Evidence in Focus: The Sparse Landscape of Randomized Trials on Retinoblastoma Treatment

Background: Retinoblastoma, although rare, is one of the most common intraocular malignancies worldwide. Its prognosis has improved significantly in the past few decades, thanks to modern treatments, like systemic, intra-arterial, and intravitreal chemotherapy. However, regarding survival, there are significant differences between high- and low-income countries, eye salvage is still a challenge worldwide, and treatment-related toxicity needs to be carefully and sufficiently managed. Summary: To appraise the strength of supporting evidence, we performed a systematic review of randomized controlled trials investigating any therapeutic protocol for retinoblastoma. Four trials with 174 participants (188 eyes) were eligible, all pertaining to different intravenous chemotherapy regimens. Vincristine, etoposide, and carboplatin (VEC) appear superior to a 5-drug combination for stage III retinoblastoma. Moreover, etoposide and carboplatin as neoadjuvant chemotherapy followed by thermochemotherapy seem to offer better local control than vincristine and carboplatin. However, increasing carboplatin dose in the VEC protocol failed to improve treatment efficacy. Key Messages: Retinoblastoma is a success story of modern medicine. However, only intravenous chemotherapy has been studied through randomized trials, while evidence for the most novel retinoblastoma treatments has mainly stemmed from observational studies. International collaborations for multicenter randomized trials could overcome difficulties and increase certainty and precision in the field.