Illustration by Eva Vázquez
Several recent studies examining the global burden of cancer on adolescents and young adults (AYAs) show the growing magnitude of the disease’s impact on the lives of individuals between the ages of 15 and 39. Although considered a rare occurrence, cancer in this age group has risen by nearly 30% over the past 4 decades in the United States,1 reaching nearly 90,000 new cases each year, and causing the deaths of more than 9,000 adolescents and young adults.2
According to research by Nickhill Bhakta, MD, MPH, Assistant Member of St. Jude’s Faculty at St. Jude Children’s Research Hospital and Director, Sub-Saharan Africa Region, St. Jude Global, as well as 730 collaborating scholars, globally, there are about 2 million incidents of cancer in AYAs and 396,000 deaths each year,3 but actual figures are likely much higher, said Dr. Bhakta. The reasons for the difference are because cancer registries in many low-resource countries are incomplete or nonexistent, the cause of death may not always be captured in death certificates, or the information recorded may be inaccurate.
“When you compare the global incidents and mortality rates for AYAs diagnosed with cancer, there is a disconnect. There is incomplete data registration in cancer registries, particularly in low- and middle-income countries. For example, mortality statistics often come from totally separate registries, including vital statistics registries, which may not be linked to the cancer registry. Moreover, even though a patient dies of cancer, it may not be recorded in the death certificate, meaning no registry captures the data,” said Dr. Bhakta. “I think nearly 400,000 deaths from cancer worldwide in adolescents and young adults is the floor and not the ceiling.”
Because the incidence and mortality rates do not tell the full story of the impact of cancer on this population, Dr. Bhakta and his colleagues analyzed data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 to assess the outcome of disability-adjusted life-years experienced by AYAs.4 Disability-adjusted life-years are a key measure of disease burden that includes both fatal and nonfatal impacts of disease and are used in the development of national and global health policy, said Dr. Bhakta. According to the researchers’ analysis, cancer was the fourth leading cause of death—behind accidents, homicide, and suicide—and the tenth leading cause of disability-adjusted life-years in adolescents and young adults globally, 23.5 million among 22 causes of disability-adjusted life-years at this level in the GBD hierarchy3 (one disability-adjusted life-year is the equivalent of 1 year of healthy life lost). The greatest concentrations of disability-adjusted life-year srates are in parts of Asia, southern sub-Saharan Africa, and South America.
Again, although these findings highlight that cancer is a major contributor to death and disease burden, even when compared with high-profile communicable diseases such as HIV/AIDS and sexually transmitted diseases, they are likely a low estimate of the true dimension of disease hardship on this patient population.
“I think nearly 400,000 deaths from cancer worldwide in adolescents and young adults is the floor and not the ceiling.”— Nickhill Bhakta, MD, MPH
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“Our analysis showing that AYA cancer had the tenth highest disability-adjusted life-years burden globally is probably an underestimate, because it does not account for the long-term side effects of treatment some survivors may have, including cardiotoxicity or secondary cancers, or the cost of cancer care for assessing the lifelong disease burden of cancer in this population, such as financial hardship,” said Dr. Bhakta. “This is an area where we need to do better if we are going to continue to emphasize the full consequences of cancer to policymakers and improve the allocation of resources for AYAs with cancer.”
Measuring the Burden of Cancer on AYAs
Predictably, the majority, 91.4%, of the worldwide AYA cancer disability-adjusted life-years burden and highest number of deaths are concentrated in low- and middle-income countries, where access to cancer care is limited, and the highest incidence rates were seen in high-income countries. The four cancer types that were the greatest contributors to the globally disability-adjusted life-years burden were breast cancer (10.6%); brain and central nervous system cancers (7.4%); colon and rectal cancers (7%); and stomach cancer (6.7%). However, when counted as a single cancer group rather than as individual subtypes, leukemia is the largest contributor to the global cancer disability-adjusted life-years burden (12%).3
Findings from an earlier study by Gupta et al investigating the incidence of cancer among AYAs in 41 countries, from 1998 to 2012, showed there were statistically significant increases in 23 countries of thyroid and testicular cancers and several obesity-linked malignancies (eg, colorectal, breast, kidney, esophageal, pancreas, and multiple myeloma), especially in the United States, United Kingdom, Canada, Japan, South Korea, Australia, and the Netherlands.5 And although the incidence rates for cervical cancer in several countries, including India and in some countries in Europe and the Americas, decreased, increases were observed in Belarus, China, Turkey, and the United Kingdom.
Decreases in lung cancer were observed in men in China, Spain, Turkey, and the United States, but increases in women were seen in Australia and Japan. Notably, the incidence rates for melanoma were reduced by more than 2% per year in several countries, including Australia and the United States, but they increased in many European countries.5
“We are only just now beginning to understand the entire burden of cancer in AYAs.”— Miranda M. Fidler-Benaoudia, PhD
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“While cancer in this age group is rare, what our paper showed is that we are seeing increases around the world, and that although these numbers are low, they are growing,” said Miranda M. Fidler-Benaoudia, PhD, Research Scientist, Department of Cancer Epidemiology and Prevention Research; Adjunct Assistant Professor, Oncology and Community Health Sciences at the University of Calgary, Arnie Charbonneau Cancer Institute; and principal investigator of this study. “We know that obesity is increasing around the world, even at young ages. Given that many of the cancers we found have a link to excess body weight, it seems that obesity may be causing an increase in cancers in younger individuals. However, there could be other mechanisms at fault besides obesity, such as physical inactivity, poor nutrition, and the microbiome, or even another risk factor that is linked to the same pathway.”
Understanding the Uniqueness of Cancer in Young Adults
Although the 5-year relative survival rate has improved for AYAs in the United States over the past 40 years, increasing from about 70% to approximately 85%, it still lags behind improvements seen for younger and older adult survivors. In children, the 5-year relative survival rate has risen from about 60% to about 85%, and in older adults, it rose from about 50% to about 70%.6
Worldwide, the mortality rate of AYAs with cancer significantly decreased from 1990 to 2019, with an estimated annual percentage change of 0.38 (95% confidence interval = 0.36–0.39) and –0.93 (95% confidence interval = -0.95 to -0.92), respectively.7
In addition to worse survival outcomes, a cancer diagnosis in this population comes at a time of developmental transition in their lives; it can affect their physical development, mental health, quality of life, educational and vocational achievements, and the shift to independence and autonomy. In addition, the challenges AYAs experience as the result of their cancer diagnosis may be lifelong.
Studies have showed that compared with young people who have no cancer history, AYA cancer survivors undergo a higher prevalence of chronic disease, disability, and poorer physical health over their lifetime.8 In the United States, these young cancer survivors also experience substantially higher rates of adverse mental health outcomes, including a 30% higher rate of outpatient mental health visits and a 20% increased risk of a severe psychiatric episode, compared with their counterparts without a history of cancer. Furthermore, younger cancer survivors treated in adult cancer centers experience substantially higher (80%) outpatient mental health visits compared with those treated in pediatric cancer settings.9
In low- and middle-income countries, where a cancer diagnosis often results in an additional burden of shame and stigma, access to psychological care is poor or nonexistent.
“There is still not enough emphasis on psychosocial care during cancer therapy in the majority of centers in low- and middle-income countries, simply because of the financial limitations as well as the expertise that is needed to treat the psychosocial consequences of a cancer diagnosis,” said
“A central role of oncologists—everywhere—is to identify the need for mental health services and direct the patient for care accordingly.”— Raya Saab, MD
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Raya Saab, MD, Associate Professor in the Department of Pediatrics, Division of Hematology-Oncology at the American University of Beirut. “There is an increasing realization and understanding of the need to provide psychosocial care. Over the past few years, many centers even in lower middle-income countries have focused on trying to make that care available, but financial barriers and reimbursement issues continue. As a result, patients’ access to psychosocial support is still relatively limited. A central role of oncologists—everywhere—is to identify the need for mental health services and direct the patient for care accordingly.”
Calculating the Lifelong Burden of Cancer
In the United States, young adult cancer survivors are also more likely to be uninsured or underinsured; they are also more likely to skip care because of out-of-pocket costs—current estimates suggest that, on average, young adults spend an extra $3,170 per year in medical expenses than nonsurvivors10—go into debt, and file bankruptcy after a cancer diagnosis than their older adult counterparts.11
“When I try to explain why cancer affects AYAs differently than children or older adults, I explain it in terms of grief and loss,” said Karen H. Albritton, MD, Medical Director of the Adolescent and Young Adult Program, Hematology and Oncology Center at Cook Children’s Medical Center, Fort Worth, Texas. “At this time in their lives, AYAs are future oriented. Even if they don’t have an exact plan in mind, they have a sense of what is supposed to happen to them along life’s trajectory; then when cancer hits, their loss is twofold. They experience immediate losses: loss of their hair, loss of their social and educational lives, and possibly loss of their job. And then there are the losses of their imagined future, including loss of fertility and financial security. It is a very different burden of grief and loss than is experienced by older adults with cancer.”
“It is a very different burden of grief and loss [for AYAs] than is experienced by older adults with cancer.”— Karen H. Albritton, MD
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Dr. Fidler-Benaoudia agreed. “Adolescents and young adults are in that middle group that has not received a lot of research attention. There is greater advocacy for childhood cancers and for cancers diagnosed in older adults, who have the highest incidences of the disease. We are only just now beginning to understand the entire burden of cancer in AYAs.”
Improving Long-Term Survival
To gain knowledge and address the issues unique to adolescents and young adults with cancer as well as to improve their long-term survivorship, in 2015, the European Society for Medical Oncology and the European Society for Pediatric Oncology established the Cancer in AYA Working Group. According to the findings from the Working Group, the two most important medical challenges facing AYAs with cancer are the existence of and/or access to specialized centers or service networks, and the development of clinical trials investigating novel therapeutics to improve outcomes, which is hindered by historically low enrollment of AYA patients in research studies. For example, from 2004 to 2013, of 23,328 total enrollments in Southwest Oncology Group (SWOG) trials, just 2,380 (10.2%) were adolescents and young adults.12
Barriers to participation in clinical trials include the following: a paucity of trials for common AYA cancer types; the place of care (community sites enroll a lower proportion of AYAs in clinical trials than trials offered in academic settings12); the restrictive age eligibility criteria, with the lower age limit of 18 years making “young” AYAs ineligible for many industry-led clinical studies; trial designs that do not accommodate AYAs’ specific lifestyle, education, and employment requirements; and lack of awareness of available trials by treating oncologists.13 Lack of understanding of the tumor biology that distinguishes cancers in this population compared with younger and older patients with cancer also contributes to few advances in treatment and only modest gains in outcomes.
“Many cancers diagnosed in AYAs are sarcomas, but even the various subtypes of sarcomas have a distinctive biology and diagnostic features and likely need to be addressed differently in terms of therapy,” said Dr. Saab. “Several groups are currently focusing on better understanding the molecular underpinnings of AYA cancers and to specifically categorize the tumors molecularly. However, you need more collaboration internationally to succeed due to the relatively small number of AYA cases compared with older adults with the disease. Addressing the barriers to care and the relatively low rate of enrollment into clinical trials will also be essential to make sure we are capturing the data for these patients and identifying how best to bridge the gaps in care.”
Closing the Gaps in Care
Closing the gaps in care for AYAs with cancer will also entail the integration of AYA cancers into overall cancer control planning and universal health coverage, according to Dr. Bhakta. “Cancer control planning has always focused on adults with cancer, and it has mostly been focused on critical diseases such as breast, colorectal, and cervical cancers,” he said. “But there isn’t a holistic approach to cancer control strategies. Since AYAs are a unique patient population with unique needs at a cancer control level, this is an important paradigm that needs shifting. We are starting to get there with childhood cancers, but AYAs have not yet entered the conversation in an important way.”
Complicating initiation of these conversation, according to Dr. Bhakta, is the lack of a clear understanding of the full sense of disease burden on this patient population and how it differs from younger and older adult survivors.
“At the end of the day, publication of our study and others are just pieces of paper. The question is, how do we translate our findings into meaningful action?” Dr. Bhakta said. “The reason we advocated so strongly to launch our study is because of the opportunity to look at AYA cancer care as a more holistic health-system issue and where AYA cancers fit within the prioritization of governments.”
Development of contextually relevant guidelines for treating and monitoring AYAs with cancer and formation of an operational national cancer control policy, strategy or action plan, and cancer registries within each country will provide governments with the tools to assess the burden of cancer in their AYA populations and allocate appropriate resources for their care and to measure the performance of specific interventions, according to Dr. Bhakta.
“Our study provides the data on AYA patients governments and advocates can use, both in low- and high-resource settings, to help inform their policymaking decisions on how to improve cancer care and cancer research for this unique population,” concluded Dr. Bhakta. “We hope to build on our findings, but this gives us an important first step in better addressing the needs of AYAs with cancer throughout survivorship.”
DISCLOSURE: Dr. Bhakta, Dr. Fidler-Benaoudia, Dr. Saab, and Dr. Albritton reported no conflicts of interest.
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