Continuing challenges in the management of retinoblastoma with chemotherapy.

The management of retinoblastoma has gradually changed over the past 10 years. Over 95% of children with retinoblastoma in the United States are cured with modern techniques. The challenge remains, however, in maintaining the eye and vision. There is a trend away from enucleation and external beam radiotherapy toward focal conservative treatments involving primary chemoreduction in conjunction with thermotherapy and cryotherapy. This is related to earlier detection of the disease, recognition of more effective chemotherapeutic agents, more focused local treatment modalities, and, most importantly, knowledge of the long-term risks of external beam radiotherapy. Enucleation is still preferable for retinoblastoma that fills most of the eye, especially when the disease is unilateral or when there is concern for tumor invasion into the optic nerve, choroid, or orbit. The orbital integrated implant is placed after enucleation and provides acceptable prosthesis motility and appearance. External beam radiotherapy is still vital for treating advanced retinoblastoma, especially when there is diffuse vitreous or subretinal seeding after failure of other methods and preservation of vision is a priority. The most important recent advance in the management of retinoblastoma is the use of intravenous chemotherapy for tumor reduction, a technique of neoadjuvant chemotherapy termed "chemoreduction." This is followed by tumor consolidation with focal measures such as thermotherapy, cryotherapy, and plaque radiotherapy. This strategy provides reduced tumor volume and often permits consolidation with methods other than radiotherapy. It appears that vision can be preserved in some cases with these methods, avoiding some of the local complications like radiation cataract or macular edema that have been found with radiotherapy techniques. External beam radiotherapy and enucleation can now be avoided in most cases of Reese-Ellsworth groups I (minimal disease) through IV (moderate disease) retinoblastoma. The most advanced stage of retinoblastoma, Reese-Ellsworth group V, continues to provide the greatest difficulty for management, and external beam radiotherapy and enucleation are often employed in addition to chemoreduction to save the child's life. A collaborative prospective study in North America is currently under way to further study the benefits and risks of chemoreduction for minimal, moderate, and advanced retinoblastoma.