Research challenges in adolescent and young adult cancer survivor research


  • Emily S. Tonorezos MD, MPH,

    1. Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York
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  • Kevin C. Oeffinger MD

    Corresponding author
    1. Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, New York
    2. Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York
    • Memorial Sloan-Kettering Cancer Center, 300 East 66th Street, New York, NY 10065
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    • Fax: (646) 888-4923

  • The articles in this supplement represent presentations and discussions at the “International Workshop on Adolescents and Young Adults with Cancer: Towards Better Outcomes in Canada” that was held in Toronto, Ontario, March 11-13, 2010.

  • Workshop on Adolescents and Young Adults with Cancer: Towards Better Outcomes in Canada, Supplement to Cancer.


Every year in Canada and the United States, about 26,000 adolescent and young adults (AYA) between ages 15 and 29 years are diagnosed with cancer. Although the majority of AYA cancer patients will survive their primary cancer, many will develop serious health problems or die prematurely secondary to their curative cancer therapy. Much is known about the long-term health outcomes after adolescent cancer. In contrast, there remain substantial gaps in our understanding of the long-term outcomes after most young adult cancers. To optimize the health and quality of life of AYA cancer survivors and improve upon curative cancer therapy, it is essential to further investigate the long-term outcomes of this population. Before embarking upon this endeavor, it is important for the investigator and the funding agency to be cognizant about some of the unique challenges in research of AYA cancer survivors. To this end, the authors present a brief overview of some of the key research challenges, discuss the strengths and limitations of using available AYA cohorts and databases, and highlight potential future directions. Cancer 2011;117(10 suppl):2295–300. © 2011 American Cancer Society.

Every year in Canada and the United States, about 26,000 adolescent and young adults (AYA) between ages 15 and 29 years are diagnosed with cancer.1, 2 With 5-year survival rates exceeding 80%,1, 2 the number of AYA cancer survivors has grown over the past decade. Notably, a significant proportion of AYA cancer survivors will develop chronic health problems as a consequence of their cancer therapy.3 An understanding of the long-term health outcomes associated with AYA cancer and cancer therapy is essential for providing anticipatory risk-based care for survivors.4 Furthermore, an appreciation of the long-term morbidity and mortality associated with specific therapies is important when developing or refining new cancer treatment strategies. Although the body of knowledge is growing regarding long-term outcomes in survivors of adolescent cancer and some young adult cancers (eg, testicular cancer), many significant knowledge gaps impede the care of this high-risk population.

The objective of this report is to provide a brief overview of the challenges and opportunities in AYA cancer survivor research. It is noteworthy that some challenges are common to all survivorship research: Cancer treatment changes over time, cancer patients must survive for 5 years to be included in most survivor databases, and many cohorts lack minority or uninsured participants. Nonetheless, the AYA survivor population does present unique challenges. In this article, we present a brief overview of these difficulties, including cancer-specific, developmental, health care system-related research challenges and confusion arising because of overlap of terminology. We also review available cohorts and databases and future directions for research.

Challenges in AYA Survivor Research

Cancer-specific challenges

Cancer in AYA is unique in the distribution of the types that occur. Hodgkin lymphoma, melanoma, testis cancer, female genital tract malignancies, thyroid cancer, soft-tissue sarcomas, non-Hodgkin lymphoma, leukemia, brain and spinal cord tumors, breast cancer, bone sarcomas, and nongonadal germ cell tumors account for 95% of the cancers in this age group (Fig. 1).1 The frequency distribution of cancer types changes dramatically from ages 15 to 30 years, such that the pattern at the youngest age does not resemble that at the oldest age.1 Furthermore, even within this narrow age range, cancer types differ in the younger age group (ages 15-19 years) compared with the older age group (ages 20-24 years and 25-29 years) (Fig. 2).1 There is little overlap of treatment exposures across cancers, particularly for the young adult carcinomas (eg, breast, cervical, thyroid), restricting the grouping of different cancers to assess outcomes associated with specific exposures. It is important to note that most research in the AYA population, including the studies referenced in this report, include primarily adults who have survived pediatric-type cancers.

Figure 1.

Cancer incidence is illustrated in (Top) females and (Bottom) males ages 15 to 29 years in the US. Surveillance, Epidemiology, and End Results (SEER) database from 1995 to 2000 (see Bleyer A, O'Leary M, Barr R, Ries LAG, eds. Cancer Epidemiology in Older Adolescents and Young Adults 15 to 29 Years of Age, Including SEER Incidence and Survival: 1975-2000. NIH Pub. No. 06-5767. Bethesda, MD: National Cancer Institute; 20061). CNS indicates central nervous system.

Figure 2.

Cancer incidence is illustrated by primary cancer site for patients (Top) ages 15 to 19 years, (Middle) ages 20-24 years, and (Bottom) ages 25-29 years in the US. Surveillance, Epidemiology, and End Results (SEER) database from 1995 to 2000 (see Bleyer A, O'Leary M, Barr R, Ries LAG, eds. Cancer Epidemiology in Older Adolescents and Young Adults 15 to 29 Years of Age, Including SEER Incidence and Survival: 1975-2000. NIH Pub. No. 06-5767. Bethesda, MD: National Cancer Institute; 20061). CNS indicates central nervous system.

Developmental stage-specific challenges

Finding AYA survivors to participate in research can be challenging because of issues surrounding social and cognitive development in this age group. A diagnosis of cancer during the AYA years may result in a disruption in the usual developmental tasks of adolescence.5-7 For instance, a man aged 22 years who is diagnosed with cancer may find himself moving back to his parents' home and relating to them in a new, somewhat infantilizing way. The normal social development at this stage, which would be to separate from the parents and form self-identity, may be impacted. After cancer, this disruption of psychosocial development may result in failure to take responsibility for health care. It has been demonstrated that survivors who are diagnosed as adolescents have greater psychological distress and fewer positive health beliefs than survivors who are diagnosed at a younger age.8, 9 Symptoms of post-traumatic stress disorder related to the cancer experience, especially “avoidance,” have been demonstrated in AYA survivors.9 A desire to escape the trauma of the cancer experience9, 10 may mean that AYA cancer survivors do not follow-up with their health care because they are hoping to put the experience of being sick behind them. The exclusion of parents or other family members in the typical adult care visit also may be a factor keeping AYA survivors out of care.10 The AYA population is very mobile and can be difficult to track, even with considerable available resources. Therefore, as opposed to young children or older adults who have survived cancer, the AYA population may be lost to follow-up and, in fact, may not even appreciate the need for follow-up.

Health care systems challenges

AYA survivors may be missing from studies because they are not engaged in the traditional primary care system.11 In the United States, a larger proportion of AYA are uninsured than any other age group.12 Many AYA cancer survivors are not able to continue coverage under their parents' health insurance once college participation has ended.13, 14 In addition, the nature of employment in this population traditionally has meant that many AYA cancer survivors do not have access to employer-based health insurance.15 Accounting for AYA cancer survivors in the health care system and ensuring proper risk-based care in this population has been limited by these difficulties. With proposed health care reforms, some of these challenges may be ameliorated.

Challenges in terminology and attributing cancer-related morbidity

Research in AYA cancer survivors has been hindered by a confusion of clinical and research terminology. Two terms describe the morbidity of cancer survivors: long-term effects and late effects.16 Conditions that develop during therapy and persist after completion of therapy are referred to as long-term effects. In contrast, conditions that develop after the completion of therapy are referred to as late effects. Other terms that have been used in the literature to describe health outcomes of survivors include side effects of therapy (late occurring), late toxicities, and late sequelae.

Furthermore, without detailed, prospective evaluation, it can be difficult to determine whether a condition developed during therapy or after therapy was completed. For example, subtle neurocognitive deficits may be evident during therapy but may become more apparent clinically after the completion of treatment. Thus, some may label a neurocognitive deficit as a long-term effect, whereas others would code it as a late effect.

Finally, some health problems after AYA cancer are not related to the cancer or its treatment and simply reflect the normal aging process and the genetic/lifestyle predispositions of the individual. In an individual with no other risk factors or comorbid conditions, it is relatively easy to associate anthracycline exposure with a cardiomyopathy. For example, in a testicular cancer survivor aged 40 years who is 20 years off therapy, it is difficult to ascertain whether his new-onset hypertension is related to his previous cisplatin exposure. Therefore, in AYA cancer survivorship research, comparison with noncancer populations is essential.

Grading the severity of late effects can provide much more information than simply reporting the prevalence of an outcome. The Common Terminology Criteria for Adverse Events (version 3) is a scoring system that was developed with the National Cancer Institute by a multidisciplinary group and was intended for use in scoring both acute and chronic conditions for cancer patients and survivors of all ages.17, 18 There are 5 grades: grade 1, mild; grade 2, moderate; grade 3, severe; grade 4, life-threatening or disabling; and grade 5, death. This scoring system also can be used to grade chronic conditions in a comparison group.

Available Cohorts and Registries for Study

There are a few populations of AYA cancer survivors that can be used in studies assessing long-term health outcomes. Below is a brief discussion of the strengths and limitations of these sources.

Cancer registries

The US Surveillance, Epidemiology, and End Results (SEER) and European population-based cancer registries can be used to assess late mortality and second cancers. This approach has provided risk estimates for second cancers among AYA groups, including Hodgkin lymphoma,19, 20 non-Hodgkin lymphoma,21 and testicular cancer survivors.22 From the SEER data, Bleyer et al published a seminal monograph on AYA cancer epidemiology.1 However, the detail of treatment information in these registries is limited to yes/no radiation or yes/no chemotherapy. Data are collected routinely only for mortality and second cancers (and not for cardiac disease or other important outcomes) through the registries. Without the expenditure of additional resources, observations are limited to cancer groups and crude treatment exposures. It is noteworthy that case-control studies formulated from registries can lead to major advances in our understanding of second cancers, as illustrated by the work of Travis et al.23, 24

Clinical trial cooperative groups

Clinical trial cooperative groups (eg, Children's Oncology Group, Southwest Oncology Group) are potentially useful for determining the prevalence of early occurring late effects among survivors of AYA cancer. Detailed treatment information is collected along with sociodemographic data. However, because the loss-to-follow-up rate beyond 5-years is high, studies assessing later occurring outcomes can be very difficult to conduct and result in potentially biased findings. Also, additional resources are needed if a noncancer comparison population is warranted by the study aims.

Childhood Cancer Survivor Study

The Childhood Cancer Survivor Study (CCSS) is a 26-institution, retrospectively ascertained, longitudinal cohort study that is following over 14,000 long-term survivors of childhood and adolescent cancer from the United States and Canada who were diagnosed with cancer from 1970 to 1986 and a similarly aged cohort of 3600 noncancer siblings.25 The CCSS includes a large, geographically and socioeconomically diverse cohort of survivors who were diagnosed with cancer during adolescence and early young adulthood between ages 15 and 20 years. Expansion of the CCSS to include long-term survivors diagnosed from 1987 to 1999 is ongoing.

The cornerstone of the CCSS is the detailed cancer and cancer therapy information that was abstracted by the participating institutions. Use of this information has allowed investigators to establish radiation dose-response relations for several radiation-induced cancers.26-28 Although most outcomes are self-reported, the incidence and severity of outcomes appear similar to those ascertained through clinical examination.17, 29, 30

Canadian provincial registry linkages

In British Columbia, McBride and colleagues have assembled a cohort of all 5-year survivors of a cancer diagnosed before age 25 from 1970 to 1995 through the Childhood/Adolescent/Young Adult Cancer Survivors (CAYACS) Research Program. Population sample comparison groups were drawn from provincial registries, and these records have been linked to provincial administrative datasets.31 A similar effort to link multiple administrative databases is underway through the Pediatric Oncology Group of Ontario (POGO).

Future Research in AYA Cancer Survivors

Of primary importance in AYA cancer survivor research is the ongoing effort to improve cancer outcomes in this age group. For many diagnoses, AYA patients have not experienced ongoing gains in survival, as noted above. Oncologists and other caregivers specializing in this age group are needed. In terms of AYA survivor research, and as described above, studies should include noncancer populations to be of greatest benefit. Areas that are ripe for research in this population include barriers to care, racial/ethnic differences in late effects, psychological and economic late effects, and research in medical late effects, such as cardiovascular toxicity after cisplatin for testicular cancer.

Opportunities for AYA Cancer Survivor Research in Canada

Through the use and expansion of provincial cancer registries and data linkages, Canada is positioned to make major contributions to our understanding of the outcomes after AYA cancer. In a first step, additional grant support would allow expansion of the CAYACS and POGO cohorts to include survivors throughout the spectrum of the AYA ages (ie, diagnosed up to age 29 years). If the AYA agenda became a national priority, then resources could be made available for the other provinces to join in this endeavor and develop a national cohort of AYA survivors that could be followed longitudinally. Nested case-control or case-cohort studies from this national cohort would provide unique opportunities to further study cardiopulmonary morbidity and other major health problems that lead to substantial loss of life and productivity. The economic impact of interventions aimed at increasing the rates of risk-based survivorship health care4, 32, 33 could be assessed and resources could provided based on better evidence.


Funding for the National Task Force on Adolescents and Young Adults with Cancer has been made possible by a financial contribution from Health Canada through the Canadian Partnership Against Cancer. Funding for the workshop was provided by C17; the Advisory Board of the Institute for Cancer Research at the Canadian Institutes for Health Research (CIHR); the Public Health Agency of Canada; the Ontario Institute for Cancer Research; the Meetings, Planning and Dissemination Grants program of the CIHR; the Terry Fox Research Institute; LIVESTRONG, formerly the Lance Armstrong Foundation; the Canadian Cancer Society Research Institute; Young Adult Cancer Canada; Hope and Cope; and the Comprehensive Cancer Centre at the Hospital for Sick Children, Toronto, in addition to the support provided by the Canadian Partnership Against Cancer to the Task Force on Adolescents and Young Adults with Cancer.


The authors made no disclosures.