A groundbreaking international study collaboration spearheaded by researchers from University College London (UCL) and the Fondazione IRCCS Istituto Nazionale dei Tumori in Milan (INT) has, for the first time, delineated the extent of childhood cancer spread at diagnosis in a manner that facilitates robust comparison across nations. This landmark investigation sheds new light on the longstanding puzzle of why survival rates in children’s cancer differ so markedly between countries, highlighting tumor stage at diagnosis as a crucial explanatory factor for these disparities.
While it has been long understood that survival tends to worsen with later-stage diagnoses, this study, published in the prestigious JAMA Network Open, represents the first comprehensive population-based analysis linking tumor progression at diagnosis with survival discrepancies at an international level. Using meticulously curated and high-caliber data from nearly 10,000 pediatric cases spanning 73 cancer registries and 27 countries, the research team scrutinized six common childhood cancers: neuroblastoma, Wilms tumor, medulloblastoma, osteosarcoma, Ewing sarcoma, and rhabdomyosarcoma, which collectively represent a significant proportion of childhood solid tumors.
The team’s analysis revealed a compelling trend across these diverse cancer types—survival probability at three years post-diagnosis decreased progressively with advancing tumor stage. Employing Central Europe—a region comprising Austria, Belgium, France, Germany, Switzerland, and the Netherlands—as a benchmark, the study illuminated pronounced regional disparities in three-year survival for four of the six cancers assessed. This regional variability opens important avenues for targeted interventions and health system improvements.
In particular, the outcomes for neuroblastoma—a cancer typically originating in the adrenal glands or related neural tissues—were striking. Children diagnosed in the United Kingdom and Ireland experienced significantly lower survival rates compared to their Central European counterparts. Critically, this survival gap aligned closely with a pattern of delayed diagnosis and more advanced tumor stages at presentation in the UK and Ireland. These findings provide empirical confirmation that efforts to expedite neuroblastoma diagnosis could materially enhance survival outcomes in these regions.
Conversely, the survival disparities for Ewing sarcoma, a malignancy of the bone and soft tissues, presented a more intricate picture. Both Eastern Europe and the UK/Ireland displayed inferior survival relative to Central Europe, yet these differences persisted even after adjusting for tumor stage at diagnosis. Indeed, lower survival was chiefly observed in cases where the tumor had already metastasized. This suggests that factors beyond diagnostic timeliness—such as biological differences in metastatic spread, the sites affected, and potential variations in treatment protocols—may influence survival outcomes, underscoring the complexity of cancer care delivery and patient biology.
The significance of this study extends beyond merely cataloguing disparities; it addresses a critical prior limitation in pediatric oncology epidemiology. Historically, a lack of standardized, high-quality data regarding tumor stage at diagnosis hampered the ability to conduct reliable international survival comparisons. The BENCHISTA project, an international benchmarking initiative underpinning this research, has revolutionized childhood cancer registry data collection by harmonizing staging data using the Toronto Childhood Cancer Stage Guidelines, which standardize definitions of tumor progression. Achieving at least 90% stage completeness per country—a threshold deemed sufficient for robust intercountry analysis—required negotiation and cooperation among 23 European nations and collaborators from Brazil, Canada, Australia, and Japan.
By enabling consistent and reliable tumor staging data collection, BENCHISTA provides an unprecedented global lens through which pediatric oncologists, policymakers, and researchers can better understand survival disparities. Identification of later-stage diagnosis as a major contributor to poorer outcomes in some cancers, such as neuroblastoma, empowers the design of cancer-specific strategies aimed at earlier detection and diagnostic precision. However, for tumors like Ewing sarcoma where stage alone does not account for survival differences, the findings pave the way for investigations into subsequent treatment accessibility, protocols, and systemic health care disparities.
In addition to solidifying the connection between tumor stage and survival, the study points to the necessity of examining wider systemic and clinical factors. Variability in therapeutic regimens, access to specialized childhood cancer services, and differences in health systems’ capacity and coordination may all underlie remaining survival discrepancies. The BENCHISTA consortium intends to pursue these lines of inquiry in the study’s next phase, which will include analysis of five-year survival, a more established benchmark for cancer epidemiological outcomes.
The authors emphasize that their findings supply unbiased, population-level evidence that earlier diagnosis—while vital—is insufficient on its own to eradicate survival inequalities. For instance, in the UK and Ireland, later diagnosis clearly compromises survival in neuroblastoma, yet for Ewing sarcoma, tailored treatment approaches for advanced cases likely play a pivotal role in improving outcomes. Such nuanced insights underscore the importance of both diagnostic and therapeutic advancements in pediatric oncology.
The leadership involved in the study highlights the multidisciplinary cooperation necessary for such an undertaking. Professor Kathy Pritchard-Jones of UCL’s Great Ormond Street Institute of Child Health remarked that this international effort has unveiled critical insights into why survival disparities persist, pointing to the importance of putting these findings into practical policy and clinical context. Likewise, Dr. Laura Botta, the project’s corresponding author, underlined the imperative of ongoing collaboration between clinicians and registry experts to maintain and enhance data quality, enabling continuous improvements in childhood cancer care worldwide.
In addition to clinical and epidemiological ramifications, the BENCHISTA study reverberates on a humanitarian level. Patient and public involvement representatives, such as Angela Polanco whose daughter survived Wilms tumor, stress that access to timely diagnosis and expert care should be a universal standard, irrespective of geography. Accurate and comprehensive data collection at the population level is crucial in recognizing and rectifying health inequalities, ultimately leading to better survival rates and quality of life for children with cancer.
The study’s use of large-scale registry data highlights modern epidemiologic approaches in rare diseases, overcoming challenges of small sample sizes through multinational cooperation. While the three-year follow-up period may not capture all long-term survival outcomes, the sizeable cohort and rigorous data harmonization establish a valuable foundation for future research and healthcare improvements.
Collectively, these findings not only point to the necessity of implementing cancer-specific early detection programs but also advocate for systemic reforms that encompass uniform staging procedures, equitable treatment access, and comprehensive supportive care infrastructure. With childhood cancer survival rates still varying across borders, this international study provides a data-driven roadmap for closing these gaps and realizing the vision that every child, regardless of where they live, has the best possible chance of survival and thriving beyond cancer.
Subject of Research: People
Article Title: Stage at Diagnosis and International Survival Variation in Childhood Tumors in the BENCHISTA Study
News Publication Date: 9-Feb-2026
Web References: https://dx.doi.org/10.1001/jamanetworkopen.2025.56747
