Metastatic Death Based on Presenting Features and Treatment for Advanced Intraocular Retinoblastoma: A Multicenter Registry-Based Study

Abstract

Purpose: To evaluate presenting features, tumor size, and treatment methods for risk of metastatic death due to advanced intraocular retinoblastoma (RB).

Design: International, multicenter, registry-based retrospective case series.

Participants: A total of 1841 patients with advanced RB.

Methods: Advanced RB was defined by 8th edition American Joint Committee on Cancer (AJCC) categories cT2 and cT3 and new AJCC-Ophthalmic Oncology Task Force (OOTF) Size Groups (1: < 50% of globe volume, 2: > 50% but < 2/3, 3: > 2/3, and 4: diffuse infiltrating RB). Treatments were primary enucleation, systemic chemotherapy with secondary enucleation, and systemic chemotherapy with eye salvage.

Main outcome measures: Metastatic death.

Results: The 5-year Kaplan-Meier cumulative survival estimates by patient-level AJCC clinical subcategories were 98% for cT2a, 96% for cT2b, 88% for cT3a, 95% for cT3b, 92% for cT3c, 84% for cT3d, and 75% for cT3e RB. Survival estimates by treatment modality were 96% for primary enucleation, 89% for systemic chemotherapy and secondary enucleation, and 90% for systemic chemotherapy with eye salvage. Risk of metastatic mortality increased with increasing cT subcategory (P < 0.001). Cox proportional hazards regression analysis confirmed a higher risk of metastatic mortality in categories cT3c (glaucoma, hazard ratio [HR], 4.9; P = 0.011), cT3d (intraocular hemorrhage, HR, 14.0; P < 0.001), and cT3e (orbital cellulitis, HR, 19.6; P < 0.001) than in category cT2a and with systemic chemotherapy with secondary enucleation (HR, 3.3; P < 0.001) and eye salvage (HR, 4.9; P < 0.001) than with primary enucleation. The 5-year Kaplan-Meier cumulative survival estimates by AJCC-OOTF Size Groups 1 to 4 were 99%, 96%, 94%, and 83%, respectively. Mortality from metastatic RB increased with increasing Size Group (P < 0.001). Cox proportional hazards regression analysis revealed that patients with Size Group 3 (HR, 10.0; P = 0.002) and 4 (HR, 41.1; P < 0.001) had a greater risk of metastatic mortality than Size Group 1.

Conclusions: The AJCC-RB cT2 and cT3 subcategories and size-based AJCC-OOTF Groups 3 (> 2/3 globe volume) and 4 (diffuse infiltrating RB) provided a robust stratification of clinical risk for metastatic death in advanced intraocular RB. Primary enucleation offered the highest survival rates for patients with advanced intraocular RB.

Keywords: AJCC; Advanced; Chemotherapy; Enucleation; International; Metastasis; Multicenter; Registry; Retinoblastoma; Staging.

Figure 1.

Consolidated Standards of Reporting Trials flow diagram of all patients with advanced retinoblastoma. AJCC = American Joint Committee on Cancer; OOTF = Ophthalmic Oncology Task Force; VT = vitreous hemorrhage.

Figure 2.

Kaplan–Meier curves showing cumulative survival estimates for patients with advanced retinoblastoma by American Joint Committee on Cancer (AJCC) clinical subcategory. T = tumor.

Figure 3.

Kaplan–Meier curves showing cumulative survival estimates for patients with advanced retinoblastoma by treatment modality.

Figure 4.

Kaplan–Meier curves showing cumulative survival estimates for patients with advanced retinoblastoma by American Joint Committee on Cancer (AJCC)-Ophthalmic Oncology Task Force (OOTF) Size Groups.