In 2022, an estimated 18.1 million people in the United States were living with a history of cancer. Among them was a population that barely existed at meaningful scale a generation ago: people who survived cancer diagnosed during childhood or adolescence. As of 2020, nearly 496,000 cancer survivors in the United States had first been diagnosed before the age of 20.[1]
Their presence in those numbers is, in one sense, a triumph of modern oncology. Today, about 85% of children diagnosed with cancer are alive at least five years after diagnosis, and many will ultimately be considered cured.[1] But five-year survival answers only one question: whether a child lived through the immediate threat of cancer. It says much less about what happens at 25, 40, or 60—decades after the last dose of chemotherapy, a biologic, or the final radiation treatment. That question, largely invisible in headline survival statistics, is the subject of one of the longest-running and most influential research efforts in childhood cancer: the Childhood Cancer Survivor Study (CCSS).
When Survival Creates a New Kind of Patient
The medicines and treatment protocols that cured a growing share of childhood cancers were, for decades, developed with one overriding goal: keeping the child alive. Less attention, by necessity, could be given to what those same treatments might mean for a body that still had decades of life ahead.
Surgery, radiotherapy, chemotherapy, and hematopoietic stem cell transplantation can leave effects that do not become apparent until years after treatment has ended. These delayed consequences are generally referred to as late effects and can range from endocrine, reproductive, cardiovascular, pulmonary, neurocognitive, and musculoskeletal problems to subsequent cancers.[2] The National Cancer Institute (NCI) describes late effects as health problems that develop years after cancer treatment and notes that their occurrence depends on factors including the original cancer, age at treatment, and the type and intensity of therapy.[2]
For childhood cancer survivors, that long interval matters. A treatment that is lifesaving at age 7 may have consequences that do not become clinically apparent until the survivor is 30 or 40 years of age. The growing population of survivors has therefore created a medical question that pediatric oncology did not have to confront on the same scale in earlier generations: How do we make sure that surviving cancer also means having the best possible health for the rest of life?
Three Decades, Two Cohorts, One Study
The Childhood Cancer Survivor Study was established in 1994 with funding from the NCI and other organizations. The study was created to better understand late effects, improve survival, and reduce the harmful consequences of cancer treatment.[3] The original Childhood Cancer Survivor Study cohort enrolled survivors diagnosed between 1970 and 1986 at participating centers in the United States and Canada. More than 14,000 survivors were followed, along with approximately 4,000 siblings who served as a comparison group.[3]
However, as childhood cancer treatment changed, researchers expanded the study to include survivors diagnosed between 1987 and 1999, along with additional siblings. The expanded cohort was designed in part to capture the effects of newer treatment approaches and different patterns of exposure.[3] Today, the combined Childhood Cancer Survivor Study resource includes more than 25,000 survivors diagnosed between 1970 and 1999, enabling the study of health outcomes across different treatment eras.[4]
That longitudinal perspective is one of the study’s greatest strengths. Researchers can connect a survivor’s later health to the treatments received years earlier rather than treating childhood cancer survivors as a single, undifferentiated group. The distinction matters. A child treated with surgery alone is not exposed to the same risks as a child who received high-dose anthracyclines, cranial irradiation, chest radiation, or a stem cell transplant. The Childhood Cancer Survivor Study has provided the scale and treatment information needed to begin separating those risks.
What Three Decades of Follow-Up Have Found
The Childhood Cancer Survivor Study has not produced one defining discovery. Instead, decades of follow-up have gradually revealed where treatment-related risks emerge—and how those risks differ from one survivor to another. Researchers have identified increased risks of subsequent cancers, cardiovascular disease, endocrine and reproductive problems, pulmonary complications, and other chronic health conditions among childhood cancer survivors.[2][5]
The study has also helped establish important treatment-specific relationships. Radiation exposure, for example, has been associated with subsequent cancers involving the breast, thyroid, central nervous system, bone, soft tissue, and skin.[5] Other analyses have documented treatment-related cardiovascular and reproductive risks. The result is a more detailed picture of survivorship. A cancer survivor is not simply someone who has finished treatment. Their future health may still be influenced by the treatment exposures they experienced years or even decades earlier. That evidence has helped inform the Children’s Oncology Group (COG) Long-Term Follow-Up Guidelines, which provide recommendations for screening and follow-up based on a survivor’s cancer and treatment history.[6]
For a primary care physician who may see only a small number of childhood cancer survivors, that treatment history can be critical. Knowing that a patient received chest radiation, for example, can change the physician’s understanding of the patient’s long-term risk and the appropriate surveillance.
How Much Risk, and to Whom: A JAMA Review
A 2023 review by Smita Bhatia, Emily S. Tonorezos, and Wendy Landier in JAMA brought much of the survivorship evidence together into a clinical framework.[7] The authors estimated that approximately 500,000 people currently living in the United States have survived childhood cancer. By age 45, approximately 95% of people who survive childhood cancer will have developed a significant health problem related to their childhood cancer diagnosis or its treatment.[7]
The burden is not distributed evenly.
Among severe or life-threatening chronic health conditions reported in the review, endocrine disorders—including hypothyroidism and growth hormone deficiency—were the most common category, accounting for 44%. Subsequent neoplasms accounted for 7%, while cardiovascular disease—including cardiomyopathy, congestive heart failure, coronary artery disease, and cerebrovascular disease—accounted for 5.3%.[7] Some groups face substantially greater risks than others. Survivors of childhood brain cancer who received cranial irradiation have an approximately 70% prevalence of severe or life-threatening health problems, while the corresponding figure for survivors who received an allogeneic hematopoietic stem cell transplant is approximately 60%.[7]
At the other end of the spectrum are survivors of some solid tumors, including Wilms tumor, who were treated with surgery alone or minimal chemotherapy. Their prevalence of subsequent health problems can be similar to that of people who did not have cancer during childhood or adolescence.[7] The difference is a reminder that childhood cancer survivor is not a single risk category. The original diagnosis, treatment exposures, age at treatment, and other factors all matter.
The implications extend beyond morbidity. A Childhood Cancer Survivor Study-based analysis published in JAMA Oncology found that projected life expectancy has improved for survivors treated in more recent decades. For five-year survivors diagnosed during 1970–1979, the projected life expectancy gap relative to the general population was 16.5 years. That gap narrowed to 12.3 years for those diagnosed during 1980–1989 and 9.2 years for those diagnosed during 1990–1999.[8]
The improvement is encouraging, but it is also a reminder of how much remains to be done. Even among survivors treated in the 1990s, the analysis projected a shorter lifespan than that of people without a childhood cancer history.[8]
From Observation to Intervention
The Childhood Cancer Survivor Study was designed not simply to describe late effects but to provide an evidence base for reducing them. That transition—from observation to intervention—is an important part of the study’s history. Once researchers could identify survivors at elevated risk, they could begin asking a different question: Can we change what happens next?
Intervention studies using the Childhood Cancer Survivor Study resource have examined approaches to cardiovascular health, breast cancer screening, skin cancer screening, smoking cessation, physical activity, health insurance navigation, and other aspects of survivorship care.[9] Some of these studies focus on helping survivors engage with recommended screening. Others address modifiable risk factors that can compound treatment-related risks.
The current Childhood Cancer Survivor Study intervention portfolio includes studies such as the Evaluation of Cardiovascular Health Outcomes among Survivors 2 (ECHOS-2; NCT07245420), the Survivors Engaged in Time-Restricted EatiNG After THerapy study (STRENGTH; NCT07009288) examining cardiometabolic risk,[9] the Health Insurance Navigation Intervention Trial, and the Study of Active Lifestyle Activation.[10][11] The significance is greater than that of any single intervention. The Childhood Cancer Survivor Study has evolved from a cohort documenting what happens to survivors into a research infrastructure that can help test ways to improve what happens to them next.
The Larger Landscape Behind the Cohort
The story of the Childhood Cancer Survivor Study is inseparable from the broader progress made against pediatric cancer. According to the American Association for Cancer Research (AACR) Pediatric Cancer Progress Report 2025, the five-year survival rate for all pediatric cancers combined in the United States increased from 63% in the mid-1970s to 87% among children and adolescents diagnosed between 2015 and 2021.[10] Pediatric cancer mortality has also fallen substantially. The AACR report estimates a 57% decline in pediatric cancer mortality between 1970 and 2000, followed by a further 19% decline between 2001 and 2023.[12]
Treatment has changed as well. Between 2015 and 2025, the U.S. Food and Drug Administration approved more than 20 molecularly targeted therapies and more than 10 immunotherapies for pediatric cancers.[12] Those advances have changed what survival means. But they have not changed it equally for every child. Survival now exceeds 90% for some pediatric cancers, including Hodgkin lymphoma, thyroid carcinoma, and retinoblastoma. At the same time, certain aggressive brain tumors and sarcomas continue to have poor outcomes.[12]
The disparities are also not limited to tumor biology. The AACR report highlights differences in outcomes associated with race, ethnicity, geography, and socioeconomic circumstances, as well as major disparities between high-income and low- and middle-income countries.[12] A recent study of Wilms tumor in the United Kingdom and Ireland illustrates the progress that can be achieved in a cancer with generally favorable outcomes while also showing why risk stratification remains important. The IMPORT study followed 620 patients diagnosed between 2012 and 2022. Five-year survival was generally above 90%, but survival varied substantially by tumor stage and histologic risk, with high-risk histology associated with the greatest excess risk of death.[13]
That combination—dramatic overall progress alongside persistent high-risk groups—is part of the environment in which survivorship research operates. More children are surviving. More of them are living for decades after treatment. And as the survivor population grows, the consequences of treatment become an increasingly important part of cancer care itself.
What Remains to Be Learned
The Childhood Cancer Survivor Study also has an important limitation. Its survivors were diagnosed and treated between 1970 and 1999.[3][4] That means the study provides an extraordinary window into long-term outcomes after earlier generations of pediatric cancer treatment, but it cannot yet tell us everything about the consequences of therapies introduced or widely adopted more recently. Molecularly targeted therapies, newer immunotherapies, cellular therapies, and increasingly precise radiation techniques are changing pediatric cancer treatment. Their long-term effects may be different from those associated with the therapies used in the original Childhood Cancer Survivor Study cohorts.
This creates an unavoidable time lag. Researchers cannot know today what a treatment given to a child in 2026 will mean for that person’s health at age 50. Those answers require decades of follow-up. The history of the Childhood Cancer Survivor Study also illustrates why that long-term perspective matters. The study has already shown that treatment-associated morbidity and mortality can persist long after cancer treatment has ended—and that changes in treatment can alter those risks over time.[2][8] It is also important to be precise about what survivorship guidelines can and cannot claim.
As Bhatia and colleagues noted in a 2024 JAMA reply, no randomized clinical trial has tested the efficacy of the COG Long-Term Follow-Up Guidelines in reducing adverse treatment-related outcomes. That limitation applies across the guidelines, not simply to skin cancer screening.[14]
The reason is as much practical as it is scientific. Individual late effects may be relatively uncommon, while the interval between treatment and the development of a complication can span decades. Conducting a randomized trial large enough and long enough to demonstrate the effect of a specific screening recommendation would be extremely difficult. The recommendations therefore combine evidence about which survivors are at risk with expert consensus about how those survivors should be screened.[14] That distinction does not make the guidelines unimportant. It simply more accurately defines the evidence supporting them.
A Growing Population, and a Longer Conversation
Each September, Childhood Cancer Awareness Month turns public attention toward the children and adolescents diagnosed with cancer each year—and toward the families facing the immediate realities of diagnosis and treatment.
But there is another story that deserves equal attention. It is the story of the hundreds of thousands of people who survived childhood cancer and are now living well beyond their original diagnosis.[1] For many, the cancer itself is no longer the central medical issue. Their questions may instead involve heart health, fertility, endocrine function, second cancers, mental health, physical function, or simply understanding what their childhood treatment means for the decades ahead.[2][7]
That is the paradox at the heart of modern childhood cancer care: more children are surviving, but survival has created a much larger population living with the consequences of treatment. The Childhood Cancer Survivor Study has helped medicine recognize that reality and begin to quantify it. It has linked treatment exposures to long-term outcomes, helped identify survivors at greatest risk, informed survivorship guidelines, and provided a foundation for interventions intended to improve survivors’ health and quality of life.[3][6][9]
The next generation of survivorship research will have to answer a new question. What happens to children treated with today’s increasingly targeted and less toxic therapies when they reach middle age?
That answer will take time.
But the lesson from CCSS is already clear: “cured” cannot simply be a five-year milestone. It should describe the possibility of a full, healthy life long after cancer treatment ends.
Clinical trials
Evaluation Of Cardiovascular Health Outcomes Among Survivors 2 – ClinicalTrials.gov ID NCT07245420
A Study of Time-Restricted Eating in Childhood Cancer Survivors ClinicalTrials.gov ID NCT07009288
Related Resources
[1] National Cancer Institute. Childhood Cancer Survivor Study: An Overview. [Article] Last accessed on September 2, 2026
[2] National Cancer Institute. Late Effects of Treatment for Childhood Cancer (PDQ). [Online] Last accessed on September 2, 2026
[3] National Cancer Institute. Childhood Cancer Survivor Study: [Dataset]. Last accessed on September 2, 2026
[4] National Cancer Institute. Childhood Cancer Survivor Study clinical study information.
[5] Robison LL, Armstrong GT, Boice JD, Chow EJ, Davies SM, Donaldson SS, Green DM, Hammond S, Meadows AT, Mertens AC, Mulvihill JJ, Nathan PC, Neglia JP, Packer RJ, Rajaraman P, Sklar CA, Stovall M, Strong LC, Yasui Y, Zeltzer LK. The Childhood Cancer Survivor Study: a National Cancer Institute-supported resource for outcome and intervention research. J Clin Oncol. 2009 May 10;27(14):2308-18. doi: 10.1200/JCO.2009.22.3339. Epub 2009 Apr 13. PMID: 19364948; PMCID: PMC2677920.
[6] DeVine A, Landier W, Hudson MM, Constine LS, Bhatia S, Armenian SH, Gramatges MM, Chow EJ, Friedman DN, Ehrhardt MJ. The Children’s Oncology Group Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers: A Review. JAMA Oncol. 2025 May 1;11(5):544-553. doi: 10.1001/jamaoncol.2024.6812. Erratum in: JAMA Oncol. 2025 May 1;11(5):570. doi: 10.1001/jamaoncol.2025.1484. PMID: 39976936; PMCID: PMC12188901.
[7] Bhatia S, Tonorezos ES, Landier W. Clinical Care for People Who Survive Childhood Cancer: A Review. JAMA. 2023 Sep 26;330(12):1175-1186. doi: 10.1001/jama.2023.16875. PMID: 37750876.
[8] Yeh JM, Ward ZJ, Chaudhry A, Liu Q, Yasui Y, Armstrong GT, Gibson TM, Howell R, Hudson MM, Krull KR, Leisenring WM, Oeffinger KC, Diller L. Life Expectancy of Adult Survivors of Childhood Cancer Over 3 Decades. JAMA Oncol. 2020 Mar 1;6(3):350-357. doi: 10.1001/jamaoncol.2019.5582. PMID: 31895405; PMCID: PMC6990848.
[9] Cares K, Lima Oliveira M, Bryner A, Man B, Chen Z, Bernabé BP, Schmidt ML, Fitzgibbon M, Gabel K. Time-Restricted Eating and Prebiotic Supplementation Demonstrate Feasibility and Acceptability in Young Adult Pediatric Cancer Survivors: A Randomized Controlled Pilot Trial. Nutrients. 2025 Oct 21;17(20):3306. doi: 10.3390/nu17203306. PMID: 41156558; PMCID: PMC12567023.
[10]Park ER, Kirchhoff AC, Donelan K, Perez GK, McDonald A, Bliss CC, Foor A, van Thiel Berghuijs KM, Waters AR, Durieux N, Leisenring W, Armstrong GT, Ponzani C, Lopez A, Vaca Lopez PL, Battaglia T, Galbraith AA, Kuhlthau KA. Health Insurance Navigation Tools Intervention: A Pilot Trial Within the Childhood Cancer Survivor Study. JCO Oncol Pract. 2024 Jul;20(7):953-963. doi: 10.1200/OP.23.00680. Epub 2024 Mar 12. PMID: 38471048; PMCID: PMC11292596.
[11] Childhood Cancer Survivor Study. Intervention Studies. (Published Studies)
[12] American Association for Cancer Research. AACR Pediatric Cancer Progress Report 2025. [Report]
[13] Ssenyonga N, Lopez-Cortes A, Al-Saadi R, Tugnait S, Dzhuma K, Duncan C, Vujanic G, Chowdhury T, Allemani C, Coleman MP, Pritchard-Jones K; Children’s Cancer and Leukaemia Group (CCLG) Renal Tumour Special Interest Group. Survival for Children Diagnosed With Wilms Tumour (2012-2022) Registered in the UK and Ireland Improving Population Outcomes for Renal Tumours of Childhood (IMPORT) Study. Pediatr Blood Cancer. 2026 Mar;73(3):e70061. doi: 10.1002/1545-5017.70061. Epub 2026 Jan 16. PMID: 41540889.
[14] Bhatia S, Tonorezos ES, Landier W. Survival of Childhood Cancer and Subsequent Clinical Care-Reply. JAMA. 2024 Feb 20;331(7):617. doi: 10.1001/jama.2023.26984. PMID: 38497699.
This article is intended for informational purposes for healthcare professionals and does not constitute medical advice. Survivors and families with questions about individual risk for late effects following childhood cancer treatment should consult a physician familiar with their treatment history, ideally through a long-term follow-up or survivorship clinic.
Featured image: © Licensed under the Unsplash+ License. Used with permission.
DOI
