A Proposal for Future Modifications on Clinical TNM Staging System of Retinoblastoma Based on the American Joint Committee on Cancer Staging Manual, 7(th) and 8(th) Editions

Importance: The 8(th) edition of the American Joint Committee on Cancer (AJCC) staging manual incorporated new changes from its 7(th) edition for classifying retinoblastoma (RB). Objective: We assessed the comparative prognostic values of the 7(th) and 8(th) editions of the AJCC clinical (cTNM) staging manuals for RB and suggested modifications for future edition accordingly. Design: A retrospective, observational study. Setting: King Hussein Cancer Centre. Participants: A cohort of 478 patients and 565 eyes with RB. Main Outcomes and Measures: Main outcome measures included demographics; tumor features, AJCC cTNM stage, and eye salvage rates. The prognostic performance of the different staging systems was assessed with the concordance index (C-index) and likelihood ratio χ(2) tests. Results: The overall eye salvage rate was 65%. Stage migration occurred for 330 (48%) eyes with the AJCC Staging Manual, 8(th) edition. Based on the 7(th) edition AJCC staging, the eye salvage rate was 94% (n=177) for T1 tumors (98% for T1a, 93%for T1b, and 90%for T1c), 69% (n=204) for T2 tumors (73% for T2a and 62%for T2b), and 51% (n=40) for T3 tumors. Based on the 8(th) edition AJCC staging, the eye salvage rate was 95% (n=139) for T1 tumors (98% for T1a and 93% for T1b), 68% (n=281) for T2 tumors (90%for T2a and 66%for T2b), and 12% (n=1) for T3 tumors. With our proposed cTNM modifications, the eye salvage rate was 94% (n=177) for T1 tumors (98%for T1a, 93%for T1b, and 90% for T1c), 66% (n=243) for T2 tumors (73% for T2a, 62% for T2b, and 55% for T2c), and 12% (n=1) for T3 tumors. As estimated by odds ratios, more advanced cTNM stage (regardless of the cTNM staging system) was significantly associated with an increased chance of treatment failure (P < .0001). The C-index for both the 8(th) edition and the proposed modifications were approximately equal, and both were higher than that of the 7(th) edition. However, the proposed modifications had the highest likelihood ratio χ(2) value and the best bootstrap 95% confidence interval. Conclusions and Relevance: Our proposed modifications on the clinical TNM Staging System for RB harbor more detailed subgroup classification criteria that provides better prognostic value for eye globe salvage than the published similar (but not identical) AJCC Staging Manual, 7(th) and 8(th) editions, furthermore these modifications may resolve the discrepancies in the previously published different classification systems for RB.