Validation of a supplementary condition of eighth AJCC staging system for stage II hepatocellular carcinoma.

Introduction: The eighth American Joint Committee on Cancer (AJCC) staging system was flawed regarding the prognosis of stage II hepatocellular carcinoma (HCC). The aims of this study were to reveal the defect and make updates.

Methods: Clinical and survival data of HCC patients from the Surveillance, Epidemiology, and End Results database were used. We re-classified stage II into T2aN0M0 (tumors >2 cm with vascular invasion) and T2bN0M0 (multiple tumors ≤5 cm). The Kaplan-Meier method and log-rank test were used to estimate differences in overall survival (OS). Three propensity score matching analyses without (PSM1) or with (PSM2 and PSM3) consideration of surgical treatment were performed. Cox regression was used to reveal risk factors.

Results: HCC patients identified as T1bN0M0, T2aN0M0, T2bN0M0, and T3N0M0 were recruited. OS in T2N0M0 was consistent with the eighth AJCC staging system after PSM1. T2bN0M0 had increased OS compared with T2aN0M0 after PSM2 (hazard ratio [HR] = 1.36; 95% confidence interval [CI] = 1.06-1.73; P = 0.0141) or PSM3 (HR = 1.18; 95%CI = 1.01-1.37; P = 0.0283). No survival benefit existed between T1bN0M0 and T2bN0M0 after PSM2 (HR = 0.92; 95%CI = 0.80-1.05; P = 0.2171) or PSM3 (HR = 0.92; 95%CI = 0.84-1.01; P = 0.0888). Compared with T2aN0M0, T3N0M0 had shorter OS after PSM2 (HR = 0.64; 95%CI = 0.50-0.82; P = 0.0003) or PSM3 (HR = 0.63; 95%CI = 0.54-0.73; P < 0.0001). Cox regression analysis revealed that surgical treatment was associated with better prognosis (HR = 0.3; 95%CI = 0.3-0.4; P < 0.001).

Conclusions: The current staging for T2N0M0 is imprecise because surgical treatment is not adequately evaluated and would be ineffective if the proportion of T2bN0M0 patients with surgical treatment was increased.