Unique Challenges in the Management of Retinoblastoma in India – Need for Country-Specific Guidelines

Abstract

The management of retinoblastoma in the Indian subcontinent is riddled with unique challenges. Compared to Western countries, a significant proportion of children with retinoblastoma in India present with an advanced disease, and consequently, there is a relatively lower proportion of globe salvage and cure rates achieved. The international guidelines for the management of retinoblastoma are often not suited for addressing the varying stages of presentation of retinoblastoma in India and its specific socio-cultural context. The need for a comprehensive country-specific guideline, which incorporates updated recommendations as per latest available evidence, along with additional aspects specific for implementation in India, was felt. The recently published guidelines, developed by an expert committee constituted by Indian Council of Medical Research (ICMR), was a necessary step to address that need [1,2,3]. The guidelines were developed by robust review of literature, along with expert-consensus statements, wherever the available literature was unclear. The guidelines have applicability both in international as well as local context, especially for entire South East Asia and other low-middle income settings. Singh et al. succinctly summarized the differing epidemiology of retinoblastoma in India [1]. The article clearly brings out the delayed age of presentation in India compared to high-income countries, which in turn perhaps contributes to more advanced stage of presentation. Children in India often face multiple barriers to achieve diagnosis of malignancy and initiation of appropriate treatment [4]. The delay is often multi-factorial and may be linked to difficult healthcare resource access, inadequate available infrastructure as well as poor compliance to treatment. Sex-based disparity in favor of boys also contributes to treatment abandonment and consequently, inferior outcomes across childhood cancers in India [5]. Hence, ensuring socio-economic support and compliance during treatment forms an integral component of management of retinoblastoma in India. For management of intraocular retinoblastoma, in high-income settings, the emphasis is often more on intra-arterial therapy. However, the availability of expertise in intra-arterial therapy and its affordability is still limited across the country. Hence, intravenous chemotherapy with focal therapy has been emphasized as a reasonable and even preferable option for the management of intraocular retinoblastoma [3]. Similarly, the management of advanced and extra-ocular retinoblastoma has been elaborated in details in these guidelines, as they are commonly encountered in routine clinical practice in India, unlike that in Western countries, where familiarity and expertise in advanced retinoblastoma remains limited [2]. Children with advanced retinoblastoma where cure is not attainable, especially for those with central nervous system involvement, should be managed with palliative intent. These guidelines have judiciously suggested the use of oral metronomic therapies instead of intensive chemotherapy in such palliative settings, where the predominant aim is to improve the quality of life and reduce adverse effects. Quality of life should be accorded paramount importance for evaluating or selecting any therapy, especially in non-curative settings. The guidelines have also briefly touched upon the aspect of retinoblastoma survivorship and follow-up evaluation. The follow-up of retinoblastoma survivors need multi-disciplinary collaboration among oculoplastic surgeons, oncologists, psychologists, and pediatricians. A previous study on quality of life in retinoblastoma survivors has demonstrated impaired quality of life, especially in emotional domain [6]. This suggests that comprehensive psychological evaluation and quality of life assessment should also form a part of survivorship care in retinoblastoma. The guidelines also put forward multiple unanswered questions in the management of retinoblastoma. The role of high dose carboplatin to improve globe salvage in intraocular retinoblastoma was recently evaluated in a randomized controlled trial and it did not show any significant improvement in the proportion of globe salvage with the use of higher dose of carboplatin [7]. Yet, the trial was underpowered and hence, the current place of high-dose carboplatin in the management paradigm of retinoblastoma continues to be controversial. Similarly, the role of low-intensity therapies like metronomic therapies or alternative strategies like intrathecal therapies in intracranial involvement needs to be systematically studied with collaborative studies in India, where the burden of metastatic disease continues to remain high. The development of Indian Pediatric Oncology Group (InPOG) for spearheading collaborative research in various disease groups is a step in the right direction [8]. The guidelines did not address the potential areas of research and incorporation of traditional or alternative medications in the management of retinoblastoma. Traditional systems of medicine often have phytochemicals of significant anti-cancer properties, which warrant systematic study. There was a significant impetus for the clinical study of traditional medications during COVID-19 pandemic [9]. Recently, a screen of Chinese herbal medicines has identified xanthatin as an active agent, which specifically targets retinoblastoma cell lines and has also shown activity in in-vivo models [10]. Similarly, the Indian systems of medicine also have multiple herbal or other traditional compounds and encouraging their systematic evaluation may spearhead new drug development in the management of retinoblastoma. The recently published comprehensive guidelines on the management of retinoblastoma were a necessary step in the development of country-specific guidelines to address unique needs suited for India. It will form a valuable resource for practicing clinicians as well as for healthcare trainees. Similar guidelines for other malignancies which are pragmatic and incorporate practical needs of clinicians in the country should be envisaged and developed.