgery, L. Sacco Hospital, Milan, Italy
- Donatella Magalotti
- Division of Internal Medicine, Neurovascular and Hepatometabolic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
- Daniele Nicolini
- HPB Surgery and Transplantation Unit, Department of Clinical and Experimental Medicine, Polytechnic University of Marche, Ancona, Italy
- Giuseppe Zimmitti
- Department of General Surgery, Poliambulanza Foundation Hospital, Brescia, Italy
- Paola Germani
- Division of General Surgery, Department of Medical and Surgical Sciences, ASUGI, Trieste, Italy
- Laura Schiadà
- Liver Injury and Transplant Unit, Polytechnic University of Marche, Ancona, Italy
- Maria Conticchio
- Department of Hepato-Pancreatc-Biliary Surgery, “F. Miulli” General Regional Hospital, Acquaviva Delle Fonti, Bari, Italy; Department of Medicine and Surgery, LUM University, Casamassima, Bari, Italy
- Matteo Zanello
- Alma Mater Studiorum, University of Bologna, AOU Sant'Orsola Malpighi, IRCCS at Maggiore Hospital, Bologna, Italy
- Maurizio Romano
- Department of Surgical, Oncological and Gastroenterological Science (DISCOG), University of Padua, Hepatobiliary and Pancreatic Surgery Unit - Treviso Hospital, Italy
- Flavio Milana
- Department of Hepatobiliary and General Surgery, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
- Quirino Lai
- General Surgery and Organ Transplantation Unit, Sapienza University of Rome, Umberto I Polyclinic of Rome, Rome, Italy
- Stefan Patauner
- Department of General and Pediatric Surgery, Bolzano Central Hospital, Bolzano, Italy
- Antonio Frena
- Department of General and Pediatric Surgery, Bolzano Central Hospital, Bolzano, Italy
- Massimo Rossi
- General Surgery and Organ Transplantation Unit, Sapienza University of Rome, Umberto I Polyclinic of Rome, Rome, Italy
- Guido Torzilli
- Department of Hepatobiliary and General Surgery, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
- Giacomo Zanus
- Department of Surgical, Oncological and Gastroenterological Science (DISCOG), University of Padua, Hepatobiliary and Pancreatic Surgery Unit - Treviso Hospital, Italy
- Elio Jovine
- Hepato-biliary Surgery and Transplant Unit, Policlinico Sant'Orsola IRCCS, Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
- Riccardo Memeo
- Department of Hepato-Pancreatc-Biliary Surgery, “F. Miulli” General Regional Hospital, Acquaviva Delle Fonti, Bari, Italy; Department of Medicine and Surgery, LUM University, Casamassima, Bari, Italy
- Gianluca Svegliati-Baroni
- Liver Injury and Transplant Unit, Polytechnic University of Marche, Ancona, Italy
- Paola Tarchi
- Division of General Surgery, Department of Medical and Surgical Sciences, ASUGI, Trieste, Italy
- Moh’d Abu Hilal
- Department of General Surgery, Poliambulanza Foundation Hospital, Brescia, Italy
- Marco Vivarelli
- HPB Surgery and Transplantation Unit, Department of Clinical and Experimental Medicine, Polytechnic University of Marche, Ancona, Italy
- Michele Crespi
- Department of Surgery, L. Sacco Hospital, Milan, Italy
- Luigi Boccia
- Department of General Surgery, Ospedale Carlo Poma, Mantua, Italy
- Guido Griseri
- HPB Surgical Unit, San Paolo Hospital, Savona, Italy
- Roberto Ivan Troisi
- Division of Hepato-biliary-pancreatic, Minimally Invasive and Robotic Surgery, and Transplantation Service Federico II University Hospital, Naples, Italy
- Gian Luca Grazi
- HepatoBiliaryPancreatic Unit - AOU Careggi - University of Florence, Florence, Italy
- Francesco Azzaroli
- Division of Gastroenterology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
- Andrea Ruzzenente
- Division of General and Hepatobiliary Surgery, Department of Surgical Sciences, Dentistry, Gynecology and Pediatrics, University of Verona, Verona, Italy
- Fabrizio Romano
- School of Medicine and Surgery, University of Milano-Bicocca; IRCCS San Gerardo Dei Tintori Hospital, Monza, Italy
- Edoardo G. Giannini
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, Genoa, Italy; IRCCS Ospedale Policlinico San Martino, Genoa, Italy
- Matteo Cescon
- Hepato-biliary Surgery and Transplant Unit, Policlinico Sant'Orsola IRCCS, Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
- Gerardo Nardone
- Department of Clinical Medicine and Surgery, Hepato-Gastroenterology Unit, University of Naples ''Federico II'', Naples, Italy
- Raffaele Dalla Valle
- Department of General and Specialized Surgery, Division of General Surgery, Parma University Hospital, Parma, Italy
- Alessandro Ferrero
- Department of General and Oncological Surgery, Mauriziano Hospital ''Umberto I'', Turin, Italy
- Filomena Morisco
- Department of Clinical Medicine and Surgery, Diseases of the Liver and Biliary System Unit, University of Naples ''Federico II'', Naples, Italy
- Fabio Piscaglia
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
- Giorgia Ghittoni
- Gastroenterology Unit, Belcolle Hospital, Viterbo, Italy
- Carlo Saitta
- Department of Clinical and Experimental Medicine, Clinical and Molecular Hepatology Unit, University of Messina, Messina, Italy
- Filippo Pelizzaro
- Department of Surgery, Oncology and Gastroenterology, Gastroenterology Unit, University of Padua, Padua, Italy
- Gianpaolo Vidili
- Department of Medicine, Surgery and Pharmacy. Azienda Ospedaliero-Universitaria of Sassari, Sassari, Italy
- Francesco Giuseppe Foschi
- Department of Internal Medicine, Ospedale per gli Infermi di Faenza, Faenza, Italy
- Luca Aldrighetti
- Hepatobiliary Surgery Division, “Vita e Salute” University, Ospedale San Raffaele IRCCS, Milan, Italy
- Luciano De Carlis
- General Surgery and Abdominal Organ Transplantation, ASST Grande Ospedale Metropolitano Milano Niguarda; School of Medicine and Surgery, University of Milan-Bicocca, Milan, Italy
- Umberto Cillo
- Department of Surgical, Oncological and Gastroenterological Sciences (DiSCOG), University of Padova, Second General Surgical Unit, Padova Teaching Hospital, Padua, Italy
- Elisabetta Biasini
- Department of Medicine and Surgery, Infectious Diseases and Hepatology Unit, University of Parma and Azienda Ospedaliero-Universitaria of Parma, Parma, Italy
- Davide Bernasconi
- Center of Biostatistics for Clinical Epidemiology, School of Medicine and Surgery, University of Milan - Bicocca, Monza, Italy
- Francesco Ardito
- Hepatobiliary Surgery Unit, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Catholic University of the Sacred Heart, Rome, Italy
- Franco Trevisani
- Unit of Semeiotics, Liver and Alcohol Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
- Francesco Razionale
- Gabriele Missale
- Andrea Olivani
- Gloria Allegrini
- Pierluigi Romano
- Calogero Cammà
- Ciro Celsa
- Paolo Giuffrida
- Carmelo Marco Giacchetto
- Gabriele Rancatore
- Maria Vittoria Grassini
- Roberta Ciccia
- Alessandro Grova
- Mauro Salvato
- Riccardo De Carlis
- Francesca Ratti
- Lucia Napoli
- Alberto Borghi
- Fabio Conti
- Luca Ielasi
- Marco Ferronato
- Nicola Reggidori
- Fabio Farinati
- Federica Bertellini
- Giorgio Palano
- Maria Piera Kitenge
- Filippo Oliveri
- Gabriele Ricco
- Veronica Romagnoli
- Roberto Filomia
- Concetta Pitrone
- Giovanni Raimondo
- Valentina Lauria
- Giorgio Pelecca
- Tancredi Li Cavoli
- Lucia Ragozzino
- Stefano Gitto
- Martina Rosi
- Valentina Adotti
- Alessandro Granito
- Francesco Tovoli
- Bernardo Stefanini
- Maurizio Biselli
- Lorenzo Lani
- Benedetta Stefanini
- Maria Guarino
- Valentina Cossiga
- Alessandro Inno
- Fabiana Marchetti
- Nadia Russolillo
- Mario Giuffrida
- Pietro Coccoli
- Alba Rocco
- Luca Marzi
- Nicoletta de Matthaeis
- Francesca Romana Ponziani
- Andrea Pasta
- Giulia Pieri
- Cristina Ciulli
- Mauro Scotti
- Ivan Marchitelli
- Alberto Porro
- Valerio De Peppo
- Ester Marina Cela
- Antonio Facciorusso
- Renato Patrone
- Angelo Franceschi
- Laura Marinelli
- Davide Cosola
- Chiara Scorzoni
- Giulia Scandali
- Annachiara Casella
- Patrizia Pelizzo
- Fabio Procopio
- Zoe Larghi Laurerio
- Francesca Notte
- DOI
- https://doi.org/10.1016/j.jhepr.2025.101420
- Journal volume & issue
-
Vol. 7,
no. 8
p. 101420
Abstract
Background & Aims: For patients with single small (≤3 cm) hepatocellular carcinoma ablation is the first-line treatment, although a high rate of recurrence has been reported. The aim was to compare videolaparoscopic liver resection (laparoscopic resection group) vs. percutaneous thermoablation (ablation group) in terms of overall survival, recurrence-free survival and early recurrence in a real-life national scenario. Methods: The study is a retrospective collection with subsequent survival analysis. Data were collected from two Italian HCC registries, ITA.LI.CA and HE.RC.O.LE.S. An inverse probability of treatment weighting analysis was performed to balance baseline differences between groups. The Kaplan–Meier method and double-robust Cox multivariable regression were run to estimate the survival and the risk of mortality and recurrence. Results: Between 2008 and 2022, 1,465 patients were enrolled. The laparoscopic resection group and ablation group consisted of 496 and 969 patients, respectively. At baseline, the ablation group had more advanced liver disease, with higher rates of cirrhosis (90.7% vs. 77.3%, p <0.001) and Child-Pugh B status (18.4% vs. 8.8%, p <0.001). After a median follow-up of 59 months and after weighting median overall survival was 60 months (95% CI 52–66) for the ablation group and 93 months (95% CI 75–110) for the laparoscopic resection group (hazard ratio [HR] 0.607, 95% CI 0.533–0.691, p <0.001). Median recurrence-free survival was 26 months (95% CI 23–29) for the ablation group and 39 months (95% CI 30–55) for the laparoscopic resection group (HR 0.736, 95% CI 0.659–0.822, p = 0.0013). Laparoscopy was associated with a reduced risk of early recurrence (HR 0.747, 95% CI 0.655–0.853, p = 0.011). Conclusions: This study provides real-world evidence that for patients with single ≤3 cm HCC, videolaparoscopic liver resection offers superior long-term oncological outcomes compared with thermoablation. These findings support the preference for surgical treatment in this patient population. Impact and implications: Percutaneous thermoablation is considered an appropriate alternative to liver resection for small (≤3 cm) single hepatocellular carcinoma because of not-inferior overall survival, although several authors reported increased recurrence risk. Whether videolaparoscopic liver resection could guarantee comparable survival but superior oncologic control of the disease is a matter of debate. This study comparing videolaparoscopy vs. thermoablation in a large national cohort of 1,465 patients observed that the former guaranteed significant prolonged OS (93 months [95% CI 75–110] vs. 60 months [95% CI 52–66] for the ablation group) and recurrence-free survival (26 months [95% CI 23–29] for ablation patients and 39 months [95% CI 30–55] for laparoscopic resection patients) even after weighting all the preoperative and oncologic differences among the groups. Our results clearly address the need to rethink the role of thermoablation for single small HCC as a second-line treatment when laparoscopic liver resection is not feasible.
Keywords