Management of Advanced Stage Retinoblastoma
Advanced stage retinoblastoma requires multimodal treatment combining systemic chemotherapy with focal consolidation therapies (laser photocoagulation, cryotherapy, thermotherapy), while avoiding external beam radiotherapy in hereditary cases due to significantly increased risk of secondary malignancies. 1, 2
Initial Assessment and Genetic Testing
- All children with retinoblastoma require germline RB1 testing regardless of whether disease is unilateral or bilateral, as approximately 15% of unilateral cases are hereditary 3, 4
- Examination under anesthesia is the standard for complete evaluation, with imaging studies used to assess extraocular extension 1
- Bilateral disease (30-40% of cases) always indicates hereditary retinoblastoma and presents earlier at 18-24 months versus unilateral disease at 36 months 1, 3
Treatment Algorithm for Advanced Disease
Primary Chemotherapy Approach
- Intravenous chemotherapy is the established standard for primary treatment of intraocular retinoblastoma, particularly for bilateral/hereditary cases with excellent tumor control for groups A, B, and C, and intermediate control for group D eyes 5, 2
- The chemoreduction strategy debulks tumor volume to allow subsequent focal consolidation therapies 6
Alternative Chemotherapy Routes for Advanced/Refractory Disease
- Intra-arterial chemotherapy serves as primary therapy for selected unilateral cases or secondary therapy for recurrent solid retinoblastoma, subretinal seeds, and vitreous seeds with excellent control rates 2, 7
- Periocular chemotherapy boosts local chemotherapy dose in advanced bilateral groups D and E eyes or for localized recurrences 2
- Intravitreal chemotherapy specifically targets recurrent vitreous seeds 2, 7
Focal Consolidation Therapies
- Transpupillary thermotherapy, laser photocoagulation, and cryotherapy are combined with chemotherapy for localized tumor control 1, 8, 7
- These modalities are applied after chemoreduction to treat residual disease 6
Critical Treatment Considerations
Radiation Therapy Restrictions
- External beam radiotherapy must be avoided when possible in hereditary cases due to a 10% per decade increased risk of second cancers in the radiation field 3
- Ophthalmic plaque brachytherapy provides more focal radiation with less risk but is limited to small-to-medium sized tumors in accessible locations 6
High-Risk Features Requiring Systemic Chemotherapy
- Optic nerve invasion beyond the cut end 6
- Scleral disruption with microscopic orbital tissue invasion 6
- Patients at high risk for metastases require intravenous chemotherapy regardless of local disease control 2
Enucleation Indications
- Large tumors with no useful vision expected 6
- Long-standing retinal detachments 6
- Neovascular glaucoma 6
- Suspected optic nerve invasion or extrascleral extension 6
Extraocular and Metastatic Disease
- Advanced extraocular or metastatic tumors have poor prognosis despite treatment 7
- Systemic and intrathecal chemotherapy combined with local and cranial radiotherapy improves survival in patients with disease beyond the optic nerve or orbital invasion 6
- Central nervous system involvement carries particularly poor prognosis 6
Long-Term Surveillance Requirements
- Survivors of hereditary retinoblastoma require lifelong skin examination for melanoma due to significantly increased risk of subsequent malignant neoplasms, particularly sarcomas and melanomas 1, 3
- Immediate evaluation of any signs or symptoms of head and neck disease is essential 1
- Genetic counseling for all hereditary cases regardless of germline testing results 3