Children with intraocular retinoblastoma who have access to modern medical care have a very good prognosis for survival (>95% in industrialized countries). The main risk factor associated with death is extraocular extension of the tumor, either directly through the sclera or, more commonly, by invasion of the optic nerve, especially to the surgically resected margin (see Chapter 11, Fig 11-46). Massive choroidal invasion (≥3 mm of invasion), extrascleral extension, or postlaminar optic nerve disease increase the risk that metastatic disease could develop. The highest risk of developing metastatic disease is in the setting of active tumor at the cut end of the optic nerve; this clinical situation requires adjuvant chemotherapy and radiation therapy. There is evidence that bilateral tumors may increase the risk of death because of the association with primary intracranial PNET.
Historically, children with extraocular retinoblastoma had a very poor prognosis for survival. However, in a recent COG report, the authors demonstrated that intensive multimodal therapies—including high-dose chemotherapy, radiation, and bone marrow transplantation—have enabled improved efficacy for curing patients with regional extraocular retinoblastoma (87% event-free survival [EFS] at 36 months) and metastatic retinoblastoma not involving the CNS (79% EFS at 36 months), while rates for patients with CNS disease continue to be dismal (8% EFS at 36 months).
Children who survive bilateral retinoblastoma have an increased incidence of a second-primary nonocular malignancy later in life. The mean latency for tumor development of a second tumor is approximately 9 years from management of the primary retinoblastoma. A patient with a germline RB1 mutation has an approximately 0.5%–1% incidence of second-primary tumor development per year of life; thus, the risk exceeds 25% at 50 years of age. This risk is elevated further in patients who were treated with EBRT. The most common type of second-primary cancer in these patients is osteosarcoma (also called osteogenic sarcoma). Other relatively common second malignancies include soft-tissue sarcomas, cutaneous melanoma, PNETs, other brain tumors, and primitive unclassifiable tumors (Table 19-4).
Table 19-4 Second-Primary Malignant Neoplasms in Retinoblastoma Survivors
Up to 20% of patients with bilateral retinoblastoma treated with chemotherapy will present with a second nonocular tumor within 20 years, and in up to 40% of those who were irradiated, a second or third nonocular tumor will develop. The 5-year survival rate in patients with sarcomas after retinoblastoma treatment is less than 50%. It is recommended that patients with germline RB1 mutations adhere to lifelong risk-modification practices, such as not smoking, avoiding unnecessary radiation exposure, and applying sunscreen. An international consensus panel convened by the American Association of Cancer Research recently gave recommendations for second-primary tumor surveillance in hereditary retinoblastoma; these include an annual physical examination, with an assessment of the skin to identify second-primary skin cancers, as well as education regarding the signs and symptoms of bone and soft-tissue sarcomas. Although it may be feasible to conduct annual whole-body MRI procedures on patients with RB1 germline mutations beginning at age 8–10 years (when general anesthesia would no longer be required), there is no consensus on the use of whole-body imaging as a surveillance tool. Effective screening strategies for second-primary nonocular cancers in this population is an area of active research.
Dunkel IJ, Krailo MD, Chantada GL, et al. Intensive multi-modality therapy for extra-ocular retinoblastoma (RB): a Children’s Oncology Group (COG) trial (ARET0321). J Clin Oncol. 2017;35(15 Suppl):10506–10506.
Kamihara J, Bourdeaut F, Foulkes WD, et al. Retinoblastoma and neuroblastoma predisposition and surveillance. Clin Cancer Res. 2017;23(13):e98–e106.
Excerpted from BCSC 2020-2021 series: Section 4 - Ophthalmic Pathology and Intraocular Tumors. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.