Challenging a dogma; AJCC 8th staging system is not sufficient to predict outcomes of patients with malignant pleural mesothelioma

Background: The 8th edition of malignant pleural mesothelioma (MPM) American Joint Committee on Cancer (AJCC) staging system has been published. The current analysis aims to evaluate its performance in a population-based setting among patients recorded within the surveillance, epidemiology and end results (SEER) database. Methods: SEER database (2004-2013) has been accessed through SEER*Stat program and AJCC 8th edition stage groups were reconstructed. Survival analyses (overall and cancer-specific) were conducted according to 6th and 8th editions through Kaplan-Meier analysis. Cox-regression multivariate model was also utilized for pair wise comparisons between different prognostic groups for overall and cancer-specific survival. Results: A total of 5382 patients with MPM were identified in the period from 2004 to 2013. According to the 6th edition, significant pair wise P values for overall survival included: IA vs. III (P = 0.027); IA vs. IV: P < 0.0001; IB vs. IV: P < 0.0001; II vs. III: P< 0.0001; II vs. IV: P < 0.0001; III vs. IV: P < 0.0001). According to the 8th edition, significant pair wise P values for overall survival included: all stages vs. IV: P < 0.0001; IA vs. II: P = 0.046; IA vs. IIIA: P = 0.022; IA vs. IIIB: P< 0.0001; IB vs. II: P < 0.0001; IB vs. IIIB: P < 0.0001; II vs. IIIA: P < 0.0001; IIIA vs. IIIB: P < 0.0001). C-index for 6th edition was 0.539 (SE: 0.008; 95% CI: 0.524-0.555); while C-index for 8th edition was 0.540 (SE: 0.008; 95% CI: 0.525-0.556). Based on the above findings, a simplified staging system was proposed and overall and cancer-specific survivals were evaluated according to the simplified system. For overall and cancer-specific survival assessment, P values for all pair wise comparisons among different stages were significant (< 0.01). Conclusion: The prognostic performance of both the 6th and 8th AJCC editions is unsatisfactory; there is a need for a more practical and prognostically relevant staging system for MPM.