Filippo Pelizzaro1, Barbara Penzo1, Giulia Peserico1, Angela Imondi1, Anna Sartori1, Alessandro Vitale2, Umberto Cillo2, Edoardo G Giannini3, Antonella Forgione4, Gian Ludovico Rapaccini5, Maria Di Marco6, Eugenio Caturelli7, Marco Zoli8, Rodolfo Sacco9, Giuseppe Cabibbo10, Fabio Marra11, Andrea Mega12, Filomena Morisco13, Antonio Gasbarrini14, Gianluca Svegliati-Baroni15, Francesco Giuseppe Foschi16, Andrea Olivani17, Alberto Masotto18, Gerardo Nardone19, Giovanni Raimondo20, Francesco Azzaroli21, Gianpaolo Vidili22, Filippo Oliveri23, Franco Trevisani24, Fabio Farinati1. 1. Department of Surgery, Oncology and Gastroenterology, Gastroenterology Unit, University of Padova, Padova, Italy. 2. Department of Surgery, Oncology and Gastroenterology, Hepatobiliary Surgery and Liver Transplantation Unit, University of Padova, Padova, Italy. 3. Department of Internal Medicine, Gastroenterology Unit, University of Genova, IRCCS Policlinico San Martino, Genova, Italy. 4. Internal Medicine-Piscaglia Unit, Azienda Ospedaliero-Universitaria S. Orsola-Malpighi, Bologna, Italy. 5. Gastroenterology Unit, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Roma, Italy. 6. Medicine Unit, Bolognini Hospital, Seriate, Italy. 7. Gastroenterology Unit, Belcolle Hospital, Viterbo, Italy. 8. Department of Medical and Surgical Sciences, Internal Medicine-Zoli Unit, Alma Mater Studiorum-University of Bologna, Bologna, Italy. 9. Gastroenterology and Digestive Endoscopy Unit, Foggia University Hospital, Foggia, Italy. 10. Department of Health Promotion, Mother & Child Care, Internal Medicine & Medical Specialties, PROMISE, Gastroenterology & Hepatology Unit, University of Palermo, Palermo, Italy. 11. Department of Experimental and Clinical Medicine, Internal Medicine and Hepatology Unit, University of Firenze, Firenze, Italy. 12. Gastroenterology Unit, Bolzano Regional Hospital, Bolzano, Italy. 13. Department of Clinical Medicine and Surgery, Gastroenterology Unit, University of Napoli "Federico II", Napoli, Italy. 14. Internal Medicine and Gastroenterology Unit, Policlinico Gemelli, Università Cattolica del Sacro Cuore, Roma, Italy. 15. Gastroenterology Unit, Polytechnic University of Marche, Ancona, Italy. 16. Department of Internal Medicine, Ospedale per gli Infermi di Faenza, Faenza, Italy. 17. Infectious Diseases and Hepatology Unit, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy. 18. Gastroenterology Unit, Ospedale Sacro Cuore Don Calabria, Negrar, Italy. 19. Department of Clinical Medicine and Surgery, Hepato-Gastroenterology Unit, University of Napoli "Federico II", Napoli, Italy. 20. Department of Clinical and Experimental Medicine, Clinical and Molecular Hepatology Unit, University of Messina, Messina, Italy. 21. Department of Surgical and Medical Sciences, Gastroenterology Unit, Alma Mater Studiorum-University of Bologna, Bologna, Italy. 22. Department of Medical, Surgical and Experimental Science, Clinica Medica Unit, University of Sassari, Azienda Ospedaliero-Universitaria di Sassari, Sassari, Italy. 23. Department of Clinical and Experimental Medicine, Hepatology and Liver Physiopathology Laboratory and Internal Medicine, University of Pisa, Pisa, Italy. 24. Department of Medical and Surgical Sciences, Semeiotics Unit, Alma Mater Studiorum-University of Bologna, Bologna, Italy.
Abstract
BACKGROUND & AIMS: According to the Barcelona Clinic Liver Cancer (BCLC) staging system, monofocal hepatocellular carcinoma (HCC) is classified as early (BCLC A) irrespective of its size, even though controversies still exist regarding staging and treatment of large tumours. We aimed at evaluating the appropriate staging and treatment for large (>5 cm) monofocal (HCC). METHODS: From the Italian Liver Cancer database, we selected 924 patients with small early monofocal HCC (2-5 cm; SEM-HCC), 163 patients with larger tumours (>5 cm; LEM-HCC) and 1048 intermediate stage patients (BCLC B). RESULTS: LEM-HCC patients had a worse overall survival (OS) than SEM-HCC (31.0 vs 49.0 months; P < .0001), and this was confirmed at multivariate analysis (HR 1.63, 95% CI 1.29-2.05; P < .0001). The small difference in OS between LEM-HCC and BCLC B patients (31.0 vs 27.0 months; P = .03) disappeared in the multivariate model (HR 0.98, 95% CI 0.77-1.25; P = .89). In all monofocal tumours, treatment was the strongest independent predictor of survival, with a progressively decreasing survival benefit moving from "curative" to "palliative" therapies. The survival of resected patients with LEM-HCC was significantly shorter than that of SEM-HCC (44.0 vs 78.0 months; P = .002), but liver resection provided the highest survival benefit in both groups compared to other treatments. CONCLUSIONS: Monofocal HCC larger than 5 cm should not be staged as BCLC A and either a different staging system or a different subgrouping of patients (e.g. BCLC AB) should be used. Liver resection, if feasible, remains the recommended treatment for all these patients.
BACKGROUND & AIMS: According to the Barcelona Clinic Liver Cancer (BCLC) staging system, monofocal hepatocellular carcinoma (HCC) is classified as early (BCLC A) irrespective of its size, even though controversies still exist regarding staging and treatment of large tumours. We aimed at evaluating the appropriate staging and treatment for large (>5 cm) monofocal (HCC). METHODS: From the Italian Liver Cancer database, we selected 924 patients with small early monofocal HCC (2-5 cm; SEM-HCC), 163 patients with larger tumours (>5 cm; LEM-HCC) and 1048 intermediate stage patients (BCLC B). RESULTS: LEM-HCC patients had a worse overall survival (OS) than SEM-HCC (31.0 vs 49.0 months; P < .0001), and this was confirmed at multivariate analysis (HR 1.63, 95% CI 1.29-2.05; P < .0001). The small difference in OS between LEM-HCC and BCLC B patients (31.0 vs 27.0 months; P = .03) disappeared in the multivariate model (HR 0.98, 95% CI 0.77-1.25; P = .89). In all monofocal tumours, treatment was the strongest independent predictor of survival, with a progressively decreasing survival benefit moving from "curative" to "palliative" therapies. The survival of resected patients with LEM-HCC was significantly shorter than that of SEM-HCC (44.0 vs 78.0 months; P = .002), but liver resection provided the highest survival benefit in both groups compared to other treatments. CONCLUSIONS: Monofocal HCC larger than 5 cm should not be staged as BCLC A and either a different staging system or a different subgrouping of patients (e.g. BCLC AB) should be used. Liver resection, if feasible, remains the recommended treatment for all these patients.