Therapeutic Options for Retinoblastoma

Pia R. Mendoza, MD; Hans E. Grossniklaus, MD


Cancer Control. 2016;23(2):99-109. 

In This Article

Concepts and Principles of Treatment

The goal of treatment in retinoblastoma is the elimination of the tumor while concurrently minimizing collateral injury to other tissues. The priorities in management are (1) preventing metastasis, (2) reducing the risk of long-term secondary tumors (eg, osteosarcoma, soft-tissue sarcoma), (3) saving the eye, and (4) preserving vision.[11] Caring for a patient with retinoblastoma must be a multidisciplinary effort involving pediatric oncologists, ocular oncologists, radiation oncologists, ocular pathologists, and geneticists to optimize treatment outcomes.

Treatment depends on tumor stage, laterality and number of tumor foci (unifocal, unilateral, multifocal, or bilateral), the localization and size of tumors within the eye, presence of vitreous seeding, age and health of the child, and the family's wishes.[12] The type of management depends on the tumor classification, which is based on 2 systems: the International Classification of Retinoblastoma[13] used to predict success of chemoreduction[14] and the tumor, node, and metastasis classification of the American Joint Committee on Cancer[15] for tumor staging (Table 2). Location of the tumor in relation to the optic disc and macula is important in the clinical evaluation because it largely affects the visual prognosis. Involvement of certain tissues in and around the eye, including the optic nerve, choroid, iris, sclera, and orbit, increase the likelihood of tumor metastasis.[16]

In children, unilateral retinoblastoma is differently managed than bilateral tumors. In general, unilateral cases are the result of sporadic mutations, whereas bilateral cases are typically multifocal, hereditary, and occur in patients carrying a germline RB1 mutation, thus placing them at risk for other malignancies (eg, intracranial neuroblastic tumors [pinealoblastoma in trilateral retinoblastoma]). In general, unilateral tumors can be managed with focal therapy alone; chemoreduction, intra-arterial chemotherapy with focal therapy, or both; or enucleation. If genetic testing is not performed, then patients with unilateral disease require close follow-up of the unaffected eye to exclude bilateral involvement. Alternatively, treatment for bilateral tumors will depend on the extent of tumor in each eye. In asymmetric disease, an attempt is made to salvage the eye with less severe disease. One may consider giving patients systemic intravenous chemoreduction as initial therapy to treat both eyes as well as to prevent metastasis and associated secondary tumors or to use local (intra-arterial) chemotherapy with focal treatment.[7,17,18]

Initial chemotherapy in retinoblastoma can be given either systemically (intravenous) or locally (directly through the ophthalmic artery/intra-arterial). Chemoreduction is then usually followed by consolidation, which is achieved by focal therapy (eg, laser photocoagulation, thermotherapy, cryotherapy, plaque brachytherapy). Focal therapy may be employed as the only or initial therapy for small retinoblastoma tumors located away from the fovea and optic nerve (group A); it is often used for tumor consolidation in retinoblastoma following chemoreduction for more advanced (groups B–D) tumors. Surgical removal of the eye or enucleation is reserved for very advanced (group E) cases.