Predictors of non‐transplantable recurrence in hepatocellular carcinoma patients treated with frontline liver resection

Author:

Pelizzaro Filippo12ORCID,Trevisani Franco34ORCID,Simeon Vittorio5,Vitale Alessandro16ORCID,Cillo Umberto16,Piscaglia Fabio7ORCID,Missale Gabriele8ORCID,Sangiovanni Angelo9ORCID,Foschi Francesco G.10,Cabibbo Giuseppe11,Caturelli Eugenio12,Di Marco Maria13,Azzaroli Francesco14,Brunetto Maurizia R.15ORCID,Raimondo Giovanni16ORCID,Vidili Gianpaolo17ORCID,Guarino Maria18ORCID,Gasbarrini Antonio19ORCID,Campani Claudia20ORCID,Svegliati‐Baroni Gianluca21ORCID,Giannini Edoardo G.22ORCID,Mega Andrea23,Masotto Alberto24,Rapaccini Gian Ludovico19,Magalotti Donatella25,Sacco Rodolfo26,Nardone Gerardo27ORCID,Farinati Fabio12ORCID,

Affiliation:

1. Department of Surgery, Oncology and Gastroenterology University of Padova Padova Italy

2. Gastroenterology Unit Azienda Ospedale‐Università di Padova Padova Italy

3. Unit of Semeiotics, Liver and Alcohol‐related diseases, Department of Medical and Surgical Sciences Università di Bologna Bologna Italy

4. Unit of Semeiotics, Liver and Alcohol‐Related Diseases IRCCS Azienda Ospedaliero‐Universitaria di Bologna Bologna Italy

5. Medical Statistics Unit, Mental, Physical Health and Preventive Medicine University of Campania ‘Luigi Vanvitelli’ Napoli Italy

6. Hepatobiliary Surgery and Liver Transplantation Unit Azienda Ospedale‐Università di Padova Padova Italy

7. Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases IRCCS Azienda Ospedaliero‐Universitaria di Bologna Bologna Italy

8. Department of Medicine and Surgery, Unit of Infectious Diseases and Hepatology University of Parma Parma Italy

9. Division of Gastroenterology and Hepatology Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milan Italy

10. Department of Internal Medicine Ospedale per gli Infermi di Faenza Faenza Italy

11. Department of Health Promotion, Mother & Child Care, Internal Medicine & Medical Specialties, PROMISE, Gastroenterology & Hepatology Unit University of Palermo Palermo Italy

12. Gastroenterology Unit Belcolle Hospital Viterbo Italy

13. Medicine Unit Bolognini Hospital Seriate Italy

14. Gastroenterology Unit, Department of Surgical and Medical Sciences IRCCS Azienda Ospedaliero‐Universitaria di Bologna Bologna Italy

15. Department of Clinical and Experimental Medicine, Hepatology and Liver Physiopathology Laboratory and Internal Medicine Unit University of Pisa Pisa Italy

16. Department of Clinical and Experimental Medicine, Clinical and Molecular Hepatology Unit University of Messina Messina Italy

17. Department of Medicine Surgery and Pharmacy, Centralized Day Hospital of the medical area University of Sassari, Azienda Ospedaliero‐Universitaria di Sassari Sassari Italy

18. Department of Clinical Medicine and Surgery, Diseases of the Liver and Biliary System Unit University of Napoli ‘Federico II’ Napoli Italy

19. Internal Medicine and Gastroenterology Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore Roma Italy

20. Department of Experimental and Clinical Medicine, Internal Medicine and Hepatology Unit University of Firenze Firenze Italy

21. Gastroenterology Unit Polytechnic University of Marche Ancona Italy

22. Gastroenterology Unit, Department of Internal Medicine University of Genova, IRCCS Ospedale Policlinico San Martino Genova Italy

23. Gastroenterology Unit Bolzano Regional Hospital Bolzano Italy

24. Gastroenterology Unit Ospedale Sacro Cuore Don Calabria Negrar Italy

25. Division of Internal Medicine, Neurovascular and Hepatometabolic Diseases IRCCS Azienda Ospedaliero‐Universitaria di Bologna Bologna Italy

26. Gastroenterology and Digestive Endoscopy Unit Foggia University Hospital Foggia Italy

27. Department of Clinical Medicine and Surgery, Hepato‐Gastroenterology Unit University of Napoli ‘Federico II’ Napoli Italy

Abstract

AbstractBackground and AimsHepatocellular carcinoma (HCC) recurrence is common in patients treated with liver resection (LR). In this study, we aimed to evaluate the incidence and preoperative predictors of non‐transplantable recurrence in patients with single HCC ≤5 cm treated with frontline LR.MethodsFrom the Italian Liver Cancer (ITA.LI.CA) database, 512 patients receiving frontline LR for single HCC ≤5 cm were retrieved. Incidence and predictors of recurrence beyond Milan criteria (MC) and up‐to‐seven criteria were compared between patients with HCC <4 and ≥4 cm.ResultsDuring a median follow‐up of 4.2 years, the overall recurrence rate was 55.9%. In the ≥4 cm group, a significantly higher proportion of patients recurred beyond MC at first recurrence (28.9% vs. 14.1%; p < 0.001) and overall (44.4% vs. 25.2%; p < 0.001). Similar results were found considering recurrence beyond up‐to‐seven criteria. Compared to those with larger tumours, patients with HCC <4 cm had a longer recurrence‐free survival and overall survival. HCC size ≥4 cm and high alpha‐fetoprotein (AFP) level at the time of LR were independent predictors of recurrence beyond MC (and up‐to‐seven criteria). In the subgroup of patients with available histologic information (n = 354), microvascular invasion and microsatellite lesions were identified as additional independent risk factors for non‐transplantable recurrence.ConclusionsDespite the high recurrence rate, LR for single HCC ≤5 cm offers excellent long‐term survival. Non‐transplantable recurrence is predicted by HCC size and AFP levels, among pre‐operatively available variables. High‐risk patients could be considered for frontline LT or listed for transplantation even before recurrence.

Publisher

Wiley

Subject

Hepatology

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