Natural History of Untreated Retinoblastoma

SIMPLE SUMMARY: Treatment abandonment is a leading cause of mortality for children with retinoblastoma worldwide. Noncompliance is influenced by both clinical and social factors including parents’ lack of appreciation of the aggressive nature of the disease. The natural history of retinoblastoma has not been previously studied because it is unethical to subject children with active cancer to nonintervention, and children who abandoned treatment were often lost to follow-up. Through phone interviews with families of children who abandoned treatment, we deduced the timeline of uninterrupted retinoblastoma disease progression. We showed that intraocular retinoblastoma progress to orbital extension had a median period of 13.7 months, from orbital disease to systemic metastasis 2.6 months and with only 2.0 months to death. If left untreated, 100% of children died within 48 months from diagnosis. We hope these new findings encourage clinicians and parents to make informed decisions in the management of children with retinoblastoma. ABSTRACT: Treatment abandonment is a leading cause of death in children with retinoblastoma worldwide. We studied children who abandoned treatment upfront at diagnosis to delineate the natural history of untreated retinoblastoma. Studied were children who received no treatment, diagnosed between 2007 and 2017 at 29 Chinese centers. Data were retrospectively collected from medical chart reviews and interviews with each patient’s family. During the study period, 44 children received no treatment after diagnosis of retinoblastoma. Clinical or radiologic evidence of orbital extension was available for 25 children, and radiologic evidence of systemic metastasis was available for 12 children. Median times from diagnosis of intraocular tumor to orbital disease was 13.7 months, orbital disease to metastasis was 2.6 months, and metastasis to death was 2.0 months. Children with brain metastasis had shorter survival than those with metastasis to other sites (median 1.0 vs. 3.1 months; p = 0.015). Overall, 36% of patients died within 12 months of diagnosis, 77% within 24 months, 95% within 36 months and 100% within 48 months. While multiple factors influence refusal of treatment, insights into the natural history of retinoblastoma derived from real-world evidence can inform clinicians and parents that retinoblastoma is life-threatening and encourage urgent treatment at diagnosis.