Standard treatment options
Usually the disease is more advanced in one eye, with less involvement in the other eye. Overall treatment management is dictated by the most advanced eye. While up-front enucleation of an advanced eye and risk-adapted adjuvant chemotherapy may be required, a more conservative approach using primary chemoreduction with close follow-up for response and focal treatment (e.g., cryotherapy or laser therapy) may be indicated. EBRT is now reserved for patients whose eyes do not respond adequately to primary systemic chemotherapy and focal consolidation.
A number of large centers in Europe and North America have published trial results using systemic chemotherapy in conjunction with aggressive focal consolidation for patients with bilateral disease.[1,20,23,24,50,51,55,56,57,58,59,60,61,62,63]; [Level of evidence: 3iiDiv] Chemotherapy may shrink the tumors (chemoreduction), allowing greater efficacy of subsequent focal therapy.[1,40] Treatment strategies often differ in terms of chemotherapy regimens and local control measures.
Centers using the R-E classification have demonstrated that the goal to save eyes may be achievable for tumors that are R-E Group IV or lower. The backbone of the chemoreduction protocols has generally been carboplatin, etoposide, and vincristine (CEV). Studies from The Children's Hospital of Philadelphia and Wills Eye Hospital reported that enucleation or EBRT may be avoided in R-E Group I, II, and III eyes when patients were treated with six cycles.[1,12,21] Tumors associated with massive vitreous or subretinal seeds have proven problematic. Local control was often transient in patients with vitreous seeding or very large tumors (R-E Group V), and fewer than half of patients were treated successfully without requiring EBRT and/or enucleation.[1,12]
Other researchers reported the use of nine courses of CEV with the addition of high-dose cyclosporine A (a modulator of the p-glycoprotein) for eight R-E Group V eyes with an 88% (7 out of 8 eyes) success rate without the use of EBRT or enucleation.[58,59] However, conflicting results were seen in another study using the cyclosporine regimen in ten R-E Group V eyes, which reported only a 20% (2 out of 10 eyes) success rate.
The International Classification system for staging intraocular retinoblastoma is a better predictor of treatment success for the use of systemic chemotherapy in combination with local control. (Refer to the Treatment Options Under Clinical Evaluation section of this summary for a more complete description of the International Classification system.) The combinations of carboplatin and etoposide (CE) [22,65] or CEV [66,67] in conjunction with local control have resulted in ocular salvage rates above 90% for early intraocular disease (Groups A and B eyes), 70% to 90% for Group C eyes, and 40% to 50% for Group D eyes.[22,65,67]; [Level of evidence: 3iiDiv] However, for patients with advanced intraocular disease (typically Group D eyes), EBRT is frequently required for ocular salvage.; [Level of evidence: 3iiDiii]