Table 3.

Qualitative comparison of enucleation, IVC and IAC for unilateral retinoblastoma (Murphree IIRC Groups B, C, D).

	Enucleation	IVC and focal therapy	IAC and focal therapy
Treatment	Major muscles removed, optic nerve cut, eye removed; orbital volume reconstituted with implant; muscles sutured to gain motility of the artificial eye, held in place by the eyelids.	Chemotherapy (carboplatin, vincristine, and etoposide) is given intravenously, best through an implanted “port”, every 3-4 weeks; tumour response consolidated by focal therapy (laser and cryotherapy) every 1–4 months for 3 years.	Chemotherapy (melphalan, and/or carboplatin, and/or topotecan) infused via micro-catheter through femoral artery, near, or into the ophthalmic artery with radiographic confirmation; tumour response consolidated by focal therapy (laser and cryotherapy), every 1–4 months for 3 years.
Success rate to save eye (%)	0%	47% Group78 D; >90% Group B & C	45129 to 95130% Group78 D*; >90% Group B & C
Acute toxicity	Loss of eye; parental distress waiting for artificial eye fitting; transient bruising, swelling and headache	Hair loss; low white cell count; fevers require IV antibiotics and hospital admission; protective isolation at a time of social development; parental distress over prolonged treatment	Groin haematoma; transient low white cell count; potential carotid vascular spasm and stroke; vascular compromise of the ophthalmic artery, retinal artery, or choroidal vessels; headache
No. of Procedures	1 surgery	2–8 chemotherapy cycles every 3 weeks	2–8 treatments, every 4 weeks
No. of EUAs	1 (unless patients are RB1+/−)	>20 for consolidation and monitoring	>10 since only 30% need consolidation
Patient survival	>99%	>98%	high unless undetected high risk features
High risk pathology detected	Yes	No	No
Hidden metastases treated	No	Yes	No
Identification of tumour genetics	Yes	No	No
Duration of treatment	2 months (if not RB1+/−)	> 1 year	> 1 year
Invasive surgery	Loss of eye	1 central venous catheter	2–8 intracranial arterial canulations
Long term toxicity	Loss of eye	High tone hearing loss ~20% (Carboplatin); <1% AML (etoposide)	4% severe vascular choroidal toxicity; long term unknown vision risk
psychological harms	Possibly low self-esteem due to loss of the eye or artificial eye; distress of fitting and maintenance of artificial eye	Years of social isolation for treatments; delay physical, emotional, social development; long term separations of families; parental relationship breakdown; hospital-associated anxiety that hinders future medical care; post-traumatic stress disorder; Developmental Trauma Disorder; parental anxiety over illnesses; PTSD in parents or siblings; financial distress
Radiation	none	No Group78 D get EBRT; enucleation preferred	Fluoroscopy; No Group78 D to need EBRT
Socio-economic impact108	minimal	profound	very profound
Disease-specific mortality	≪1%	<1%	unknown
Resource	Anaesthesia; ophthalmic surgery, ocularist; artificial eye	Anaesthesia; retinoblastoma and oncology expertise; drugs; laser and cryotherapy equipment; imaging equipment; Child Life support;181 long term follow-up	Anaesthesia; retinoblastoma-specific interventional radiology and oncology expertise; drugs; laser and cryotherapy equipment; imaging equipment; Child Life support;181 long term follow-up
Long term follow-up	Minimal unless inherited	Every 2–6 months for 4 years after tumour control	Every 2–6 months for 4 years after tumour control
Availability:
Available in high income countries	Yes	Yes	Yes
Available in middle income countries	Yes	Yes	Limited
Available in low income countries	Yes	No	No

AML, acute myeloid leukaemia; EUA, examination under anaesthesia; IV, intravenous; IVC, intravenous chemotherapy; IAC, intra-arterial chemotherapy; * very wide range reflects different classifications and different follow-up durations.