Standard treatment options
Because unilateral disease is usually massive and there is often no expectation that useful vision can be preserved, up-front surgery (enucleation) is usually recommended. Careful examination of the enucleated specimen by an experienced pathologist is necessary to determine whether high-risk features for metastatic disease are present. These features include anterior chamber seeding, choroidal involvement, tumor beyond the lamina cribrosa, or scleral and extrascleral extension.[40,41,42] Systemic adjuvant therapy with vincristine, doxorubicin, and cyclophosphamide or with vincristine, carboplatin, and etoposide has been used in patients with certain high-risk features assessed by pathologic review after enucleation to prevent the development of metastatic disease,[43,44,45,46]; [Level of evidence: 2A] with the suggestion of success compared with historical controls.[Level of evidence: 3iiDiii]
Patients with unilateral disease may also be offered chemotherapy and aggressive focal treatments in an attempt to save the eye and preserve vision.[1,49,50] Ocular salvage rates correlate with intraocular stage. In selected children with unilateral disease, R-E Group correlated with successful chemoreduction: 11% of children classified as having R-E Group II or III disease; 60% of children having R-E Group IV disease; and 100% of children having R-E Group V disease required enucleation or EBRT within 5 years of treatment. Caution must be exerted with extended chemotherapy and delayed enucleation when tumor control does not appear to be possible. Pre-enucleation chemotherapy for eyes with advanced intraocular disease may result in downstaging and underestimate the pathological evidence of extraretinal and extraocular disease, thus, increasing the risk of dissemination.
Pilot studies have evaluated the delivery of chemotherapy via ophthalmic artery cannulation as initial treatment for advanced unilateral and bilateral intraocular retinoblastoma. In the setting of a multidisciplinary, state-of-the-art center, intra-arterial chemotherapy may result in ocular salvage rates in excess of 80% for patients with advanced intraocular unilateral retinoblastoma.[31,35][Level of evidence: 3iiiDii]; [Level of evidence: 3iiiDiv]
Because a proportion of children who present with unilateral retinoblastoma will eventually develop disease in the opposite eye, it is very important that children with unilateral retinoblastoma receive periodic examinations of the unaffected eye, regardless of the treatment they received. Asynchronous bilateral disease occurs most frequently in patients with affected parents and in children diagnosed during the first months of life. Pre-enucleation magnetic resonance imaging has low sensitivity and specificity for the detection of high-risk pathology. As discussed, genetic counseling and testing at the time of diagnosis is the key to defining risk and planning follow-up.
The management of bilateral disease depends on the extent of the disease in each eye. Systemic therapy should be chosen based on the eye with more extensive disease. Treatment modality options described for unilateral disease may be applied to one or both affected eyes in patients with bilateral disease.