Background Although the Barcelona Clinic Liver Cancer (BCLC) staging system has been largely adopted in clinical practice, recent studies have emphasized the need for further refinement and subclassification of this system. Methods Patients who underwent hepatectomy with curative intent for BCLC-0, -A or -B hepatocellular carcinoma (HCC) between 2000 and 2017 were identified using a multi-institutional database. The tumour burden score (TBS) was calculated, and overall survival (OS) was examined in relation to TBS and BCLC stage. Results Among 1053 patients, 63 (6 center dot 0 per cent) had BCLC-0, 826 (78 center dot 4 per cent) BCLC-A and 164 (15 center dot 6 per cent) had BCLC-B HCC. OS worsened incrementally with higher TBS (5-year OS 77 center dot 9, 61 and 39 per cent for low, medium and high TBS respectively; P < 0 center dot 001). No differences in OS were noted among patients with similar TBS, irrespective of BCLC stage (61 center dot 6 versus 58 center dot 9 per cent for BCLC-A/medium TBS versus BCLC-B/medium TBS, P = 0 center dot 930; 45 versus 13 per cent for BCLC-A/high TBS versus BCLC-B/high TBS, P = 0 center dot 175). Patients with BCLC-B HCC and a medium TBS had better OS than those with BCLC-A disease and a high TBS (58 center dot 9 versus 45 per cent; P = 0 center dot 005). On multivariable analysis, TBS remained associated with OS among patients with BCLC-A (medium TBS: hazard ratio (HR) 2 center dot 07, 95 per cent c.i. 1 center dot 42 to 3 center dot 02, P < 0 center dot 001; high TBS: HR 4 center dot 05, 2 center dot 40 to 6 center dot 82, P < 0 center dot 001) and BCLC-B (high TBS: HR 3 center dot 85, 2 center dot 03 to 7 center dot 30; P < 0 center dot 001) HCC. TBS could also stratify prognosis among patients in an external validation cohort (5-year OS 79, 51 center dot 2 and 28 per cent for low, medium and high TBS respectively; P = 0 center dot 010). Conclusion The prognosis of patients with HCC varied according to the BCLC stage but was largely dependent on the TBS.
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