Treatment of Bilateral Intraocular Retinoblastoma

The goal of therapy for bilateral retinoblastoma is ocular and vision preservation and the delay or avoidance of EBRT and enucleation.

Treatment options for bilateral intraocular retinoblastoma include the following:

Intraocular tumor burden is usually asymmetrical, and treatment is dictated by the most advanced eye. Systemic therapy is generally selected based on the eye with more extensive disease. Treatment options described for unilateral disease may be applied to one or both affected eyes in patients with bilateral disease. While up-front enucleation of an advanced eye and risk-adapted adjuvant chemotherapy may be required, a more conservative approach using primary chemoreduction and aggressive local treatments with close monitoring for response is usually the treatment of choice. EBRT is now reserved for patients whose eyes do not respond adequately to primary systemic or intra-arterial chemotherapy and local consolidation.[20]

Several large centers have published trial results that used systemic chemotherapy in conjunction with aggressive local consolidation for patients with bilateral disease.[21] The backbone of chemoreduction has generally been carboplatin, etoposide, and vincristine. While the less toxic combination of vincristine and carboplatin can provide disease control for a significant proportion of patients, ocular salvage appears to be superior when etoposide is included in the regimen.[22][Level of evidence B1] A single-institution study achieved similar results when topotecan was substituted for etoposide in a combination regimen.[23][Level of evidence C1] Using chemoreduction and aggressive local control consolidation, the International Classification of Retinoblastoma grouping system has been proven to predict ocular survival, with globe salvage rates usually exceeding 80% for Groups A and B, and 40% to 80% for Groups C and D, although EBRT may be required in more advanced intraocular cases.[24]; [21,23][Level of evidence C1]

Delivery of chemotherapy via ophthalmic artery cannulation with the addition of intra-vitreal chemotherapy for patients with persistent vitreous or subretinal disease has become a very strong alternative to the use of systemic chemotherapy.[13,14,16,17]; [15][Level of evidence C3] While tandem administration is feasible, bilateral administrations increase the risk of systemic toxicity caused by melphalan exposure.[25] In these circumstances, intra-arterial chemotherapy with single-agent carboplatin may be used to treat the less-advanced eye during the tandem procedure.[26] These treatments should only be performed in an experienced center with a state-of-the-art treatment infrastructure and a dedicated multidisciplinary team. For more information, see the sections on Intra-Arterial Chemotherapy (Ophthalmic Artery Infusion of Chemotherapy) and Intravitreal Chemotherapy.

For patients with large intraocular tumor burdens with subretinal or vitreous seeds (Group D eyes), the administration of higher doses of carboplatin coupled with subtenon carboplatin, and the addition of lower doses of EBRT (36 Gy) for patients with persistent disease has been explored. Using this intensive approach, eye survival may approach a rate of 70% at 60 months.[27][Level of evidence B4]

The prognosis for patients with Group E eyes who are treated with systemic chemotherapy and local control measures is very poor without radiation therapy.[27][Level of evidence B4] The use of prolonged systemic chemotherapy for Group E eyes to avoid or delay enucleation has been associated with lower disease-specific survival.[12][Level of evidence C1]