DISCUSSION
Adherence to treatment for retinoblastoma was low in the Ivory Coast and the DRC with 22.3% refusal of chemotherapy, 45.1% refusal of enucleation, 27.4% abandonment of treatment, and 18.3 % loss to follow-up after treatment.
The global rate of refusal and abandonment of treatment for childhood cancers is recorded; however, results are distributed unevenly with less than 10% of cases in high-income countries5. In contrast, it can reach up to more than 90% in low-income countries5 where the refusal of enucleation can go up to 100% of cases7. Ye described 35.8% of chemotherapy refusal cases in China16, while Malliptana reported 0.8% of refusal cases in a series in Canada17.
There has also been a regional disparity in the rate of loss of follow-up worldwide: 13 to 16% in some countries with limited resources16,18, 18 to 36% in some African countries19,20, and lower rates in developed European countries such as Italy where 5.6% of patients were lost to follow-up during treatment for retinoblastoma by intra-arterial injection of melphalan21.
Our chemotherapy refusal rate matches other low- and middle-income countries. The financial difficulties, which are the main causes of the refusal of chemotherapy in our environment, could reflect the inaccessibility to medical care in most French-speaking sub-Saharan African countries22,23. Enucleation refusal rates like ours have been described in sub-Saharan Africa, where a large proportion of deaths related to enucleation refusal have been noted in the absence of care improvement programs24,25. The most frequent causes are belief in traditional treatments or the fatality of cancer as well as fear of the aesthetic outcomes resulting from surgery, and fear of stigmatization7,26. Despite the similarity to other low or middle-income countries, our results had the distinction of having financial difficulties as the second cause after the fear of infirmity.
Bilaterality was a factor that influenced the refusal of enucleation in our study, which was similar to the findings of a series in India27. In our countries where conservative treatment is not well developed yet, the fear of bilateral enucleation could explain this parental attitude.
In this study, which is the first of its kind in French-speaking sub-Saharan Africa, we found that the absence of secure management of medical care, the unmarried status of parents, the low level of education, and the low qualification of the parents’ professions were determinants and predictors of the refusal and abandonment of treatment.
Financial difficulties are the main causes of abandonment of treatment described in other countries, particularly in Asia27-30. Other causes include the fear of enucleation27,28, and difficulties related to travel for families who live far from care centers29,30. In Africa, financial difficulties and the unavailability of drugs are reported as reasons for abandoning treatment3 due to poor funding through social security and health insurance systems. In principle, we reported similar causes, and fear of side effects (including fear of the consequences of enucleation) was among the causes of discontinuation of treatment. Moreover, difficulties in traveling to the specialized center and the unavailability of medication may be the consequences of financial difficulties.
Consultation with the traditional healer is a particularity that we found to be a predictor of the abandonment of the treatment. This could be explained by the fact that those who resort first to this category of health professionals believe less in the effectiveness of modern treatment. However, we do not have a particular explanation for the influence of consulting other health professionals (nurse, general practitioner, pediatrician) on the refusal or abandonment of treatment.
Furthermore, we had many more dropouts when the treatment started with chemotherapy: this may be due to the fact that the parents dropped out of the treatment at the time of enucleation; whereas the opposite was observed in Latin America, where neo-adjuvant chemotherapy made it possible to accept enucleation in a certain number of children3,31. Perhaps our families were less prepared for enucleation, even when chemotherapy treatment was started.
Ultimately, the financial difficulties of the parents and their understanding of the disease and its treatment are major determinants of refusal and abandonment of treatment. Psychosocial and financial support programs for families (with better communication on the ocular prosthesis, the prognosis, etc.) can improve adherence to treatment for childhood cancers and survival, as has been proven elsewhere32,33.
Survival linked to retinoblastoma varies greatly according to geographic location. In developed countries, survival is more than 97%34, with preservation of vision in at least one eye reaching 90% of cases2. However, in several African and Asian countries, the mortality rate varies between 40 and 70%35. Socioeconomic factors as well as the refusal and abandonment of treatment contribute to this high mortality3,35. The 56% 3-year survival rate found in our study is consistent with rates found in sub-Saharan African countries. Most of the patients who dropped out of treatment did so within the first 6 months. This matches the results of a study in East Africa where retinoblastoma-related survival was difficult to estimate because most children were lost to follow-up during the first year of treatment36.
Advanced forms of retinoblastoma are generally associated with low socioeconomic status37 which negatively influences (with refusal or abandonment of treatment) survival35, as observed in our study.
The median age at diagnosis is 14 months in high-income countries and 30.5 months in low-income countries37. Age was slightly higher in our study as was the number of cases with advanced forms of retinoblastoma. This may be explained by the association of advanced age with advanced forms of retinoblastoma37.
The sex ratio was approximately 1 in our study. Other studies reported that there is often a slight male predominance without any impact on the evolutionary forms or survival37,38. Nevertheless, studies from India occasionally report a predominance of the refusal or abandonment of treatment in females, which probably follows the cultural discrimination in favor of boys in the attention granted to medical care by parents27.
Siblings are not described as a factor affecting treatment adherence. However, the number of people per room in the house is involved in the calculation of certain indices of socioeconomic level, which influence treatment39. We can estimate that a large number of children per family is associated with a low socioeconomic level which would lead to difficulties in accessing medical care.
One limitation of our work was that we were unable to find all the information we wanted in the retrospective files despite the effort to complete them by telephone. However, this study has identified the main factors influencing adherence to treatment in our settings. This information could be better supplemented by a subsequent qualitative study.