Survival outcomes and globe salvage rates of retinoblastoma in India – A systematic review

Abstract

Purpose:

The World Health Organization (WHO) CURE-ALL initiative highlights retinoblastoma (RB) as an index cancer, prompting Indian centers to collaborate for better RB outcomes. The current study is a systematic review of published RB survival outcomes from India till date, thereby providing a crucial roadmap for ongoing efforts.

Methods:

The PubMed and Google Scholar databases were searched till April 2024. The reference lists of selected articles were also searched manually for additional studies. Non-Indian articles, multicentric studies, case reviews, duplicates, and studies not mentioning outcomes were excluded. Fifteen eligible studies were shortlisted for review.

Results:

The total number of patients was 4147. Median age at diagnosis was between 24–36 months of age. Median lag time from symptom onset to diagnosis varied between 3–12 months. The overall globe salvage rates ranged from 13% to 54.7%, with early intraocular disease having greater rates of vision preservation. A higher proportion of vision salvage (>50%) was found in recently concluded studies, mainly due to the use of intra-arterial chemotherapy after 2019. The pooled 5-year overall survival (OS) was 78.7%. Reported relapse rates ranged from 7% to 36%. Treatment abandonment rates varied between 10% to 58%.

Conclusion:

Our review shows globe salvage rates for RB in India match other low-middle-income countries, but 5-year OS is lower than in developed nations. The relapse rates are similar to the global rates. Proposed measures to optimize RB outcomes include parental counseling for early recognition, efforts to limit treatment abandonment, and improving access to specialized treatment.

Retinoblastoma (RB) is the commonest intraocular malignancy in the pediatric age group. The worldwide incidence is estimated to be about 11 cases per million in children under five years of age. The estimated incidence of retinoblastoma in India is ~2000 cases per year.[1] The reported 3-year survival rate in high-income countries is 99.5% as compared to 80.3% in children of low-middle income countries (LMICs).[2] The advanced stage at presentation, possibly attributable to limited awareness of symptoms, lack of universal access to optimal medical care, treatment refusal, and abandonment, contributes to poor outcomes in LMICs.[2,3] Delayed recognition leads to a higher proportion of patients with advanced disease and inferior outcomes. RB has been identified as an index cancer as per the World Health Organization (WHO) CURE-ALL initiative, and concerted efforts are underway to optimize the outcomes in our country.[4] It is, therefore, imperative to take stock of the outcomes published till date to establish a roadmap for the ongoing efforts. Several authors from India have published outcomes of retinoblastoma from their centers. We attempted a systematic survey of these studies, to investigate the trends and patterns of survival outcomes of this childhood malignancy in India.

Methods

The procedure of the current study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.[5] The PubMed and Google Scholar electronic database was searched from inception until April 2024 for English language studies. The reference list of the selected articles was also searched manually for finding additional studies matching the search criteria. The following terms were combined to maximize the search strategy: Retinoblastoma, India, pediatric, children, childhood, intra-arterial chemotherapy, outcome, survival, prognosis.

Selection criteria

The search strategy is depicted in Fig. 1.

Figure 1.

PRISMA flow diagram showing the search strategy for the purpose of this systematic review

Data collection

Data was extracted from each eligible article into a customized database. Extracted data included title, names of authors, location of the center, year of publication, number of patients, number of eyes treated, age group of patients, gender distribution, laterality of disease, group and stage at presentation, family history, presenting symptoms, lag period before diagnosis, type of chemotherapy used, rates of primary and secondary enucleation, overall survival (OS), event-free survival (EFS), progression-free survival (PFS), local control rates, globe salvage rates, mortality rates, rates of relapse/metastasis, and rates of treatment abandonment/non-compliance to treatment. When met with more than one study on the same cohort, the study with the most comprehensive data or with the longest follow-up was included.

Statistical analysis

A meta-analytic approach was employed to estimate pooled OS along with 95% confidence intervals (CIs) across the included studies. Due to anticipated clinical and methodological heterogeneity, a random-effects model was used for all pooled estimates. Forest plots were constructed to visually represent the effect sizes and their respective CIs. All statistical analyses were performed using a code-based computational approach, modeled on established meta-analytic principles. The analysis was carried out using custom scripts written in Python (version 3.11). The code used for analysis was manually verified to ensure accuracy and adherence to standard statistical methodology. Although traditional meta-analysis software like STATA or RevMan was not used, all results were cross-checked against published meta-analytic guidelines to maintain scientific rigor and reliability.

Results

Our search retrieved 255 results. We screened the titles and abstracts of all the articles and excluded 228 studies. Twenty-seven studies were assessed by full-text. We shortlisted 15 articles for which the survival outcomes or globe salvage rates were mentioned. The articles covered outcomes of retinoblastoma from 1990 to April 2024 in India. Two studies out of 15 were prospective, and 13 were retrospective in nature.

Demographic variables

Six articles included patients from the Northern zone, five articles from the Southern zone, two articles from the Central zone, one article from the Western zone, and one article from the Eastern zone of the country. Two studies were prospective.[6,7] The total number of patients was 4147, aged 5 days to 370 months. The mean/median age at presentation was included in 13 studies and varied. Gender distribution was mentioned in 13 out of 15 studies and included 2223 males (57%) and 1654 females (43%), giving an overall M: F ratio of 1.32:1, akin to data published from developed countries. Nearly two-thirds of patients presented with unilateral RB compared to bilateral disease (63% vs 37%). About 4% of patients had a family history of retinoblastoma. In our review, leukocoria was the most common presenting symptom (~70%) followed by redness/watering in eyes, proptosis, strabismus, and defective vision. In one article, 2.8% of cases were incidentally detected on routine examination.[8] The lag period between first symptom and presentation to a healthcare facility ranged from 0 to 120 months [Table 1]. Most studies reported a median lag time of 3 months.[9,10,11] Table 1 illustrates the demography and clinical features of RB reported in Indian studies till date.

Table 1.

Demography and clinical features of RB mentioned in various Indian studies

Authors	Location of center	Mean/median age in months	Gender distribution	Laterality of disease	History of RB in family	Presenting symptoms	Lag period before presentation
Reddy et al., 2007[12]	Hyderabad	–	M=277, F=183	U/L=272 B/L=188	4%	Lc (71%), ↓ VA (12%), propt (7%), strab (6%), pain (2%), redE (2%), shrunken eyes (1%)	–
Bakhshi et al., 2010[13]	Delhi	36 mo	M=16, F=9	U/L=17, B/L=8	–	Lc in 72% pts.	12 mo
V Radhakrishnan et al., 2012[6]	Delhi	36 mo	M=17, F=11	U/L=27, B/L=1	0%	–	6 mo
Ansari et al., 2012[14]	Delhi	U/L=32 mo B/L=26 mo	M=105, F=75	–	4.4%	Lc (74%), propt (11.5%), strab (8%), ↓ VA (6.5%).	–
Manjandavida Fairooz et al., 2014[15]	Hyderabad	25.2 mo	Total cases 101	Only U/L cases included	–		–
Shah et al., 2015[8]	Coimbatore	20.8 mo	M=62, F=43	U/L=68, B/L=38	3.8%	Lc, (76.5%), redE (8.5%), strab (6.6%), propt (2.8%), ↓ VA (2.8%), RE (2.8%)	–
Chawla et al., 2015[9]	Delhi	29 mo	M=367, F=233	U/L=406, B/L=194	6.3%	Lc (83%), propt (17%), redE (8.3%), strab (5.5%), (1%)	3 mo
Pant et al., 2017[16]	Lucknow	–	M=29, F=12	U/L=33, B/L=8	–	–	8 mo
Singh et al., 2017[10]	Chandigarh	30 mo	M=288, F=179	U/L=316 B/L=151	–	Lc (60.6%), strab (16.9%), hyperemia (8.1%), NV (7.8%), propt (4.4%), glu (0.5%)	3 mo
Gupta et al., 2018[11]	Lucknow	33 mo	M=118, F=82	U/L=152, B/L=48	4%	–	3 mo
Kaliki et al., 2019[17]	Hyderabad	29 mo	M=812, F=645	U/L=834 B/L=623	4% –	Lc (75%), propt 91 (6%), strab 77 (5%), redE 68 (5%)	–
Rishi et al., 2020[18]	Chennai	30.4 mo	M=10, F=5	U/L=6 B/L=9	0.5%	–	–
Hazarika et al., 2022[19]	Guwahati	14 mo	M=103, F=86	U/L=138, B/L=51			49 days
Khanna et al., 2023[20]	Mumbai	24 mo	Total cases 98	–			–
Kumar et al., 2023[7]	Delhi	13 mo	M=19 F=23	U/L=40 B/L=2	2.3%	Lc (100%), strab (23.8%), propt (2%), redE (2%), pain (2%)	–

M=Male, F=Female, U/L=Unilateral, B/L=Bilateral, mo=months, Leucocoria=Lc, Strabismus=Strab, decreased visual acquity=↓VA, Red eye=RedE, proptosis=propt, glaucoma=glu, neovascularization=NV, routine examination=RE

Treatment strategies employed

All of the selected articles used the International Classification for Intraocular Retinoblastoma (ICRB) for grouping intraocular disease and the International Retinoblastoma Staging System (IRSS) for staging extraocular disease, except two studies, which used the Reese-Ellsworth classification.[14,15] CEMRI of the orbit was used for definitive diagnosis, and MRI brain, CSF examination, and bone marrow examination were used for staging the tumor. Local therapies like transpupillary thermotherapy/cryotherapy/subtenon carboplatin/intravitreal chemotherapy/external beam radiotherapy (EBRT) were used for globe salvage.[6,7,8,9,10,11,12,13,14,15,16,17,18,19,20] The majority of patients were treated with neoadjuvant chemotherapy, enucleation/exenteration, followed by adjuvant chemotherapy +/− external beam radiotherapy (EBRT) (~40 Gy). Almost all Indian centers have used vincristine, carboplatin, and etoposide (VEC) uniformly as agents for intravenous chemotherapy.[8,9,10,11,12,13,14,15,16,18] One study used vincristine, cisplatin, etoposide, cyclophosphamide (OPEC) prior to 2007 and VEC after.[10] Rates of primary enucleation ranged from 30% to 78.5%, and those of secondary enucleation ranged from 20% to 35.6%. Intra-arterial chemotherapy (IAC) was used as a treatment modality in three studies published in 2020–2023.[7,18,20] Melphalan, topotecan, and carboplatin were used as agents for IAC.[7,18,20] Table 2 demonstrates the treatment modalities employed by different centers in India for the management of RB.

Table 2.

Treatment modalities employed in various studies

Authors	Type of RB			Only LT	Prim/sec enu	LT+/- CRD	EBRT + other therapies	CT +/- other therapies	CRD + enu
Reddy et al., 2007[12]	In+Ex In – 94% Ex – 6%			11%	Prim enu – 52%	26%	12%	4%	–
Bakhshi et al., 2010[13]	Ex IRSS2 – 24% IRSS3 – 76%			–	Prim enu – 76% Sec enu-20%	–	92%	–	20%
Radhakrishnan et al., 2012[6]	Ex All IRSS3			–	Prim enu – 78.5%	–	–	–	–
Ansari et al., 2012[14]	In Grp1,2 – 13% Grp 3 – 6% Grp 4,5 – 67% Missing info – 14%			–	–	–	35%	–	80%
Manjandavida Fairooz et al., 2014[15]	In Grp C – 20% Grp D – 40% Grp E – 40%			–	–	100% (Subtenon carboplatin in 72% with diffuse vitreous seeds, i.e., Grp D and E disease)	32.6%	–	–
Shah et al., 2015[8]	In+Ex Grp A – 10% Grp B – 15% Grp C – 2% Grp D – 32% IRSS 2 and worse – 41%			10% (Only grp A)	Prim enu – 60.4% (U/L Grp D and E)	42% (Subtenon carboplatin in 26% with Grp C and D disease)	8%		60.4%
Chawla et al., 2015[9]	In+Ex In – 73% IRSS 3 – 23% IRSS 4 – 4%			–	Prim enu – 49.4% in In cases. All Grp E eyes (64%) underwent prim enu Sec enu – 22.4% in In cases	36.6% rec’d TTT/cryotherapy. 34.7% rec’d CRD among In tumors	5.3% among In cases	–	–
Pant et al., 2017[16]	Ex IRSS 3 – 63% IRSS 4 – 37%			–	–	–	31% of IRSS3 pts	–	57.7% of IRSS3 pts
Singh et al., 2017[10]	In+Ex Grp A – 2% Grp B – 10% Grp C – 2% Grp D – 6% Grp E – 44% Ex – 36%			–	Prim enu – 33.7% Sec enu – 35.6%	8% (LT included laser/cryotherapy)	17.8%	65.7%
Gupta et al., 2018[11]	In+Ex Grp A – 4% Grp B – 6% Grp C – 4% Grp D – 36% Grp E and worse – 50%			–	None	13.7% (All Grp A+Grp B eyes)	51.5%	100%	83.46% (All Grp D + Grp E underwent enu)
Kaliki et al., 2019[17]	In+Ex (In=91%, Ex – 9%)			–	Prim enu – 35%	3% rec’d cryotherapy 3% rec’d TTT	–	60%	–
	Grp A-6% Grp B – 15% Grp C – 7% Grp D – 22% Grp E – 50%	IRSS 0 – 45% IRSS 1 – 45% IRSS 2 – 1.5% IRSS 3 – 6% IRSS 4 – 2.5%
Rishi et al., 2020[18]	In Grp B – 6% Grp C – 20% Grp D – 60% Grp E – 14%			–	–	–	–	60% pts rec’d IAC + LT, including cryotherapy/TTT/EBRT/intravitreal CT 33% rec’d only IAC which included 55% Grp D and 33% Grp C eyes	40% (All pts rec’d IAC as well)
Hazarika et al., 2022[19]	In+Ex In – 71% Ex – 29%			–	–	33% (LT included cryotherapy)	39%	64%	–
Khanna et al., 2023[20]	In+Ex			–	Prim enu – 53% Sec enu – 27%	–	24%	52% rec’d systemic CT. 11% rec’d IAC.	–
	Grp B – 4% Grp C – 2% Grp D – 22% Grp E – 73%		IRSS 0 – 14% IRSS 1 – 53% IRSS 2 – 10% IRSS 3 – 22% IRSS 4 – 1%
Kumar et al., 2023[7]	In Grp D – 5% Grp E – 95%			–	Prim enu – 29% in Grp E Sec enu – 20% in Grp E	–	–	64% rec’d IAC. FT after IAC included TTT and cryotherapy	–

IAC=Intra-arterial chemotherapy, enu=enucleation, In=Intraocular, Ex=Extraocular, TTT=Transpupillary thermotherapy, CRD=Chemoreduction, FT=Focal therapy, LT=Local therapy, Group=Grp, prim=primary, sec=secondary, CT=chemotherapy, received=rec’d, patients=pts

Outcomes

The overall globe salvage rate ranged from 13% to 54.7% in various study cohorts, which primarily included patients with advanced intraocular RB.[7,12,19,20] Globe salvage rate for Groups A and B was 100%.[8,9,10,11] The globe salvage rate for patients with Group C disease varied from 67% to 100% and that of Group D disease from 0% to 100%.[7,8,9,10,11,15,18] Five articles reported globe salvage rates for Group E disease. Out of them, two studies reported a global salvage rate of 0%, and the other three reported salvage rates ≥ 50% for Group E disease.[7,10,11,15,18]

The overall globe survival rate in one study for patients treated with IAC was 93% at 12 months, 76% at 24 months, and 66% at 26 and 48 months.[18]

Three studies evaluated the outcome of extraocular retinoblastoma exclusively.[6,13,16] The OS rates in these studies were 87.5% at 1 year, 40.4% to 55.6% at 2 years, and 39.7% to 48% at 3 years.

Eight studies have evaluated the outcome of both intra and extraocular retinoblastoma.[8,9,10,11,12,17,19,20] The OS rates at 1 year follow-up ranged from 74% to 94%, that at 2 years were 65.5% and 94%, and that at 3 years ranged from 63.3% to 91%. The OS rates at 5 years follow-up ranged from 62.2% to 90%. The OS at 10 years follow-up was 89%, reported in one study.[16]

A total of three studies reported 5-year OS, which was used in meta-analysis. The pooled 5-year OS was estimated to be 78.7% (95% CI: 62.4%–89.2%), using random-effects model, due to substantial between-study heterogeneity. A forest plot summarizing the individual and pooled estimates is presented in Fig. 2.

Figure 2.

Forest plot showing the survival outcome of the RB patients reported in various studies

Univariate meta-regression using weighted least squares was performed to explore potential sources of heterogeneity. The year of publication showed non-significant association with survival (coefficient = 0.1935, P = 0.261; R² = 0.39), although a positive trend was observed. The sample size also demonstrated a positive trend with survival, approaching statistical significance (coefficient = 0.0012, P = 0.091; R² = 0.67).

The EFS rates in extraocular retinoblastoma were 54% at 18 months and 33.3% at 26.3 months follow-up.[6,13] The local control (LC) rates were 55% at 28 months, 32.2% at 60 months, and 97.6% at 60 months.[10,14,20]

Data on relapse/metastasis were included in seven studies and ranged from 0% to 36% at last follow-up. The majority of patients had CNS metastasis, followed by skeletal/nodal metastasis. One study reported the development of secondary acute myeloid leukemia, and another reported the development of a secondary intracranial tumor (fibroblastic meningioma of the sphenoid bone).[10,16] Two studies reported no distant metastasis at a follow-up of 48 months and 30.2 months.[8,15]

The mortality rate ranged from 0 to 37% in different cohorts. Most of these patients died due to relapse or metastases, due to an advanced disease stage. Few died due to treatment complications.[7,8,9,10,11,16,17,20] The overall pooled mortality rate was 12.3% (95% CI: 11.2%–13.5%).

The proportion of patients who were either non-complaint or refused/abandoned treatment ranged from 10% to 58% in various studies.[6,9,10,11,16,19] The calculated pooled treatment abandonment rate was 22.6% (95% CI: 20.6%–24.8%).

Table 3 summarizes the survival outcomes of RB in India till date.

Table 3.

Survival outcomes, globe salvage rates, mortality and relapse rates, and rates of treatment abandonment in Indian studies published till date

Authors	Overall globe salvage/survival rates	Globe salvage rates for individual groups	OS	EFS	LC	Rates of metastasis/relapse/progression	MR at last follow-up	Rates of abandonment/non-compliance to treatment
Reddy et al., 2007[12]	24%	–	94% at 24 mo	–	–	–	–	–
Bakhshi et al., 2010[13]	–	–	48% at 34 mo	54% at 18 mo	–	52%	–	–
V Radhakrishnan et al., 2012[6]	–	–	40.4% at 26.3 mo	33.3% at 26.3 mo	–	–	–	32%
Ansari et al., 2012[14]	–	–	–	–	55% at 28 mo	7%	–	–
Manjandavida Fairooz et al., 2014[15]	–	Grp C – 95% Grp D – 85% Grp E – 57.5%	–	–	–	None	None	–
Shah et al., 2015[8]	-	Grp A – 100% Grp B – 100% Grp C – 100% Grp D – 29.5%	89.6% at 36 mo	–	–	10	10.4%	–
Chawla et al., 2015[9]	-	GrpA – 100% Grp B – 94% Grp C – 83% Grp D – 54%	83% at 12 mo 73% at 24 mo 68% at 36 mo 65% at 60 mo	–	–	9%	24%	10%
Pant et al., 2017[16]	–	–	87.5% at 12 mo 55.6% at 24 mo 39.7% at 36 mo, for IRSS3 pts	–	–	17%	22%	41%
Singh et al., 2017[10]	–	Grp A – 100% Grp B – 100% Grp C – 94.7% Grp D – 17.1% Grp E – 0% at 28.5 mo	–	–	32.2% at 60 mo	7%	3.8%	43.5%
Gupta et al., 2018[11]	–	Grp A – 100% Grp B – 100% Grp C – 88.9% Grp D- 0% Grp E- 0%	74% at 12 mo 65.5% at 24 mo 63.3% at 36 mo 62.2% at 60 mo	–	–	–	37%	14%
Kaliki et al., 2019[17]	–	–	94% at 12 mo 91% at 36 mo 90% at 60 mo 89% at 120 mo	–	–	–	8%	–
Rishi et al., 2020[18]	Globe survival rates – 93% at 12 mo 76% at 24 mo 66% at 36 and 48 mo	Grp B – 100% Grp C – 67% Grp D – 67% Grp E – 50%	–	–	–	–	–	–
Hazarika et al., 2022[19]	13%	–	76% at 60 mo	–	–	–	–	15%
Khanna et al., 2023[20]	16%	–	89.5% at 60 mo	88% at 60 mo	97.6% at 60 mo	12%	10%	–
Kumar et al., 2023[7]	54.7% at 12 mo	Grp D – 100% Grp E – 52.5% at 12 mo	–	–	–	–	2.3%	–

OS – Overall survival, EFS – Event-free survival, LC – Local control, MR – Mortality rate, mo=months, Group=Grp, patients=pts

Discussion

The present review shows a median age at diagnosis between 24 and 36 months of age. This observation is consistent with other studies, which have found a significantly higher median age at diagnosis in children from LMICs as compared to high-income countries (HICs) (24.4 months vs 14 months, P < 0.001).[21,22] This has largely been attributed to delayed recognition of symptoms. Encouragingly, the more recent studies in our review show a younger age at presentation.[19,7]

The sex ratio of RB in our study is 1.32. A multicentric study has reported a sex ratio of 1.22 in LMICs and 1.25 in HICs.[23] Another study has reported a sex ratio of 1.4 in South Asia.[22] These findings indicate that there is no significant gender bias against the girl child.

Our review found 2/3^rd of cases to be unilateral and 1/3^rd bilateral and a positive family history in 4% of the patients, which is consistent with other studies.[22] Globally, leukocoria followed by strabismus and proptosis are the commonest symptoms at presentation.[21] In our study, the median lag time from first symptom to diagnosis varied between 3–12 months. Longer distance to the nearest healthcare facility, presentation to a physician who is not aware of the disease, or presentation to a primary healthcare center where there is a lack of facilities for definitive diagnosis may be responsible for such lag time.[24]

The treatment strategies employed for management have gradually evolved over the decades. Genetic testing, neonatal screening, and periodic ophthalmic examination have helped in early detection of disease and hence early institution of definitive therapies. Enucleation and EBRT were the primary modalities of therapy in the early 1990s. Systemic intravenous chemotherapy and focal therapies emerged in the late 1990s, leading to higher rates of globe salvage and vision preservation.[25] However, enucleation rates are still notably higher in LMICs (67.1%) compared to HICs (59.7%). The rates of primary enucleation in our review ranged from 30% to 78.5%. The advanced stage at presentation in developing countries often makes it difficult to salvage the globe, leading to increased proportion of primary enucleation.[2,21]

IAC would be the ideal modality for localized disease, but the uptake in India for this modality is low, with limited access to expertise and high cost. In our review, we found three studies published between 2020–2023 that used IAC. One study used single-agent melphalan, another used melphalan and topotecan, and the other used a triple drug regimen (melphalan, carboplatin, topotecan), which dramatically increased the globe salvage rates for Group E disease.[7,18,20] Over the years, there was a trend toward an increasing proportion of patients receiving systemic chemotherapy/IAC and decreasing rates of primary enucleation.[17] For controlling vitreous seeds, intravitreal chemotherapy has been found to be useful. When used in conjunction with IAC, this combined modality of treatment can dramatically improve the globe salvage rates and decrease the rates of EBRT, thereby reducing the side effects of EBRT.[7,25]

The overall globe salvage rates found in our review ranged from 13% to 54.7% in different cohorts, with early intraocular disease having higher rates of vision preservation compared to advanced intraocular or extraocular RB [Table 3]. This finding is at par with other studies from LMICs, which show a global salvage rate of 28% (9 to 51%) in the last decade for advanced intraocular disease.[26] However, we observed a higher proportion of vision salvage (>50%) in recently concluded studies mainly due to the increasing use of IAC.[7,18]

The OS at 5 years ranged from 65% to 90% (pooled OS 78.7%). Although not statistically significant, recent studies demonstrated a trend toward improved OS compared to earlier ones. The near-significant association between sample size and survival could imply that larger, potentially better-resourced studies tend to report more favorable outcomes. However, the observed OS in our review is still lower than the published OS in HICs.[26] The marked disparity between the globe salvage rates and survival outcomes of RB in our country compared to the Western world is due to late presentation to a healthcare facility, leading to delayed diagnosis of the disease. In our review, the presence of tumor at the cut end of the optic nerve, higher rates of subretinal and vitreous seeds, and scleral/choroidal/ciliary body involvement were the major factors leading to worse OS and EFS.[6,7,10,12,15]

The reported rates of relapse of RB ranged from 7% to 36% in our review, which is similar to the global retinoblastoma relapse rate (6% to 45%).[27] We found two cases of second neoplasm, which again highlights the adverse effects of EBRT and the need for reducing the usage of the same. After treatment, follow-up is of paramount importance for early diagnosis of relapse and also to diagnose the late effects in RB survivor, including retardation of growth, diminished vision and hearing, intellectual disability, and orbital hypoplasia.[28]

The pooled mortality rate found in our review was 12.3%, which is better compared to the mortality rate in LMICs (15.4%) but much worse than that in HICs (0.8%).[2]

Abandonment is a major cause of treatment failure in our setting, with reported rates ranging from 10% to 58% (pooled treatment abandonment rate 22.6%). Common reasons for treatment abandonment include logistical and financial constraints and refusal to enucleate.[29]

Conclusion

In order to improve the gap in survival outcomes of RB between the developing and developed nations, dedicated efforts are the need of the hour. With RB being declared as an index cancer by WHO, attention will be drawn toward this childhood malignancy and hopefully increase the globe salvage rates through modern technology and proper allocation of healthcare budget.

Proposed measures for optimizing the outcomes of RB in our country include enhancing awareness regarding early recognition by parental/community education, promoting the acceptance of enucleation by involving survivors, efforts to limit abandonment of treatment, and improving access to specialized treatment.

Limitations

The limitation of this study is that the data accrued for this systematic survey is largely retrospective and from single centers and might not be reflective of the regional variations in the clinical presentation and treatment outcomes.

Conflicts of interest:

There are no conflicts of interest.

Funding Statement

Nil.