Why Childhood Cancer Is Different: From Diagnosis to Recovery

By Dr. Luis Vaschetto, Ph.D.Reviewed by Lauren Hardaker

Childhood cancers arise from unique developmental processes and demand treatments that balance cure with lifelong well-being. Survivors face significant lifelong health risks, making coordinated, equitable, and development-aware care essential. 

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Introduction

Childhood cancer presents a significantly different challenge compared to adult oncology, from diagnosis to recovery. It is not a simple version of an adult disease, but a distinct entity shaped by unique biology, treatment considerations, and long-term cognitive and physical effects. The survivorship phase requires lifelong monitoring and specialized care due to the unique late effects of therapy on a child's growth and organ function. Understanding this is critical to provide effective, compassionate, and life-affirming care.

In high-income countries, more than 80 % of children with cancer now survive at least five years, yet most will develop at least one chronic health condition by mid-adulthood, and outcomes remain substantially poorer in many low- and middle-income settings, making equitable, lifelong survivorship care a central goal of pediatric oncology.^5,10,11,12

The Unique Biology of Pediatric Malignancies

The most significant distinction between pediatric and adult oncology lies in biology. Adult cancers typically arise from acquired mutations linked to lifestyle factors (e.g., smoking, diet) or environmental exposures. These tumors are often carcinomas, meaning they originate from epithelial cells in the lungs, breasts, prostate, and other organs.

In contrast, childhood cancers primarily involve developmental abnormalities or genetic predisposition, frequently related to embryonic tissues. These tumors are highly diverse and include leukemias (cancers of the blood), lymphomas, brain and central nervous system tumors, sarcomas, and embryonal tumors like neuroblastoma.^1,3,10

These biological differences translate directly into how the diseases are managed. Pediatric cancers are often fast-growing and aggressive, but they are also highly sensitive to chemotherapy and radiation. It is also important to note that these treatments may have severe side effects and can lead to death in pediatric patients.^2,7,10,11 Genomic profiling has shown that many childhood cancers carry a relatively low number of somatic mutations compared with adult tumors but are frequently driven by specific structural alterations (such as gene fusions or copy-number changes) and by germline variants in cancer-predisposition genes.^1,3 This molecular simplicity makes them unique targets for targeted therapies, even as overall research into pediatric-specific treatments continues to lag behind adult cancer research.³

Pediatric Cancer Diagnosis

Due to their rapid growth and the non-specific nature of early symptoms, diagnosis in children often occurs when the disease is at an advanced stage. Unlike adults, where screening, standardized programs already exist for common cancers, there are no routine screenings for pediatric cancers. Symptoms such as persistent fatigue, unexplained fever, and swelling are often common and can lead to diagnostic delays.^4,10

Once cancer is suspected, the diagnostic process becomes highly specialized. Because children are still growing, pediatric oncologists must minimize the invasiveness of biopsies and imaging while obtaining key diagnostic and risk-stratification information. The entire diagnostic process must define the precise type and stage of the malignancy, ensuring the subsequent treatment plan protects future development. Research into blood-, urine-, and tissue-based biomarkers and corresponding biosensors aims to support earlier and less invasive diagnosis, although most such tools are not yet part of routine clinical care.⁴

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Treatment Protocols: Aggression vs. Preservation

Pediatric treatment protocols must be characterized by a delicate balance, requiring aggressive, high-dose therapy to achieve a cure, while coupling it with all measures necessary to minimize any risk of alteration in developmental pathways.^2,7,8,9

Cure rates for many common childhood cancers are remarkably high, often exceeding 80 %, a success largely attributed to decades of participation in rigorous clinical trials.^2,5,10 For instance, the 5-year overall survival rate for acute lymphoblastic leukemia has increased from 57 % in the 1970s to up to 96 %.² However, most childhood and adolescent cancer survivors will have chronic health conditions by 40 years of age, thereby necessitating more research, healthcare, and policy-making efforts.^5,11 Despite these advances, survival for children with cancer in many low- and middle-income countries remains closer to 30 - 40 %, reflecting disparities in timely diagnosis, access to chemotherapy, radiotherapy, and supportive care.^6,7,10,12

Chemotherapy and Development

Fewer chemotherapy drugs are explicitly approved for pediatric use compared to those approved for adults. Many drugs used in children are selected from agents with established safety and efficacy in pediatric populations. Conventional multi-agent chemotherapy, therefore, remains the backbone of treatment for most childhood cancers worldwide, particularly in settings where molecularly targeted drugs and immunotherapies are not widely available.^2,6,7,10,12

However, chemotherapy is associated with significant acute and late toxicities, such as anthracycline-induced cardiomyopathy and vincristine-induced peripheral neuropathy, and multidrug resistance mechanisms in tumor cells can limit its effectiveness.^7,10,11 Global analyses also reveal significant variations in the prices of essential chemotherapy agents across countries and income groups, with important implications for access and budgeting in resource-limited healthcare systems.⁶

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Radiation and Growth

Radiation therapy in pediatric cancers is more conservative and technologically advanced to minimize long-term harm, reflecting children's vulnerability and longer life expectancy after treatment. The range of adverse events observed in children differs from that in adults, partly because their tissues are still undergoing development.⁸ For instance, radiotherapy for pediatric central nervous system tumors involves precise risk stratification and improved accuracy of treatment.⁹ Initiatives such as PENTEC and advances in conformal photon and proton techniques aim to define age- and organ-specific dose–volume constraints that reduce risks of neurocognitive, endocrine, cardiovascular, and growth-related late effects while preserving tumor control.^8,9,10,11

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Survivors of Pediatric Cancer

Long-term survivors of pediatric tumors exhibit an increased risk of diverse developmental disorders and secondary primary malignancies.^5,10,11 It has been estimated that 60 % to 90 % of childhood cancer survivors are prone to develop chronic health conditions, and 20 % to 80 % experience severe or life-threatening complications during adulthood.^10,11 These late effects are extensive and may involve:

• Cardiomyopathies
• Endocrine Dysfunctions
• Neurocognitive Impairments
• Secondary Malignancies

Cohort studies have shown that by midlife, survivors may experience a substantially higher cumulative burden of chronic health conditions than their peers, with excess deaths driven by subsequent malignant neoplasms and treatment-related cardiac and pulmonary disease.^5,11

Implementing survivorship-focused care is thus crucial to mitigate late effects for childhood cancer survivors. Addressing these issues necessitates a transition from the pediatric treatment center to clinics managed by specialists who understand the complex relationships between childhood cancer protocols and adult health challenges. Models of follow-up care now range from multidisciplinary survivorship clinics to shared-care approaches with primary care providers. Still, they must be adapted to local resources, particularly in limited-resource settings.^11,12

A Coordinated Path to Life-Affirming Care

The treatment of pediatric cancers often requires a wider, multidisciplinary team compared to adult malignancies. These include pediatric oncologists, surgeons, nurses, radiation specialists, physical and occupational therapists, psychologists, and child life specialists.

The care model must extend beyond the medical, combining the educational, psychological, and social needs of the child and the entire family unit. Effective care therefore depends on coordinated communication between oncology, primary care, rehabilitation, mental health, education services, and survivorship programs, with clear treatment summaries and follow-up plans shared across teams and over time.^5,11,12

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Conclusion

Childhood cancer is defined by its unique developmental context. From the unique molecular signatures of the tumors and the challenges of early detection to the long-term implications of life-saving treatments, every step differs from adult care.^1,3,5,10

Understanding these distinctions is crucial to advancing research, optimizing specialized care protocols, and ensuring that the high rate of survival achieved for our youngest patients translates into maintaining an optimal quality of life in all regions of the world, including those with limited resources.^10,11,12

References

1. Oliver, T., & Behjati, S. (2024). Developmental Dysregulation of Childhood Cancer. Cold Spring Harbor perspectives in medicine. DOI:10.1101/cshperspect.a041580, https://perspectivesinmedicine.cshlp.org/lookup/doi/10.1101/cshperspect.a041580.
2. Malczewska, M., Kośmider, K., Bednarz, K., Ostapińska, K., Lejman, M., & Zawitkowska, J. (2022). Recent Advances in Treatment Options for Childhood Acute Lymphoblastic Leukemia. Cancers, 14. DOI:10.3390/cancers14082021, https://www.mdpi.com/doi/10.3390/cancers14082021.
3. Sweet-Cordero, E., & Biegel, J. (2019). The genomic landscape of pediatric cancers: Implications for diagnosis and treatment. Science, 363, 1170 - 1175. DOI:10.1126/science.aaw3535, https://www.science.org/doi/10.1126/science.aaw3535.
4. Gharehzadehshirazi, A., Zarejousheghani, M., Falahi, S., Joseph, Y., & Rahimi, P. (2023). Biomarkers and Corresponding Biosensors for Childhood Cancer Diagnostics. Sensors (Basel, Switzerland), 23. DOI:10.3390/s23031482, https://www.mdpi.com/doi/10.3390/s23031482.
5. Robison, L., & Hudson, M. (2013). Survivors of childhood and adolescent cancer: life-long risks and responsibilities. Nature Reviews Cancer, 14, 61-70. DOI:10.1038/nrc3634, https://www.nature.com/articles/nrc3634.
6. Habashy, C., Yemeke, T., Bolous, N., Chen, Y., Ozawa, S., Bhakta, N., & Alexander, T. (2023). Variations in global prices of chemotherapy for childhood cancer: a descriptive analysis. eClinicalMedicine, 60. DOI:10.1016/j.eclinm.2023.102005, https://www.sciencedirect.com/science/article/pii/S258953702300024X.
7. Bo, L., Wang, Y., Li, Y., Wurpel, J., Huang, Z., & Chen, Z. (2023). The Battlefield of Chemotherapy in Pediatric Cancers. Cancers, 15. DOI:10.3390/cancers15071963, https://www.mdpi.com/doi/10.3390/cancers15071963.
8. Constine, L., Ronckers, C., Hua, C., Olch, A., Kremer, L., Jackson, A., & Bentzen, S. (2019). Pediatric Normal Tissue Effects in the Clinic (PENTEC). Clinical Oncology, 31(3), 199-207. DOI:10.1016/j.clon.2019.01.002, https://www.sciencedirect.com/science/article/pii/S0936655519300031.
9. Phuong, C., Qiu, B., Mueller, S., & Braunstein, S. (2023). Precision based approach to tailoring radiotherapy. Journal of the National Cancer Center, 3, 141 - 149. DOI:10.1016/j.jncc.2023.03.001, https://www.sciencedirect.com/science/article/pii/S2666520423000149.
10. Zahnreich, S., & Schmidberger, H. (2021). Childhood Cancer: Occurrence, Treatment and Risk of Second Primary Malignancies. Cancers, 13. DOI:10.3390/cancers13112607, https://www.mdpi.com/doi/10.3390/cancers13112607.
11. Roganović, J. (2025). Late effects of the treatment of childhood cancer. World Journal of Clinical Cases, 13. DOI:10.12998/wjcc.v13.i7.98000, https://www.wjgnet.com/2307-8960/full/v13/i7/98000.htm.
12. Noyd, D., Izurieta-Pacheco, A., Mzikamanda, R., Nakiddu, N., An, D., Souvanlasy, B., Bhalla, R., Kumar, C., Bagai, P., Semerci, R., Arpaci, T., Schroeder, K., Oyewusi, A., Moreno, F., Vásquez, L., & Fuentes-Alabí, S. (2025). Childhood Cancer Survivorship Care in Limited Resource Settings. JCO Global Oncology, 11. DOI:10.1200/go-24-00274, https://ascopubs.org/doi/10.1200/go-24-00274.

Last Updated: Nov 20, 2025