Global retinoblastoma survival and globe preservation: a systematic review and meta-analysis of associations with socioeconomic and health-care factors.

Background: Despite advancements in globe-preserving treatments, improvements in retinoblastoma outcomes are inconsistent across income levels and geographical locations. We aimed to investigate trends in global retinoblastoma survival and globe preservation during the past 40 years. We also examined associated socioeconomic and health-care factors and global survival disparity.

Methods: We did a systematic review and meta-analysis by screening articles in any language in nine databases (PubMed, Embase, ScienceDirect, Web of Science, OpenGrey, Global Burden of Disease, Global Health Data Exchange, Global Index Medicus, and International Agency for the Prevention of Blindness) published between Jan 1, 1981, and Oct 8, 2021. We screened for articles that described retinoblastoma overall survival or globe salvage, or both. All reported studies were subsequently stratified into four periods: 1980-89, 1990-99, 2000-09, and 2010-20. Indicators on socioeconomic and health-care factors were extracted from the World Bank and WHO. Ophthalmology-related indicators were further parsed from the International Agency for the Prevention of Blindness. Between-study heterogeneities by income level were assessed by mixed-effect meta-analysis. Associations of retinoblastoma outcome with socioeconomic and health-care factors and factors for survival prediction were investigated by multivariable linear regressions. This study is registered with PROSPERO, number CRD42020221556.

Findings: Our search identified 14 621 articles, of which 314 studies were included for analysis after screening, including 38 130 patients from 80 regions globally presenting during 1980-2020. 255 articles were entered for time-trend meta-analysis, covering 29 106 patients from 73 countries. Both overall survival (from 79% [95% CI 74-84] to 88% [83-93]; p=0·017) and globe salvage rate (from 22% [14-32] to 44% [36-52]; p=0·0003) improved significantly over the four decades. Wide disparities were observed between higher-income and lower-income countries. Overall survival, globe salvage, and globe salvage for advanced intraocular disease correlated positively with income level. Higher overall survival was associated with lower Gini index (p=0·0001) and with populations that had smaller percentages living in rural areas (p=0·0005). Higher globe salvage was associated with better health-care financing and accessibility (p=0·030). Overall survival (p=0·0024) and globe salvage (p=0·022) were both associated positively with education level. Survival gaps were observed in sub-Saharan Africa and southeast and southwest Asia.

Interpretation: Retinoblastoma treatment outcomes have improved globally over the past four decades but large disparities persist between higher-income and lower-income countries, with some areas having major survival gaps. Targeted health-care policy making with increased health-care financing and accessibility are needed in low-income and lower-middle-income countries to improve retinoblastoma outcomes worldwide.

Funding: Health and Medical Research Fund (Hong Kong) and Children Cancer's Foundation (Hong Kong).