Charles A. Stiller- National Cancer Registration and Analysis Service, National Disease Registration Service, NHS England, London, United Kingdom
Introduction: The development of effective treatment for many childhood cancers has led to dramatic increases in survival rates at the population level, at least in affluent industrialized countries. Studies of survival in numerous populations have been published, but population-based survival estimates that are essential for monitoring and planning are still lacking in many countries. There is no comprehensive account of the type and extent of available information on this topic. A scoping review of population-based studies of childhood cancer in the 21st century was carried out with the aim of repairing this omission.
Methods: The electronic databases PubMed and Web of Science were searched, supplemented by the author's bibliographic files.
Results: The searches produced 5,490 references, of which 303 reported population-based studies containing at least one estimate of 5-year survival for children with cancer diagnosed during a period whose central year was 2001 or later. Overall, 75% of high-income countries with a child population ≥50,000 were represented in these studies, compared with 47% of upper middle income countries, 16% of lower middle income countries and 8% of low income countries. Among countries that were represented in population-based studies, 29% of high income countries were only represented in studies involving multiple countries compared with 75% of those in lower income categories. Similar contrasts were found between countries with very high Human Development Index and those in lower categories of Human Development Index.
Discussion: Wider availability of robust information on survival at population level will be essential for monitoring progress toward the goal set by the World Health Organization's Global Initiative for Childhood Cancer of 60% survival globally for children and adolescents with cancer by the year 2030. Increasing the coverage and quality of cancer registration and death notification in as many lower-resource countries as possible would in turn increase the volume and geographic spread of the data from which survival rates can be estimated for those countries. International collaborations whose results are underpinned by uniform procedures for data validation and analysis will continue to play a vital part in enabling comparison of childhood cancer survival between populations.
1 Introduction
The development of effective treatments for many childhood cancers over the past 60 years is one of the great success stories of oncology (1, 2). In consequence, there have been dramatic increases in survival rates for childhood cancer at the population level, at least in affluent industrialized countries (3, 4). Some of these increases have been shown to occur concurrently with the adoption of successive trial protocols for particular types of childhood cancer (5, 6).
Impressive results have also been reported from specialist centers in many less well-resourced settings. However, population-based estimates of survival of all patients, including those not treated at specialist centers, are essential for monitoring and planning but are still lacking in many countries. This absence prompted Ward et al. (7) to carry out a simulation study to estimate survival for virtually every country in the world including those for which hard data were missing. In the same year, Girardi et al. (8) published a systematic review of worldwide trends in survival from two principal types of childhood brain tumor. Since then, studies of survival from childhood cancer in numerous populations have continued to be published, but there has apparently been no comprehensive delineation of the type and extent of the available information on this topic. The present scoping review was carried out in order to repair this omission.
2 Materials and methods
Eligible publications were defined as those that provided at least one population-based estimate of survival for children diagnosed with cancer according to the following criteria.
Data had to refer to cases arising in a defined population, usually compiled by a population-based cancer registry (PBCR) and were not restricted to patients receiving any particular treatment modality or modalities.
Following Girardi et al. (8), survival estimates had to be at 5 years after diagnosis. Eligibilty was broadened, however, to include endpoints other than death from any cause, thus papers reporting relative survival, net survival, event-free survival, cancer-specific survival or disease-specific survival could also be included.
Age range at diagnosis: lower bound ≤ 14 years and upper bound <20years.
Calendar period of diagnosis: wholly contained within a period whose central year was 2001 or later (including periods of an even number of years in length whose central years were 2000 and 2001).
Two online databases, PubMed and Web of Science, were searched for publications satisfying the above criteria. The search strategies are presented in the Appendix. The results of these searches were supplemented by review of additional publications from 2001 onwards in the author's bibliography files on descriptive epidemiology of childhood cancer. Eligible papers were restricted to those published in peer-reviewed journals. Conference abstracts were excluded. There were no language restrictions.
Throughout this review, the French West Indies have been treated as a single territory and Hong Kong and Macau have been included with China. For analyses by world region, Mexico, which is geographically in North America but more closely aligned socioeconomically and culturally with Latin America, was included in the category of America (Central and Caribbean); for similar reasons, Cyprus, which is geographically in western Asia, was included in the category of Europe.
3 Results
3.1 Literature searches
The searches of PubMed and Web of Science together yielded 5,490 references, with a further 383 from the author's bibliography files giving a grand total of 5,873 (Figure 1). After elimination of 1,010 duplicates and 574 articles published before 2001, 4,289 records remained for further assessment. On the basis of title and abstract, 3,190 references were excluded because they did not satisfy the eligibility criteria listed above. Full text was unavailable for 32 records. The remaining 1,067 were subjected to full-text review, leading to the exclusion of 764 because of failure to satisfy one or more of the eligibility criteria. There were thus a final total of 303 eligible publications, 29 of which were editions of two series of American annual reports.
Figure 1. PRISMA flow diagram for scoping review of global population-based childhood cancer survival.
3.2 United States annual series
The American Cancer Society “Cancer Statistics” reports for 2009 onwards have reported 5-year relative survival for childhood cancer diagnosed mainly or entirely in the 21st century, based on data from the Surveillance, Epidemiology and End Results (SEER) Program, thus the 16 reports issued in 2009–2024 were eligible for this review (9–24). The 2009–2016 editions (9–16) documented survival trends from 1975 onwards, with the most recent year of diagnosis being 5 years before the year of publication. Survival data in the editions for 2017 onwards (17–24) have covered a single 7-year period of diagnosis, the most recent year of diagnosis again being 5 years before the year of publication. Diagnoses have been classified according to the International Classification of Childhood Cancer, Third Edition (ICCC-3), in which the categories are defined by ICD-O-3 codes (25). Non-malignant central nervous system (CNS) tumors are excluded with the sole exception of pilocytic astrocytoma, which continued to be defined as malignant for the purposes of SEER when it was downgraded to uncertain behavior in ICD-O-3.
The annual statistical reports of the Central Brain Tumor Registry of the United States (CBTRUS) were initially self-published, but from 2012 they have been issued as supplements to Neuro Oncology. Each of these reports has presented 5-year relative survival for children under 15 years of age who were diagnosed during the 5-year period beginning 7 years before the year of publication, thus all 13 of the reports for 2012–2024 were eligible (26–38). Survival data were derived from the SEER-18 registries in the reports for 2012–2018 (26–32), and from NPCR registries in those for 2019 onwards (33–38). Diagnoses have been classified according to a scheme developed by CBTRUS and based on ICD-O-3 codes. Malignant and non-malignant tumors have been included throughout. Additional CBTRUS reports on childhood and adolescent patients that were published in 2022 and 2023 and are considered under “Other publications” below.
3.3 Other publications
Details of the remaining 274 eligible publications are shown in Table 1. Of these, 245 reported survival within a single country or territory, with 44 different countries represented. Data from the United States were analyzed in 93 (38%) of the 245 single-country studies. The great majority of these United States studies (75/93) were based exclusively on data from the SEER Program, though a substantial number of the analyses were conducted in other countries. Other countries represented by at least five single-country studies were the Netherlands (n = 17), Australia (n = 15), the United Kingdom (n = 11), France (Metropolitan) and Spain (n=8 each), Canada, South Korea and Germany (n = 7 each), Thailand (n = 6), Brazil and Sweden (n = 5 each).
Table 1. Studies included in the review. American Cancer Society “Cancer Statistics” annual series and CBTRUS annual statistical reports are excluded.
The other 29 publications were based on data from more than one country and were mostly products of established international collaborations. Eight papers from successive iterations of EUROCARE and its associated studies RARECARE and HAEMACARE have between them covered all types of childhood cancer in a large number of European countries (39–46). Five papers have presented international results from the CONCORD collaboration on population-based cancer survival worldwide (47–51) and a further paper reported detailed analyses of CONCORD data from 37 states in the United States (52). Leukemia was the only childhood cancer included in CONCORD-2 (50–52). CONCORD-3 expanded its coverage of childhood cancers to leukemia, lymphomas and CNS tumors (47–49). A collaboration between varying numbers of population-based cancer registries in Southern and Eastern Europe reported on survival from various childhood cancers in their respective countries in a series of seven papers, four of which also included United States data from the SEER Program (53–59). Finally, nine papers were from one-off studies that compared results between two, three, or four countries (60–68).
The 29 multinational papers included data not only from many countries that were represented by single-country studies, but also from a further 37 countries that did not have any eligible single-country publications in this review. Thus, a total of 80 countries and territories worldwide had their survival data included in at least one eligible paper, but for 37/80 (46%) this only occurred in the context of multinational studies. The proportion of countries that were only represented in multinational papers varied by continent, from zero in North America and Oceania to 12/35 (34%) in Europe, 5/11 (45%) in the Caribbean, Central and South America, 10/18 (56%) in Asia and 10/12 (83%) in Africa. Transferring Mexico and Cyprus to the groups of North American and Asian countries respectively would make little difference to this pattern.
3.4 Disease classifications and outcome measures
Definition and classification of diagnostic categories included in studies was nearly always by ICCC-3, by the CBTRUS classification of CNS tumors, or by ICD-O-3. Studies covering CNS tumors usually stated whether non-malignant CNS tumors were included in the analyses. Inclusion or exclusion of skin carcinomas or non-melanoma skin cancer was less frequently specified. A considerable variety of outcome measures were used. The most frequent were observed survival and relative or net survival, but some studies reported event-free, cancer-specific or disease-specific survival.
3.5 Characteristics of countries and territories represented in included publications
The only territory with an estimated child population below 50,000 to be represented among the eligible studies was the Faroe Islands (69). Table 2 shows, for all countries and territories with a child population of at least 50,000, their representation in studies covered by this review and in major international cancer survival studies, together with information on World Bank Income Group, Human Development Index, the presence of population-based cancer registration, and completeness of death registration.
Table 2. Countries and territories with child population of at least 50,000. Size of child population (315), World Bank per capita income category (316), Human Development Index (HDI) (317), presence of population-based cancer registration for age 0–14 during the study period (PBCR) (72, 318, 319), completeness of death registration (320), inclusion of published results in this review, and participation in CONCORD, EUROCARE, HAEMACARE, and RARECARE.
Countries were more likely to be represented in population-based studies of childhood cancer included in this review if they were in higher categories of World Bank income classification and Human Development Index (HDI; Table 3). Overall, 75% of high-income countries (HIC) were represented, compared with 47% of upper-middle-income countries (UMIC), 16% of lower-middle-income countries (LMIC) and 8% of low-income countries (LIC). Similarly, 79% of countries with Very High HDI were represented, compared with 45% of those with High HDI, 11% of those with Medium HDI and 9% of those with Low HDI. This pattern was repeated across all continents except the Caribbean, Central and South America, where there was a marked preponderance of very small countries among those in the highest categories of each of the two indices.
Table 3. Publication of survival results included in this review for countries in each continent with child population of at least 50,000 by World Bank per capita income category and Human Development Index (HDI).
Among countries that were represented in population-based studies, 29% of HICs and 35% of countries with Very High HDI were only represented in multinational papers compared with 75% of those in lower World Bank income categories and 77% of those in the three lower ranges of HDI.
3.6 Coverage of cancer types in included publications
Among all 303 included publications, 84 (28%) covered all cancer types, 60 (20%) were devoted to leukemia and lymphomas, 63 (21%) were devoted to CNS tumors, 74 (24%) were restricted to all or part of a single ICCC-3 main group of non-CNS solid tumors, and 22 (7%) covered a wide range of combinations of cancers, sometimes defined by primary site rather than morphology.
4 Discussion
This review confirms that population-based survival estimates of childhood cancer in the 21st century are available for many affluent countries, although quite often not for all of the principal diagnostic groups. Information is relatively scarce for less well-resourced countries. In many countries it has only been possible to estimate survival for some regions, which may not be representative of the whole country.
The first requisite for calculating cancer survival at the population level is population-based case ascertainment, virtually always by a PBCR. Institutional (including multi-institutional) series often contain richer clinical information than is found in most PBCRs and can yield much valuable information about cancer within a defined population, especially when they contain large numbers of cases (70). However, they necessarily exclude patients from that population who are diagnosed and treated (or remain untreated) outside the participating institutions, and survival estimated from their data will likely be biased upwards compared with the true result in the entire target population.
The second requisite is knowledge of the vital status of individual patients at given time intervals since diagnosis. A large number of countries, predominantly those in the lower categories of per capita income and HDI, are without population-based cancer registration even at sub-national level (Table 2). But even when there is population-based registration of incident cases, follow-up for vital status is not always straightforward. The most efficient method of obtaining this information is passive follow-up by linkage to death registrations, but an acceptable level of accuracy is only achievable if there is a high percentage completeness of death registration in the population. Moreover, for follow-up by a sub-national cancer registry, death registration should ideally be complete not merely within the registry's own territory but nationally, to allow for internal migration. The absence of complete death registration is also more often a feature of less well-resourced countries (Table 2), and follow- up by active tracing of patients becomes necessary. In a recent study of cancer in adults, for example, passive follow-up by linkage with national death registration was possible in only one out of 13 participating PBCRs from Sub-Saharan Africa (71). Active follow-up not only has varying degrees of success, it is also labor intensive, straining already scarce resources. Presumably for this reason, in a study of childhood cancer survival from three PBCRs in Sub-Saharan Africa, active follow-up was carried out by one of the participating registries only for a random sample of patients rather than for the entire patient population (64).
The numerous single-country studies included in this review have made substantial contributions to knowledge concerning population-level survival of children with cancer within their own countries. Multinational studies, however, whether the product of ad hoc collaborations involving a few countries or established consortia of much larger numbers of countries, have several important advantages. They pool data processing and analytical resources which may be scarce in some participating countries. The use of common definitions, data validation standards and procedures, outcome measures, and analytical methods enhances comparability between results for individual countries or for larger groups of countries based on factors including geography, socioeconomic indicators and characteristics of healthcare systems. The contrasts in the proportions of countries represented only in multinational studies between HICs and those in lower income categories and between countries with Very High HDI and those with a lower HDI show that multinational studies present especially valuable opportunities to less well-resourced countries for their results to be made visible and available for comparison.
There should generally be a high degree of comparability of ostensibly similar diagnostic categories between studies because of the widespread use of ICCC-3, other systems defined in terms of ICD-O-3, and ICD-O-3 itself. There are, however, two points on which there may be systematic differences between datasets. The first is uncertainty in most instances as to whether the overall category of all cancers includes skin carcinomas or non-melanoma skin cancer, but this is unlikely to have a substantial influence on survival rates for all cancers combined because these tumors are rare among children (72). More problematic is the continuing exclusion of CNS tumors with non-malignant behavior codes by some PBCRs, although increasing numbers of registries do include non-malignant intracranial and intraspinal tumors. The effect of excluding non-malignant tumors of these sites became more severe when pilocytic astrocytoma, the most frequent of childhood CNS tumors, was downgraded to uncertain behavior in ICD-O-3, having been regarded as malignant in earlier editions of ICD-O. Survival rates could in principle be compared between registries that include non-malignant CNS tumors and those that exclude them by restricting the comparison to malignant tumors, but such comparisons could still be unreliable because astrocytoma, not otherwise specified, is still assigned a malignant behavior code and it is impossible to know how many astrocytomas of unspecified subtype are in fact pilocytic (40, 73). International comparison of survival rates for CNS tumors, whose overall frequency is second only to that of leukemias, would be greatly simplified if non-malignant tumors of intracranial and intraspinal sites were routinely ascertained and followed up by all PBCRs.
The World Health Organization's Global Initiative for Childhood Cancer has the target of achieving 60% survival globally for children and adolescents with cancer by the year 2030, and wider availability of robust information on survival at population level will be essential for monitoring progress toward this goal (74). Reliable population-based information is available and extensively published from a large proportion of the most affluent countries, where 5-year survival is already well above 60%. Increasing the coverage and quality of cancer registration and death notification in as many lower-resource countries as possible would in turn increase the volume and geographic spread of the raw data from which survival rates can be estimated for those countries. International collaborations will continue to play a vital part in enabling comparison of childhood cancer survival between populations with confidence that the results are underpinned by uniform procedures for data validation and analysis.
Data availability statement
Publicly available datasets were analyzed in this study. This data can be found at: https://pubmed.ncbi.nlm.nih.gov/, https://clarivate.com/academia-government/scientific-and-academic-research/research-discovery-and-referencing/web-of-science/, https://www.cia.gov/the-world-factbook/field/age-structure, https://datahelpdesk.worldbank.org/knowledgebase/articles/906519-world-bank-country-and-lending-groups, and Human Development Reports. Human Development Index. (2022) https://hdr.undp.org/data-center/human-development-index#/indicies/HDI.
Author contributions
CS: Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Project administration, Writing – original draft, Writing – review & editing.
Funding
The author(s) declare that no financial support was received for the research and/or publication of this article.
Conflict of interest
The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Generative AI statement
The author(s) declare that no Gen AI was used in the creation of this manuscript.
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Appendix
PubMed search strategy
(infant, newborn[mh] OR newborn Infant*[tw] OR newborn*[tw] OR neonate*[tw] OR infant[mh] OR infan*[tw] OR child[mh] OR child*[tw] OR pediatric[tw] OR paediatric[tw])
AND
(neoplasms[mh] OR neoplas*[tw] OR tumor*[tw] OR tumour*[tw] OR cancer*[tw] OR malignan*[tw] OR benign neoplasm*[tw] OR leukaemia[tw] OR leukemia[tw] OR lymphoma[tw] OR sarcoma[tw] OR carcinoma[tw])
AND
(survival rate[mh] OR survival rate*[tw])
AND
nationwide[tw]
Web of Science search strategy
TS=((infants, newborn OR newborn infant* OR newborn* OR neonate* OR infant* OR child*)
AND
(neoplas* OR tumo$r* OR cancer* OR malignan* OR benign neoplasm*)
AND
(survival* OR survival stud* OR studies, survival OR survival rate*)
AND
(registr* OR population registr* OR population based OR populational based))
Keywords: childhood cancer, leukemia, survival, population-based, cancer registry, international
Citation: Stiller CA (2025) Global population-based childhood cancer survival in the 21st century: a scoping review. Front. Cancer Control Soc. 3:1572317. doi: 10.3389/fcacs.2025.1572317
Received: 06 February 2025; Accepted: 14 July 2025;
Published: 11 August 2025.
Edited by:
Vesna Zadnik, Institute of Oncology Ljubljana, SloveniaReviewed by:
Stefan Heinze, Nova Scotia Health Authority, CanadaJaime Shalkow, Cancer Center, ABC Medical Center, Mexico
Copyright © 2025 Stiller. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Charles A. Stiller, Y2hhcmxlcy5zdGlsbGVyMUBuaHMubmV0