Therapeutic Options for Retinoblastoma

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


Cancer Control. 2016;23(2):99-109. 

In This Article

Abstract and Introduction


Background: Retinoblastoma is the most common primary intraocular malignancy in children. The management of retinoblastoma is complex and depends on several factors.

Methods: This review provides an update on current and emerging therapeutic options for retinoblastoma. The medical literature was searched for articles relevant to the management of retinoblastoma. The results of prospective and retrospective studies on chemotherapy and focal therapy for retinoblastoma are summarized. Animal models for novel therapeutic agents are also discussed.

Results: Treatment strategies for retinoblastoma involve intravenous chemoreduction, local administration routes of chemotherapy (eg, intra-arterial, intravitreal), focal therapy for tumor consolidation (eg, photocoagulation, thermotherapy, cryotherapy, plaque brachytherapy), external beam radiotherapy, and surgical enucleation. Emerging therapies include alternative chemotherapeutic agents, molecularly targeted therapies, and novel drug-delivery systems.

Conclusion: In the past 10 years, the management strategy for retinoblastoma has significantly changed, shifting toward local chemotherapy and away from systemic chemotherapy. Innovations in the field of molecular biology and the development of targeted therapies have led to improvements in survival rates and ocular salvage for this disease. However, the need still exists to further assess the long-term effects of such directional changes in therapy.


Retinoblastoma is the most common primary intraocular malignancy in children; its incidence rate is 1 in 14,000 to 20,000 livebirths.[1] However, compared with other pediatric malignancies, retinoblastoma is rare, comprising 3% to 4% of all pediatric cancers.[2] It is a tumor of the developing retina that arises from primitive retinal stem cells or cone precursor cells associated with inactivation of both alleles of the tumor suppressor gene RB1. Major advances, such as our understanding of the molecular biology of the tumor and the development of targeted therapy, have improved survival rates in developed countries.[3] In the United States, the 5-year overall survival rate is 97%.[4] Much of this success is due to the benefits of effective treatments, including chemotherapy, focal or consolidation therapy, external beam radiotherapy, and surgical enucleation (Table 1).[5] With early diagnosis and aggressive, multimodal treatment strategies, near-complete cure rates are possible, and many patients retain functional vision in at least 1 eye. However, in developing nations, where access to health care is limited, retinoblastoma can cause blindness and death.[6]

Among the mainstay treatments for retinoblastoma are intravenous chemotherapy (involving agents associated with significant toxicities), surgical enucleation, external beam radiotherapy, or all 3 options, potentially result in disfigurement and secondary malignancies. However, in recent years, an ongoing evolution has taken place, where treatment is being geared toward more targeted therapy and local medication delivery. Local delivery increases exposure to intraocular target areas, reduces overall systemic exposure and harmful late effects, and improves effectiveness and rates of tolerability. The introduction of intra-arterial and intravitreal chemotherapy has resulted in a change in treatment algorithms and improved outcomes, with their possibility of ocular salvage and maintenance of vision.[7]

Preclinical models that simulate human disease are needed for rare childhood cancers such as retinoblastoma because not enough patients with the disease exist for large-scale, multicenter clinical trials. Despite the lack of clinical trials, rates of survival and ocular preservation have improved.[7] In vitro studies and animal models remain instrumental in understanding biological mechanisms and assessing safety and effectiveness of the treatment options for this disease.[8–10] Examples of emerging therapies under investigation for retinoblastoma are alternative chemotherapeutic agents, molecularly targeted therapies, and novel drug-delivery systems.