Risk of Under-Treatment and Over-Treatment
When a child has retinoblastoma, there may be a fine line between the right amount of treatment and effort to save eyes and sight, too much treatment of a dangerous eye, and not enough treatment to protect the child’s life. Two mothers share their children’s stories…
Retinoblastoma is Prone to Relapse
New tumour growth and relapse within the eye are common among children who have eye salvage treatment. More tumours may form, and old tumours may re-grow. Most children experience multiple, frequent relapses or new tumours over several years, and ocular oncologists familiar with retinoblastoma expect this.
The risk of further cancer activity within the eye depends on genetics and the type of retinoblastoma, stage of disease at diagnosis, and treatment history. Together, these factors guide appropriate follow up care when each course of treatment ends.
Life-threatening relapse outside the eye may occur when the child has advanced intraocular retinoblastoma. This risk is the same for children with unilateral and bilateral cancer. Relapse is more likely when treatment and follow-up are inconsistent and incomplete, or inappropriate for the stage of intraocular cancer.
Under-treatment and over-treatment can occur when the child’s therapy and/or follow-up care does not match their stage of cancer.
What Does Under-Treatment and Over-Treatment Mean?
The terms under-treatment and over-treatment are not clearly defined in childhood cancer care. However, generally within medical care, they mean the following:
Under-Treatment: Insufficient, or less than recommended therapy and surveillance for the stage of a medical condition, increasing the risk of sub-optimal outcomes.
Over-Treatment: intensive therapy and surveillance in which the potential side-effects and risks outweigh the potential benefits.
A child with retinoblastoma may experience both under-treatment of life-threatening cancer, and over-treatment of cancer within the eye. Imagine a child who receives eye-salvage therapy for unilateral advanced intraocular retinoblastoma that has already destroyed sight.
- Therapy may fail to treat cancer cells on the eye’s outer layers, increasing the risk of relapse outside the eye (under-treatment of the whole child).
- Physical and psychological effects of invasive eye-salvage therapy, and risk to the child’s life, may be greater than potential to save the eye with useful vision (over-treatment of the eye).
How Do We Define Advanced Intraocular Retinoblastoma?
Cancer is staged to predict how effective different treatments are to save the person’s life. In retinoblastoma, each eye is staged independently to indicate likelihood that a treatment can safely save the child’s eye, and achieve useful vision. Cancer stage for a bilaterally affected child is based on the worst affected eye, as an indicator of risk to the child’s life.
“Intraocular retinoblastoma” means the clinical exam and imaging results suggest cancer is contained in the eye.
“Extraocular retinoblastoma” means the results indicate cancer has escaped the eye – this is of course a more advanced situation.
Two systems are commonly used today to stage retinoblastoma: the International Intraocular Retinoblastoma Classification (IIRC Groups A to E) and the TNMH (Tumour, Node, Metastasis, and Heritability). TNMH stages cT1a to cT3 are broadly similar to IIRC A-E, with some distinct differences. WE C Hope provides a detailed explanation of both staging systems.
Advanced intraocular retinoblastoma refers to TNMH cT2b and cT3, and IIRC Groups D and E.
Parents, please make sure you know your child’s individual staging at diagnosis and each stage of treatment, and understand what it means. Doctors, please give this information whether or not a parent asks for it. Staging provides vital context to enable informed decision making and parent consent throughout the child’s care.
A visual progression of retinoblastoma through the TNMH Staging System.
Who is At Risk for Under-Treatment or Over-Treatment?
Every child with retinoblastoma faces a risk of under-treatment and/or over-treatment, but some factors significantly increase risk.
- Children receiving eye-salvage therapy for advanced intraocular retinoblastoma. Particularly eye-focused therapies such as intra-arterial chemotherapy and intra-vitreal chemotherapy, which do not reach cancer cells on the eye’s outer layers or beyond.
- Children who receive inconsistent or incomplete therapy and / or follow-up eye exams after therapy (whether eye salvage or enucleation). This is particularly common among families who move frequently, in developing countries, and international patients, when access specialist care is difficult.
- Children diagnosed with unilateral retinoblastoma who receive inadequate surveillance of the cancer-free eye, when they are known to have an RB1 mutation, or their genetic status and risk to the eye are unknown.
- Children after enucleation when eye pathology fails to identify and report high risk features. Often this may be due to the ‘masking’ effects of initial chemotherapy shrinking tumour within the eye, suggesting a falsely low risk of cancer beyond the eye, and ‘downgrading’ the pathology.
- Children after enucleation when post-surgery care fails to quickly address high-risk pathology.
- Infants treated with low-dose chemotherapy that may cause the cancer to become chemo-resistant.
- Children receiving eye-salvage therapy for severely advanced intraocular retinoblastoma (eye staged IIRC Group E or TNMH cT3).
- Children receiving eye-salvage therapy when there is remote chance of saving or recovering sight, particularly when the child has unilateral retinoblastoma and the other eye has good vision.
- Children who receive chemotherapy after enucleation because eye pathology is unavailable, delayed or incomplete. This is common in developing countries, where accurate, timely ocular pathology is often limited or absent.
- Children who receive chemotherapy after enucleation because the pathology report cannot be trusted due to the potential “masking” effects of pre-surgery therapy.
- Children with unilateral retinoblastoma who continue to have surveillance Exams Under Anaesthesia for their cancer-free eye, after genetic testing has established there is no or remote risk to that eye (MYCN mutation is identified, or the tumour’s RB1 mutation is not found in blood). This also applies to siblings of a diagnosed child, when genetic testing eliminates their risk.
What Are the Consequences of Under-Treatment and Over-Treatment?
For both the child and their family, there are many consequences of too little, or too much treatment. Below are the most critical considerations for each scenario.
- Unseen cancer cells continue to multiply, and may spread outside the eye.
- Eye-salvage therapy may appear to kill retinoblastoma within the eye, while failing to treat cancer threatening the child’s life.
- The child ultimately requires significantly more intensive and prolonged therapy than could have been achieved with appropriate medical care. This therapy is more expensive, with far higher costs to the physical and psychological wellbeing of both child and family.
- The potential to cure decreases significantly when retinoblastoma escapes the eye. Even with the most advanced therapies, the child may die.
- The child may experience many more invasive medical procedures, therapies, and hospitalizations than necessary.
- Long-term physical and psychological impacts of retinoblastoma may be increased with prolonged therapy, including increased risk of second primary cancers and non-cancer health issues.
- Practical, relational, psychological, and financial cost to the entire family are higher than necessary.
- Family members and medical professionals may be less able to acknowledge the need for enucleation after even one round of eye-salvage therapy, potentially delaying life-saving surgery.
- When a blind eye is saved, or enucleation is delayed by prolonged eye-salvage therapy, cosmetic appearance and prosthesis fit are often poorer than can be achieved with immediate enucleation.