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Retinoblastoma Treatment (PDQ®)

Health Professional Version
Last Modified: 12/06/2013

Stage Information

Intraocular
Extraocular
Staging Systems
        AJCC Staging System
        International Retinoblastoma Staging System
Grouping Systems
        Reese-Ellsworth Classification for Intraocular Tumors
        International Classification of Retinoblastoma

Although there are several staging systems available for retinoblastoma,[1] for the purpose of treatment, retinoblastoma is categorized into intraocular and extraocular disease. Overall assessment of retinoblastoma extension is documented by staging systems; the intraocular extension, which is relevant for ocular salvage, is documented by grouping systems.

Intraocular

Intraocular retinoblastoma is localized to the eye and may be confined to the retina or may extend to involve other structures such as the choroid, ciliary body, anterior chamber, and optic nerve head. Intraocular retinoblastoma, however, does not extend beyond the eye into the tissues around the eye or to other parts of the body.

Extraocular

Extraocular (metastatic) retinoblastoma has extended beyond the eye. It may be confined to the tissues around the eye (orbital retinoblastoma), or it may have spread to the central nervous system, bone marrow, or lymph nodes (metastatic retinoblastoma).

Staging Systems

AJCC Staging System

Several staging systems have been proposed over the years. The AJCC clinical and pathological classifications represent a consensus opinion around which a common language is used.

Clinical classification system

Table 1. Primary Tumor (T)a
aReprinted with permission from AJCC: Retinoblastoma. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 562–63.
TXPrimary tumor cannot be assessed.
T0No evidence of primary tumor.
T1Tumors no more than 2/3 the volume of the eye with no vitreous or subretinal seeding.
T1aNo tumor in the either eye is greater than 3 mm in largest dimension or located closer than 1.5 mm to the optic nerve or fovea.
T1bAt least one tumor is greater than 3 mm in largest dimension or located closer than 1.5 mm to the optic nerve or fovea. No retinal detachment or subretinal fluid beyond 5 mm from above the base of the tumor.
T1cAt least one tumor is greater than 3 mm in largest dimension or located closer than 1.5 mm to the optic nerve or fovea, with retinal detachment or subretinal fluid beyond 5 mm from the base of the tumor.
T2Tumors no more than 2/3 the volume of the eye with vitreous or subretinal seeding. Can have retinal detachment.
T2aFocal vitreous and/or subretinal seeding of fine aggregates of tumor cells is present, but no large clumps or "snowballs" of tumor cells.
T2bMassive vitreous and/or subretinal seeding is present, defined as diffuse clumps or "snowballs" of tumor cells.
T3Severe intraocular disease.
T3aTumor fills more than 2/3 of the eye.
T3bOne or more complications present, which may include tumor-associated neovascular or angle closure glaucoma, tumor extension into the anterior segment, hyphema, vitreous hemorrhage, or orbital cellulitis.
T4Extraocular disease detected by imaging studies.
T4aInvasion of optic nerve.
T4bInvasion of the orbit.
T4cIntracranial extension not past chiasm.
T4dIntracranial extension past chiasm.

Table 2. Regional Lymph Nodes (N)a
aReprinted with permission from AJCC: Retinoblastoma. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 562–63.
NXRegional lymph nodes cannot be assessed.
N0No regional lymph node involvement.
N1Regional lymph node involvement (preauricular, cervical, submandibular).
N2Distant lymph node involvement.

Table 3. Metastasis (M)a
M0No metastasis.
M1Systemic metastasis.
M1aSingle lesion to sites other than CNS.
M1bMultiple lesions to sites other than CNS.
M1cPrechiasmatic CNS lesion(s).
M1dPostchiasmatic CNS lesion(s).
M1eLeptomeningeal and/or CSF involvement.

CNS = central nervous system; CSF = cerebrospinal fluid.
aReprinted with permission from AJCC: Retinoblastoma. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 562–63.

Pathologic classification system

Table 4. Primary Tumor (pT)a
aReprinted with permission from AJCC: Retinoblastoma. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 562–63.
pTxPrimary tumor cannot be assessed.
pT0No evidence of primary tumor.
pT1Tumor confined to eye with no optic nerve or choroidal invasion.
pT2Tumor with minimal optic nerve and/or choroidal invasion.
pT2aTumor superficially invades optic nerve head but does not extend past lamina cribrosa or tumor exhibits focal choroidal invasion.
pT2bTumor superficially invades optic nerve head but does not extend past lamina cribrosa and exhibits focal choroidal invasion.
pT3Tumor with significant optic nerve and/or choroidal invasion.
pT3aTumor invades optic nerve past lamina cribrosa but not to surgical resection line or tumor exhibits massive choroidal invasion.
pT3bTumor invades optic nerve past lamina cribrosa but not to surgical resection line and exhibits massive choroidal invasion.
pT4Tumor invades optic nerve to resection line or exhibits extra-ocular extension elsewhere.
pT4aTumor invades optic nerve to resection line but no extra-ocular extension identified.
pT4bTumor invades optic nerve to resection line and extra-ocular extension identified.

Table 5. Regional Lymph Nodes (pN)a
aReprinted with permission from AJCC: Retinoblastoma. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 562–63.
pNXRegional lymph nodes cannot be assessed.
pN0No regional lymph node involvement.
pN1Regional lymph node involvement (preauricular, cervical).
N2Distant lymph node involvement.

Table 6. Metastasis (pM)a
cM0No metastasis.
pM1Metastasis to sites other than CNS.
pM1aSingle lesion.
pM1bMultiple lesions.
pM1cCNS metastasis.
pM1dDiscrete mass(es) without leptomeningeal and/or CSF involvement.
pM1eLeptomeningeal and/or CSF involvement.

CNS = central nervous system; CSF = cerebrospinal fluid.
aReprinted with permission from AJCC: Retinoblastoma. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 562–63.

International Retinoblastoma Staging System

A simplified staging system, the International Retinoblastoma Staging System, has been proposed by an international consortium of ophthalmologists and pediatric oncologists.[2]

Table 7. International Retinoblastoma Staging System
Stage Description 
CNS = central nervous system; CSF = cerebrospinal fluid.
Stage 0Eye has not been enucleated and no dissemination of disease (refer to the International Classification of Retinoblastoma section of this summary for more information).
Stage IEye enucleated, completely resected histologically
Stage IIEye enucleated, microscopic residual tumor
Stage IIIRegional extensiona. Overt orbital disease
b. Preauricular or cervical lymph node extension
Stage IVMetastatic diseasea. Hematogenous metastasis (without CNS involvement)
1. Single lesion
2. Multiple lesions
b. CNS extension (with or without any other site of regional or metastatic disease)
1. Prechiasmatic lesion
2. CNS mass
3. Leptomeningeal and CSF disease

Grouping Systems

Grouping systems are relevant for assessment of intraocular disease extension and are helpful predictors of ocular salvage.

Reese-Ellsworth Classification for Intraocular Tumors

Reese and Ellsworth developed a classification system for intraocular retinoblastoma that has been shown to have prognostic significance for maintenance of sight and control of local disease at a time when surgery and external-beam radiation therapy (EBRT) were the primary treatment options.

Group I: very favorable for maintenance of sight

  1. Solitary tumor, smaller than 4 disc diameters (DD), at or behind the equator.
  2. Multiple tumors, none larger than 4 DD, all at or behind the equator.

Group II: favorable for maintenance of sight

  1. Solitary tumor, 4 to 10 DD at or behind the equator.
  2. Multiple tumors, 4 to 10 DD behind the equator.

Group III: possible for maintenance of sight

  1. Any lesion anterior to the equator.
  2. Solitary tumor, larger than 10 DD behind the equator.

Group IV: unfavorable for maintenance of sight

  1. Multiple tumors, some larger than 10 DD.
  2. Any lesion extending anteriorly to the ora serrata.

Group V: very unfavorable for maintenance of sight

  1. Massive tumors involving more than one half of the retina.
  2. Vitreous seeding.
International Classification of Retinoblastoma

There is a new grouping system for retinoblastoma, which may offer greater precision in stratifying risk for newer therapies. The International Classification of Retinoblastoma that is used in the current Children’s Oncology Group treatment studies and in some institutional studies has been shown to assist in predicting those who are likely to be cured without the need for enucleation or EBRT.[3-6] The International Classification of Retinoblastoma was able to predict high-risk histopathology in a study of over 500 patients with retinoblastoma. Histopathologic evidence of high-risk disease was noted in 17% of Group D and 24% of Group E eyes in this study. Such predication can be helpful in counseling parents regarding the need for postoperative systemic therapy.[7]

  • Group A: Small intraretinal tumors away from foveola and disc.
    • All tumors are 3 mm or smaller in greatest dimension, confined to the retina and
    • All tumors are located further than 3 mm from the foveola and 1.5 mm from the optic disc.

  • Group B: All remaining discrete tumors confined to the retina.
    • All other tumors confined to the retina not in Group A.
    • Tumor-associated subretinal fluid less than 3 mm from the tumor with no subretinal seeding.

  • Group C: Discrete local disease with minimal subretinal or vitreous seeding.
    • Tumor(s) are discrete.
    • Subretinal fluid, present or past, without seeding involving up to one-fourth of the retina.
    • Local fine vitreous seeding may be present close to discrete tumor.
    • Local subretinal seeding less than 3 mm (2 DD) from the tumor.

  • Group D: Diffuse disease with significant vitreous or subretinal seeding.
    • Tumor(s) may be massive or diffuse.
    • Subretinal fluid present or past without seeding, involving up to total retinal detachment.
    • Diffuse or massive vitreous disease may include “greasy” seeds or avascular tumor masses.
    • Diffuse subretinal seeding may include subretinal plaques or tumor nodules.

  • Group E: Presence of any one or more of the following poor prognosis features.
    • Tumor touching the lens.
    • Tumor anterior to anterior vitreous face involving ciliary body or anterior segment.
    • Diffuse infiltrating retinoblastoma.
    • Neovascular glaucoma.
    • Opaque media from hemorrhage.
    • Tumor necrosis with aseptic orbital cellulites.
    • Phthisis bulbi.

References
  1. Chantada GL, Sampor C, Bosaleh A, et al.: Comparison of staging systems for extraocular retinoblastoma: analysis of 533 patients. JAMA Ophthalmol 131 (9): 1127-34, 2013.  [PUBMED Abstract]

  2. Chantada G, Doz F, Antoneli CB, et al.: A proposal for an international retinoblastoma staging system. Pediatr Blood Cancer 47 (6): 801-5, 2006.  [PUBMED Abstract]

  3. Murphree L: Staging and grouping of retinoblastoma. In: Singh A, Damato B: Clinical Ophthalmic Oncology. Philadelphia, Pa: Saunders Elsevier, 2007, pp 422-7. 

  4. Zage PE, Reitman AJ, Seshadri R, et al.: Outcomes of a two-drug chemotherapy regimen for intraocular retinoblastoma. Pediatr Blood Cancer 50 (3): 567-72, 2008.  [PUBMED Abstract]

  5. Shields CL, Mashayekhi A, Au AK, et al.: The International Classification of Retinoblastoma predicts chemoreduction success. Ophthalmology 113 (12): 2276-80, 2006.  [PUBMED Abstract]

  6. Novetsky DE, Abramson DH, Kim JW, et al.: Published international classification of retinoblastoma (ICRB) definitions contain inconsistencies--an analysis of impact. Ophthalmic Genet 30 (1): 40-4, 2009.  [PUBMED Abstract]

  7. Kaliki S, Shields CL, Rojanaporn D, et al.: High-risk retinoblastoma based on international classification of retinoblastoma: analysis of 519 enucleated eyes. Ophthalmology 120 (5): 997-1003, 2013.  [PUBMED Abstract]