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Retinoblastoma

An eye cancer of infants caused by loss of the RB1 gene, the first tumour-suppressor gene ever found. In rich countries almost every child survives and most eyes are saved by chemotherapy delivered through the eye's artery; in poor countries many children still die because it is found too late.

Retinoblastoma arises from biallelic loss of RB1 in developing retinal cells (Knudson's two-hit hypothesis, 1971; RB1 cloned 1986), or rarely from MYCN amplification with intact RB1. Heritable disease (~40%, germline RB1) is usually bilateral and multifocal, presents earlier, and carries lifelong risk of second cancers (osteosarcoma, melanoma, sarcomas), especially after radiation. Leukocoria and strabismus are the presenting signs; diagnosis is clinical and by imaging (biopsy is avoided), and staging uses the International Intraocular Retinoblastoma Classification (groups A-E) and the TNMH system.

Treatment aims first at life, then at eye and vision. Advanced unilateral eyes (group E) are enucleated with pathologic high-risk features guiding adjuvant chemotherapy; salvageable eyes receive intra-arterial melphalan via the ophthalmic artery (Abramson, 2008), systemic chemoreduction (carboplatin, etoposide, vincristine) with focal laser/cryotherapy, and intravitreal melphalan for vitreous seeds. External-beam radiation is avoided in germline carriers. Extraocular and metastatic disease is treated with intensive chemotherapy and autologous stem-cell rescue; trilateral disease (pineal) is often fatal. Aqueous-humour cell-free DNA (2017) is the first liquid biopsy for a tumour that cannot be biopsied. Genetic counselling and screening of siblings and offspring are integral.

State of the art today

  • Intra-arterial chemotherapy saves eyes that would have been removed, with globe salvage ~70-90% in group D and few systemic effects.
  • Radiation has been almost eliminated because of second cancers in RB1 carriers.
  • Aqueous-humour cfDNA gives molecular information without biopsy.
Show survival figures (1)

Averages across everyone diagnosed, often years ago. Your stage, subtype, age, fitness and the treatment you receive matter more than the average, and the numbers are improving quickly.

  • The gap is global: >90% survival where diagnosis is early, versus death from orbital and metastatic disease where it is not (Global Retinoblastoma Study, 2020).
Who it affects
Show survival figures (1)

Averages across everyone diagnosed, often years ago. Your stage, subtype, age, fitness and the treatment you receive matter more than the average, and the numbers are improving quickly.

  • About 1 in 16,000-18,000 live births (~8,000 children per year worldwide); survival >95% in high-income countries but 30-60% in low-income countries where most cases occur.

Where the cases are

Cases by country · GLOBOCAN 2022
All countries →

No country-level case numbers. This cancer is not mapped to a GLOBOCAN site.

Standard of care

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Advanced unilateral (group E, no vision potential)

Primary enucleation with long optic nerve segment; adjuvant chemotherapy (VEC) for high-risk pathology; orbital implant.

NCI PDQ; ABS/ISOO consensus
VincristineEtoposideCarboplatin
Eye-salvage (groups B-D, bilateral)

Intra-arterial melphalan (± topotecan, carboplatin) via ophthalmic artery, or systemic chemoreduction (vincristine, etoposide, carboplatin) with consolidating laser, cryotherapy or plaque brachytherapy; intravitreal melphalan for vitreous seeds.

NCI PDQ
Melphalan (including hepatic delivery system)CarboplatinEtoposideVincristineTopotecanBrachytherapy
Extraocular / metastatic

Intensive multi-agent chemotherapy with autologous stem-cell rescue; radiotherapy to orbit; CNS disease has poor prognosis.

CyclophosphamideCarboplatinEtoposideAutologous stem cell transplant (high-dose therapy)IMRT / IGRT (modern external beam)
Surveillance and genetics

Serial examinations under anaesthesia until ~7 years; germline RB1 testing; screening of at-risk relatives from birth; lifelong second-cancer awareness in carriers.

Germline (hereditary) testing

Subtypes & biomarkers

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Subtypes
  • Heritable (germline RB1; usually bilateral)
  • Non-heritable unilateral (somatic RB1)
  • MYCN-amplified RB1-wild-type (infants, aggressive)
  • Trilateral retinoblastoma (with pineoblastoma)
  • Retinoma (benign precursor)
Biomarkers clinicians test

Target prevalence in this cancer

History

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  1. 1809Wardrop recommends enucleation for 'fungus haematodes'

    First curative approach.

  2. 1971Knudson's two-hit hypothesis

    Statistical analysis of hereditary vs sporadic retinoblastoma predicts tumour-suppressor genes.

  3. 1986RB1 cloned (Friend, Weinberg, Dryja)

    The first tumour-suppressor gene identified.

    TP53
  4. 1996Systemic chemoreduction with focal therapy replaces radiation (Shields, Gallie)
    Carboplatin
  5. 2008Intra-arterial melphalan via ophthalmic artery (Abramson)
    Melphalan (including hepatic delivery system)
  6. 2012Intravitreal melphalan for vitreous seeds (Munier)
    Melphalan (including hepatic delivery system)
  7. 2017Aqueous humour as liquid biopsy (Berry)
    Liquid biopsy (ctDNA)
  8. 2020Global Retinoblastoma Study: survival tied to national income (JAMA Oncol)

Pipeline

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Not mapped hereAlkylating agent (nitrogen mustard)
Melphalan (including hepatic delivery system) · Alkeran / Evomela / Hepzato Kit
Liquid biopsy (ctDNA)

Open problems

  • Late diagnosis and death in low-income countries; paediatric ophthalmology access.
  • Second primary cancers in RB1 carriers across life.
  • Vision outcomes after eye salvage.
  • Metastatic and CNS disease.

Trials

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Recruiting now (live from ClinicalTrials.gov)

Recruiting trials near you · live from ClinicalTrials.gov
Retinoblastoma
condition: Retinoblastoma
Open on ClinicalTrials.gov →

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Expert centres

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Where the expertise is

Centres linked to this cancer in OnCo

Seeking a second opinion: ask your oncologist for a referral to a high-volume centre; most accept records and pathology by mail or telehealth. In the US, use the NCI's Find a Cancer Center tool or the nonprofit Cancer Commons, which navigates options for advanced cancers at no cost.

Questions to ask

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Bring to your appointment

Questions to ask your oncologist about Retinoblastoma

Generated from this cancer's standard of care, biomarkers, and pipeline · 16 questions

Newly diagnosed

  1. What is my exact diagnosis, stage, and grade, and which tests established them?
    Why: Everything else follows from an accurate stage and subtype.
  2. Which biomarkers have been tested on my tumour (for example Germline RB1 testing, IIRC group A-E and TNMH stage, High-risk pathology after enucleation, Aqueous humour cfDNA, MYCN amplification), and what were the results?
    Why: These results decide eligibility for targeted therapy, immunotherapy, and trials.
  3. Which subtype is my cancer, and does that change the recommended treatment?
    Why: Recognised subtypes for this cancer include Heritable, Non-heritable unilateral, MYCN-amplified RB1-wild-type.
  4. Is germline (inherited) genetic testing recommended for me or my family?
    Why: Inherited variants can change treatment and matter for relatives.

Advanced unilateral (group E, no vision potential)

  1. For my situation (advanced unilateral (group e, no vision potential)), which of the standard options do you recommend and why?
    Why: Guideline options include: Primary enucleation with long optic nerve segment; adjuvant chemotherapy (VEC) for high-risk pathology; orbital implant.
  2. Am I a candidate for Vincristine, Etoposide, Carboplatin, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.

Eye-salvage (groups B-D, bilateral)

  1. For my situation (eye-salvage (groups b-d, bilateral)), which of the standard options do you recommend and why?
    Why: Guideline options include: Intra-arterial melphalan (± topotecan, carboplatin) via ophthalmic artery, or systemic chemoreduction (vincristine, etoposide, carboplatin) with consolidating laser, cryotherapy or plaque brachytherapy; intravitreal melphalan for vitreous seeds.
  2. Am I a candidate for Melphalan (including hepatic delivery system), Carboplatin, Etoposide or related drugs, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.

Extraocular / metastatic

  1. For my situation (extraocular / metastatic), which of the standard options do you recommend and why?
    Why: Guideline options include: Intensive multi-agent chemotherapy with autologous stem-cell rescue; radiotherapy to orbit; CNS disease has poor prognosis.
  2. Am I a candidate for Cyclophosphamide, Carboplatin, Etoposide, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.

Surveillance and genetics

  1. For my situation (surveillance and genetics), which of the standard options do you recommend and why?
    Why: Guideline options include: Serial examinations under anaesthesia until ~7 years; germline RB1 testing; screening of at-risk relatives from birth; lifelong second-cancer awareness in carriers.

Any stage

  1. Are there clinical trials I could join, for example of Melphalan (including hepatic delivery system), Liquid biopsy (ctDNA)?
    Why: Trials are how the next standard of care is set; asking early keeps options open.
  2. Would a second opinion at a high-volume centre change anything, and can you help arrange it?
    Why: Rare or high-stakes decisions benefit from a centre that treats many similar patients.
  3. What supportive care (symptom control, nutrition, exercise, mental health, financial help) is available from the start?
    Why: Supportive care improves quality of life and helps patients complete treatment.
  4. I read that “Late diagnosis and death in low-income countries; paediatric ophthalmology access”. How does that affect my plan?
    Why: Open problems are where trials and second opinions matter most.
  5. I read that “Second primary cancers in RB1 carriers across life”. How does that affect my plan?
    Why: Open problems are where trials and second opinions matter most.

Print this page for your appointment (your browser's print command). These prompts are for discussion; your clinical team knows your case.

Everything relevant

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Direct links plus the targets, companies, and technologies of this cancer's products.

technologies

14
Allogeneic stem cell transplantationAutologous stem cell transplant (high-dose therapy)BrachytherapyCAR-T cell therapyCytotoxic chemotherapyGermline (hereditary) testingGlobal oncology and access in low- and middle-income countriesIMRT / IGRT (modern external beam)Isolated limb perfusion and infusionLiquid biopsy (ctDNA)MRIPercutaneous hepatic perfusion (chemosaturation)Platinum agentsTopoisomerase-I inhibitors (and ADC payloads)

targets

2
KMT2A (MLL) rearrangementTP53

drugs

6
ApprovedCytotoxic chemotherapy (platinum)
Carboplatin
Not mapped hereAlkylating agent (oxazaphosphorine prodrug)
Cyclophosphamide · Cytoxan / Endoxan
Not mapped hereTopoisomerase II inhibitor (podophyllotoxin derivative)
Etoposide · VePesid / Etopophos / Toposar
Not mapped hereAlkylating agent (nitrogen mustard)
Melphalan (including hepatic delivery system) · Alkeran / Evomela / Hepzato Kit
ApprovedCytotoxic (topoisomerase-I inhibitor)
Topotecan · Hycamtin
Not mapped hereVinca alkaloid (microtubule inhibitor)
Vincristine · Oncovin / Marqibo

institutions

4
Children's Oncology Group (COG)Fox Chase Cancer CenterMemorial Sloan Kettering Cancer CenterSt. Jude Children's Research Hospital

pathways

2
Drivers, passengers & the two-hit modelp53 / RB / cell-cycle checkpoint

terms

2
Germline vs somatic mutationsHereditary cancer syndromes

collections

1
Alex's Lemonade Stand Foundation (ALSF)

Latest papers

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Latest papers · live from Europe PMC
Open in Europe PMC

Query for this cancer: (TITLE:"Retinoblastoma" OR ABSTRACT:"Retinoblastoma") AND (treatment OR therapy OR trial OR survival OR diagnosis). Results are unfiltered search hits about Retinoblastoma, not a curated reading list.

Connected

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Pages like this

not linked directly; found by shared links

technologies

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Autologous stem cell transplant (high-dose therapy)BrachytherapyCytotoxic chemotherapyGermline (hereditary) testingGlobal oncology and access in low- and middle-income countriesIMRT / IGRT (modern external beam)Liquid biopsy (ctDNA)MRI

targets

1
TP53

drugs

6
ApprovedCytotoxic chemotherapy (platinum)
Carboplatin
Not mapped hereAlkylating agent (oxazaphosphorine prodrug)
Cyclophosphamide · Cytoxan / Endoxan
Not mapped hereTopoisomerase II inhibitor (podophyllotoxin derivative)
Etoposide · VePesid / Etopophos / Toposar
Not mapped hereAlkylating agent (nitrogen mustard)
Melphalan (including hepatic delivery system) · Alkeran / Evomela / Hepzato Kit
ApprovedCytotoxic (topoisomerase-I inhibitor)
Topotecan · Hycamtin
Not mapped hereVinca alkaloid (microtubule inhibitor)
Vincristine · Oncovin / Marqibo

institutions

4
Children's Oncology Group (COG)Fox Chase Cancer CenterMemorial Sloan Kettering Cancer CenterSt. Jude Children's Research Hospital

pathways

2
Drivers, passengers & the two-hit modelp53 / RB / cell-cycle checkpoint

terms

2
Germline vs somatic mutationsHereditary cancer syndromes

collections

1
Alex's Lemonade Stand Foundation (ALSF)