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Retinoblastoma Treatment (PDQ®)

Treatment Options for Unilateral and Bilateral Retinoblastoma

Standard Treatment Options for Unilateral Retinoblastoma

Standard treatment options for unilateral retinoblastoma include the following:

  1. Enucleation for large intraocular tumors, followed by risk-adapted chemotherapy when the eye cannot be saved.
  2. Conservative ocular salvage approaches when the eye and vision can be saved.
    • Chemoreduction with either of the following:
      • Systemic chemotherapy with subtenon chemotherapy.
      • Ophthalmic artery infusion chemotherapy.
    • Local treatments including cryotherapy, thermotherapy, and plaque radiation therapy.
    • External-beam radiation therapy (EBRT).

Enucleation followed by chemotherapy

Because unilateral disease is usually massive and often there is no expectation that useful vision can be preserved, up-front surgery (enucleation) is commonly performed. 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 the following:[1-5]

  • Anterior chamber seeding.
  • Massive choroidal involvement.
  • Tumor beyond the lamina cribrosa.
  • Scleral and extrascleral extension.

Pre-enucleation magnetic resonance imaging has low sensitivity and specificity for the detection of high-risk pathology.[6]

Systemic adjuvant therapy with vincristine, doxorubicin, and cyclophosphamide or with vincristine, carboplatin, and etoposide has been used to prevent the development of metastatic disease in patients with certain high-risk features assessed by pathologic review after enucleation.[3,7,8]; [9][Level of evidence: 2A]

Conservative ocular salvage approaches

Conservative ocular salvage approaches, such as chemotherapy and local-control treatments, may be offered in an attempt to save the eye and preserve vision.[10] Ocular salvage rates correlate with intraocular stage. In selected children with unilateral disease, the Reese-Ellsworth (R-E) Group was correlated with ocular outcomes. While the possibility of saving the eye without the use of EBRT was greater than 80% for children with R-E Group II or III disease, the ocular outcomes for children with R-E Group V eyes were poor, with less than 40% ocular salvage rates, even after the use of EBRT.[11]

Caution must be exerted with extended systemic chemotherapy administration and delayed enucleation when tumor control does not appear to be possible, particularly for Group E eyes. 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.[12]

The delivery of chemotherapy via ophthalmic artery cannulation as initial treatment for advanced unilateral retinoblastoma appears to be more effective than does systemic chemotherapy for chemoreduction. In the setting of a multidisciplinary state-of-the-art center, intra-arterial chemotherapy may result in ocular salvage rates greater than 80% for patients with advanced intraocular unilateral retinoblastoma.[13]; [14,15][Level of evidence: 3iiiDii]; [16][Level of evidence: 3iiiDiv]

Because a proportion of children who present with unilateral retinoblastoma will eventually develop disease in the opposite eye, these children undergo genetic counseling and testing and 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.

Standard Treatment Options for Bilateral Retinoblastoma

The management of bilateral disease depends on the extent of the disease in each eye. Systemic therapy is generally 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. Systemic or intra-arterial chemotherapy (chemoreduction) coupled with aggressive local treatments and very close monitoring is usually the treatment of choice; the goal is ocular and vision preservation and the delay or avoidance of EBRT and enucleation.

Standard treatment options for bilateral retinoblastoma include the following:

  1. Enucleation for large intraocular tumors, followed by risk-adapted chemotherapy when the eye and vision cannot be saved.
  2. Conservative ocular salvage approaches when the eye and vision can be saved.
    • Chemoreduction with either of the following:
      • Systemic chemotherapy with subtenon chemotherapy.
      • Ophthalmic artery infusion chemotherapy.
    • Local treatments including cryotherapy, thermotherapy, and plaque radiation therapy.
    • EBRT.

Intraocular tumor burden is usually asymmetric, and treatment is dictated by the most advanced eye. While up-front enucleation of an advanced eye and risk-adapted adjuvant chemotherapy may be required, a more conservative approach using primary chemoreduction with close follow-up for response and aggressive local treatment may be indicated. EBRT is now reserved for patients whose eyes do not respond adequately to primary systemic or intra-arterial chemotherapy and local consolidation.

A number of large centers have published trial results that used systemic chemotherapy in conjunction with aggressive local consolidation for patients with bilateral disease.[10,17-25] The backbone of the chemoreduction has generally been carboplatin, etoposide, and vincristine. Chemotherapy shrinks the tumors (chemoreduction), allowing greater efficacy of subsequent local therapy.[10] Treatment strategies often differ in terms of chemotherapy regimens and local control measures. Using this approach, the International Classification of Retinoblastoma grouping system has been proven to predict ocular salvage.[26,27]; [28][Level of evidence: 3iiDiv]

  • Groups A and B: Systemic chemotherapy in conjunction with local control have resulted in ocular salvage rates greater than 90% for early intraocular disease.[27-29]
  • Groups C and D: Ocular salvage rates using this approach are 70% to 90% for Group C eyes and 40% to 50% for Group D eyes.[27-29] However, for patients with more advanced intraocular disease (typically Group D eyes), EBRT is frequently required for ocular salvage.[28]; [29][Level of evidence: 3iiDiii]

    For patients with large intraocular tumor burden with subretinal or vitreous seeds (Groups D eyes), the administration of higher doses of carboplatin, coupled with subtenon carboplatin, and the addition of lower doses of EBRT (36 Gy) for patients with persistent disease has been explored. Using this intensive approach, eye survival may approach a rate of 70% at 60 months.[30][Level of evidence: 2Div]

  • Group E: The treatment for Group E eyes is up-front enucleation. The use of prolonged systemic chemotherapy for Group E eyes to avoid or delay enucleation has been associated with lower disease-specific survival.[12][Level of evidence: 3iiiB]

Delivery of chemotherapy via ophthalmic artery cannulation has also been shown to be feasible and effective in patients with newly diagnosed bilateral disease as tandem administration and in the salvage setting.[14,15,31,32][Level of evidence: 3iiDii] Bilateral administrations increase the risk of systemic toxicity caused by melphalan exposure.[33] In these circumstances, intra-arterial chemotherapy with single-agent carboplatin may be used to treat the less-advanced eye during the tandem procedure.[34] These treatments should only be performed in an experienced center with a state-of-the-art treatment infrastructure and a dedicated multidisciplinary team.

Cavitary Retinoblastoma

In patients with cavitary retinoblastoma, minimal visual response is seen after intravenous chemotherapy and/or intra-arterial chemotherapy. Despite the blunted clinical response, cavitary retinoblastoma has a favorable long-term outcome with stable tumor regression and globe salvage. Aggressive or prolonged chemotherapy or adjunctive therapies are generally not necessary. In a retrospective series of 26 cavitary retinoblastomas that were treated with intravenous chemoreduction and/or intra-arterial chemotherapy, the mean reduction in tumor base was 22%, and the mean reduction in tumor thickness was 29%. Despite minimal reduction, tumor recurrence was noted in only one eye, globe salvage was achieved in 22 eyes, and there were no cases of metastasis or death during 49 months (range, 6–189 months) of follow-up.[35]

Treatment Options Under Clinical Evaluation for Intraocular Retinoblastoma

Studies are planned for a variety of patient groups. The International Classification of Retinoblastoma is being utilized for these trials.

The following is an example of a national and/or institutional clinical trial that is currently being conducted. Information about ongoing clinical trials is available from the NCI Web site.

  • ARET12P1 (NCT02097134) (Intra-arterial Melphalan in Treating Younger Patients With Unilateral Retinoblastoma): This pilot clinical trial is studying whether unilateral Group D retinoblastoma, or retinoblastoma affecting one eye that has spread to the vitreous fluid, can be treated with intra-arterial injection. This may provide children with unilateral retinoblastoma a lower chance of needing surgery to remove the eye and reduce the severity of treatment side effects.

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with intraocular retinoblastoma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.


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  • Updated: February 2, 2015