Retinoblastoma with and without Extraocular Tumor Extension: A Global Comparative Study of 3435 Patients.

Purpose: To study the treatment and outcomes of children with retinoblastoma (RB) with extraocular tumor extension (RB-EOE) and compare them with RB without extraocular tumor extension (RB-w/o-EOE). Design: Multicenter intercontinental collaborative prospective study from 2017 to 2020. RB-EOE cases included those with overt orbital tumor extension in treatment-naive patients. Cases with microscopic orbital extension detected postenucleation were excluded from the study. Participants: A total of 319 children with RB-EOE and 3116 children with RB-w/o-EOE. Intervention: Chemotherapy, enucleation, exenteration, radiotherapy. Main Outcome Measures: Systemic metastasis and death. Results: Of the 3435 RB patients included in this study, 309 (9%) were from low-income countries (LIC), 1448 (42%) from lower-middle income, 1012 (29%) from upper-middle income, and 666 (19%) patients from high-income countries. There was an inverse relationship between the percentage of RB-EOE and national income level, with 96 (31%) patients from LIC, 197 (6%) lower-middle income, 20 (2%) upper-middle income, and 6 (1%) patients from high-income countries ( Conclusions: Retinoblastoma with extraocular tumor extension is associated with a higher risk of metastasis and death. Patients with RB-EOE are likely to benefit from trimodal treatment (intravenous chemotherapy, surgery, and EBRT) rather than treatment protocols excluding EBRT. Financial Disclosures: The authors have no proprietary or commercial interest in any materials discussed in this article.