The Cure Gap, Measured Yearly: The Mortality-to-Incidence Ratio as a Registry-Free Tracer of Childhood Cancer Care, 1990–2023

Background: Survival after childhood cancer is strikingly unequal across the development spectrum, yet population-based cancer registries, the gold standard for survival measurement, are absent or incomplete in most low- and middle-income countries (LMICs), precisely where the burden is concentrated. The World Health Organization (WHO) Global Initiative for Childhood Cancer (GICC) targets at least 60% survival by 2030, but no registry-free, annually updatable, internationally comparable tracer of childhood cancer care-system performance is currently in routine use. We evaluated the mortality-to-incidence ratio (M/I), computed from Global Burden of Disease (GBD) estimates, as such a tracer.Methods: We extracted deaths and incident cases (ages 0–19 years, both sexes, 1990–2023) for leukemia, retinoblastoma, and a 14-cause aggregate aligned with the International Classification of Childhood Cancer from GBD 2023. M/I was computed as deaths divided by incidence, with Monte Carlo propagation of uncertainty intervals (UIs). A cure gap index was defined as the ratio of low-SDI to high-SDI M/I. External validity was assessed by reconciliation against registry-based survival anchors (CONCORD-3; China's National Childhood Cancer Surveillance annual report) and against the expected direction of the socio-demographic index (SDI) gradient, under an explicit construct-difference framework. Sensitivity to incidence under-ascertainment was quantified with scenario corrections (u = 0–43%).Results: Global leukemia M/I declined monotonically from 62.7% in 1990 to 46.6% (95% UI 37.1–60.1) in 2023 (estimated annual percentage change [EAPC] −0.975% per year). In 2023, M/I fell monotonically across SDI quintiles for all three calibers (leukemia 66.99% in low-SDI vs 24.35% in high-SDI countries; retinoblastoma 93.57% vs 7.23%; 14-cause aggregate 55.67% vs 19.15%), and across 21 GBD regions leukemia M/I ranged 6.5-fold, from 72.5% (Oceania) to 11.2% (Western Europe). The cure gap index widened from 1.38× to 2.75× for leukemia (average +2.47% per year, decelerating to about +1.3% per year over the most recent decade) and from 3.07× to 12.95× for retinoblastoma. Criterion reconciliation was direction-consistent throughout: the GBD-modeled retinoblastoma M/I for China (8.6%) lay within 1.0 percentage point (pp) of the registry-implied case fatality (9.6%), and regional implied survival (1 − M/I) tracked the CONCORD-3 anchors across their full range (49.8–95.2%), including a near-exact agreement for Andean Latin America (49.77% vs Ecuador 49.8%, a 0.03 pp difference) that we treat as partly endogenous corroboration rather than independent validation. Under a 43% global-average under-ascertainment scenario the inequality persisted (corrected gap indices 1.57×–7.38×), and it persisted even at the western African regional rate of 57% (leukemia gap index 1.18×).Conclusion: The M/I is a smooth, annually updatable, registry-free tracer whose levels, gradients, and trends corroborate independent survival evidence. It cannot replace registry-based survival, but it can monitor the cure gap, and its widening, in the many settings where registries do not yet exist.

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Preprints.org
Published
2026-10-28
DOI
https://doi.org/10.20944/preprints202610.2841.v1
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Global Cancer Incidence and Screening
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preprint

The Cure Gap, Measured Yearly: The Mortality-to-Incidence Ratio as a Registry-Free Tracer of Childhood Cancer Care, 1990–2023

Deze Li, Chen Shen, Xiaotong Wang, Hao Chen
Preprints.org
Global Cancer Incidence and Screening
preprint

The Cure Gap, Measured Yearly: The Mortality-to-Incidence Ratio as a Registry-Free Tracer of Childhood Cancer Care, 1990–2023

Deze Li, Chen Shen, Xiaotong Wang, Hao Chen
preprint en

Abstract

Background: Survival after childhood cancer is strikingly unequal across the development spectrum, yet population-based cancer registries, the gold standard for survival measurement, are absent or incomplete in most low- and middle-income countries (LMICs), precisely where the burden is concentrated. The World Health Organization (WHO) Global Initiative for Childhood Cancer (GICC) targets at least 60% survival by 2030, but no registry-free, annually updatable, internationally comparable tracer of childhood cancer care-system performance is currently in routine use. We evaluated the mortality-to-incidence ratio (M/I), computed from Global Burden of Disease (GBD) estimates, as such a tracer.Methods: We extracted deaths and incident cases (ages 0–19 years, both sexes, 1990–2023) for leukemia, retinoblastoma, and a 14-cause aggregate aligned with the International Classification of Childhood Cancer from GBD 2023. M/I was computed as deaths divided by incidence, with Monte Carlo propagation of uncertainty intervals (UIs). A cure gap index was defined as the ratio of low-SDI to high-SDI M/I. External validity was assessed by reconciliation against registry-based survival anchors (CONCORD-3; China's National Childhood Cancer Surveillance annual report) and against the expected direction of the socio-demographic index (SDI) gradient, under an explicit construct-difference framework. Sensitivity to incidence under-ascertainment was quantified with scenario corrections (u = 0–43%).Results: Global leukemia M/I declined monotonically from 62.7% in 1990 to 46.6% (95% UI 37.1–60.1) in 2023 (estimated annual percentage change [EAPC] −0.975% per year). In 2023, M/I fell monotonically across SDI quintiles for all three calibers (leukemia 66.99% in low-SDI vs 24.35% in high-SDI countries; retinoblastoma 93.57% vs 7.23%; 14-cause aggregate 55.67% vs 19.15%), and across 21 GBD regions leukemia M/I ranged 6.5-fold, from 72.5% (Oceania) to 11.2% (Western Europe). The cure gap index widened from 1.38× to 2.75× for leukemia (average +2.47% per year, decelerating to about +1.3% per year over the most recent decade) and from 3.07× to 12.95× for retinoblastoma. Criterion reconciliation was direction-consistent throughout: the GBD-modeled retinoblastoma M/I for China (8.6%) lay within 1.0 percentage point (pp) of the registry-implied case fatality (9.6%), and regional implied survival (1 − M/I) tracked the CONCORD-3 anchors across their full range (49.8–95.2%), including a near-exact agreement for Andean Latin America (49.77% vs Ecuador 49.8%, a 0.03 pp difference) that we treat as partly endogenous corroboration rather than independent validation. Under a 43% global-average under-ascertainment scenario the inequality persisted (corrected gap indices 1.57×–7.38×), and it persisted even at the western African regional rate of 57% (leukemia gap index 1.18×).Conclusion: The M/I is a smooth, annually updatable, registry-free tracer whose levels, gradients, and trends corroborate independent survival evidence. It cannot replace registry-based survival, but it can monitor the cure gap, and its widening, in the many settings where registries do not yet exist.

Preprints.org
Global Cancer Incidence and Screening
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