Bilateral Conversion Risk in Unilateral Retinoblastoma Using Age and Genetic Testing

Area of Science:

• Ophthalmology
• Genetics
• Pediatric Oncology

Background:

• Metachronous bilateral retinoblastoma conversion, though uncommon, carries significant clinical implications and a poorer prognosis.
• Refining genetic risk stratification by age at diagnosis is crucial for optimizing surveillance protocols.

Purpose of the Study:

• To determine the incidence and timing of metachronous bilateral conversion in unilateral retinoblastoma.
• To assess the association between age at diagnosis, RB1 testing, and the risk of bilateral conversion.

Main Methods:

• Retrospective cohort study of 1108 children with initially unilateral retinoblastoma.
• Analysis of age at diagnosis and RB1 genetic status (including penetrance and mosaicism) using next-generation sequencing and MLPA.
• Evaluation of time to conversion and cumulative incidence with death as a competing risk.

Main Results:

• 2.2% of patients developed metachronous bilateral disease; 24-month cumulative incidence was 2.2%.
• RB1 variant-positive patients had a significantly higher 24-month cumulative incidence (24.8%) compared to RB1 variant-negative patients (1.6%).
• In RB1 variant-positive cases, conversion risk was concentrated in those diagnosed before 9 months; rare late conversions occurred in RB1 variant-negative patients.

Conclusions:

• Age at diagnosis can refine genetic risk stratification for metachronous bilateral retinoblastoma conversion.
• RB1 variant-positive patients diagnosed at 9 months or older may represent a low-risk subgroup warranting surveillance de-escalation.
• Continued long-term monitoring is essential for RB1 variant-negative patients due to rare late conversions.