Adolescents and young adults with cancer require dedicated services, research
Going through cancer during transitional adolescent and young adult years can present additional social, financial and mental health challenges that add to the stressors of diagnosis and treatment.
Cancer cases among adolescents and young adults (AYAs) — defined as those diagnosed between ages 15 to 39 years — have risen by 29.6% over the last 4 decades, according to a study published in December in JAMA Network Open. Other research shows AYAs with cancer frequently experience disparities in outcomes and long-term mental health effects.
Although greater effort has been made to distinguish AYAs from pediatric and older adult cancer populations, this group remains under-researched compared with other age groups, presenting challenges to the clinicians who treat them.
Programs dedicated to research and clinical care for AYAs with cancer have become more prominent across the country in the last decade; however, no clear infrastructure exists to help the results of AYA research reach AYA patients themselves.
This means that many AYAs aren’t benefiting from progress made over the last 20 years, according to Sumit Gupta, MD, PhD, staff oncologist and clinician investigator at The Hospital for Sick Children in Toronto.
“For example, we know that a pediatric-based treatment protocol are near definitively proven to be 15% to 20% better in terms of survival than an adult-based protocol for AYAs with acute lymphoblastic leukemia,” Gupta told HemOnc Today. “Study after study continues to show, particularly in the U.S., that a lot of AYAs are still not being treated with pediatric-based protocols, , either because their practitioners aren’t familiar with these results or because they’re not going to centers that have that knowledge, which is extremely concerning.
“Whether it’s a protocol that improves survival, whether it’s the knowledge that long-term mental health is a major issue — how do we actually disseminate that information?” he added.
HemOnc Today spoke with hematologists and oncologists who care for AYAs about disparities in outcomes among the population, the importance of addressing the unique psychosocial issues AYAs face, and the need to prioritize clinical trials and research networks for this group.
Room for improvement
The field of AYA cancer care first became a possibility when, in 1996, Archie Bleyer, MD, released his seminal research showingthat adolescents aged 15 to 19 years did not benefit from the same cancer therapy as children. Ten years later, NCI and the Livestrong Foundation collaborated to launch the AYA Oncology Progress Review Group, which developed recommendations to advance AYA oncology.
In its current state, the AYA field is still in fledgling stages.
“When I said the term ‘AYA’ to medical oncologists 5 to 10 years ago, they often wouldn’t know what that was. Now, most do,” Rebecca H. Johnson, MD, pediatric hematology-oncology specialist, at Mary Bridge Hospital, MultiCare Health System in Tacoma, Washington, told HemOnc Today. “It’s a very positive change that people are aware of AYAs as a distinct group that may require extra resources from the medical team.”
That positive change is crucial to help meet the needs of more AYAs, as data published in JAMA Network Open show cancer incidence is increasing among this age group.
Scott and colleagues used SEER data to evaluate 497,452 AYAs (59.1% female, 79.9% white) diagnosed with cancer between 1973 to 2015.
They found the cancer rate in this group increased by 29.6% over that time, with a mean annual percentage change per 100,000 persons of 0.53 (95% CI, 0.42-0.64; P < .001). This translated to an increase from 57.2 invasive cancer diagnoses per 100,000 AYAs per year to 74.2 per 100,000 AYAs.
In addition to rising diagnoses, poor long-term survival among AYA patients is another worrisome trend.
OS rates of AYA cancer survivors appeared lower than the age-adjusted expected survival rates of the general population, according to a study published last year in Cancer.
Additionally, researchers found that although short-term OS rates improved over time, long-term OS rates did not improve at the same rate.
“We need to fill in the gaps and find out what’s causing these patients to not live as long as their peers, what’s causing them to develop chronic illnesses, what these chronic illnesses that they’re developing are, and what their quality of life is like,” Michael E. Roth, MD, associate professor of pediatrics and co-director of the AYA program at The University of Texas MD Anderson Cancer Center, who served as a researcher on that study, told HemOnc Today.
In addition to being at a critical life stage — during which they may be starting college, a career a relationship or a family — AYAs also could have at least another “half-century-plus” of life, Roth said.
“We owe it to them as oncology providers to think about their whole life, and to make sure we are supporting them throughout their journey and not just through their initial diagnosis,” he said.
Any progress in improving AYA care has not been shared across the population. Many of the disparities in outcomes observed across the entire spectrum of cancer care also are apparent among the AYA population.
Because prior research demonstrated that AYAs did not have the same improvement in survival as children and older adults, Moke and colleagues evaluated 1988 to 2014 data from the California Cancer Registry to evaluate whether more recent treatment advances had leveled those differences.
Results, published in 2019 in JNCI Cancer Spectrum, did show survival improvement, but alongside growing disparities in subgroups, including among those with advanced-stage disease, racial and ethnic minorities, and patients of low socioeconomic status (SES).
Specifically, risk for death appeared significantly higher for Black patients (site-specific adjusted HR [aHR] = 1.46, 95% CI, 1.42-1.5), Asian and Pacific Islander patients (aHR = 1.12, 95% CI, 1.09-1.15), and Latino patients (aHR = 1.06, 95% CI, 1.04-1.08) compared with “non-Latino” whites, and for patients of low vs. high SES (aHR = 1.31, 95% CI, 1.29-1.34).
Ensuring more equal treatment “comes to broader societal questions also relevant to AYAs without cancer,” Gupta said. “I think it’s pretty well-recognized that AYAs are a vulnerable group and there are these AYA disparities,” he said, citing another study by Smith and colleagues, published in 2012 in Cancer, that evaluated AYAs with Hodgkin lymphoma.
“That study found that if you were uninsured, you were way more likely to present with advanced-stage Hodgkin lymphoma than limited-stage disease,” he said. “These disparities clearly exist within an already disadvantaged population.
“There are unique challenges in the U.S. with insurance, funding and access, but the overall challenges occur here in Canada, as well,” Gupta added. “I frankly don’t have great answers for how to ensure these inequities don’t continue. It’s going to take prioritization on the part of decision makers and policymakers.”
In another study, published in January in Journal of the National Cancer Institute, Murphy and colleagues found similar disparities among AYAs with cancer, which they characterized in individual cancer types as “striking.”
Researchers used population-based 1995 to 2016 data from the Texas Cancer Registry to estimate 5-year relative survival of common AYA cancers among 88,000 patients, examining disparities in survival by race and ethnicity, neighborhood poverty, urban vs. rural residence and insurance type.
Among their findings, researchers found 5-year survival rates for non-Hodgkin lymphoma of 74.5% for white patients compared with 57% for Black patients and for ALL of 66.5% for white patients vs. 44.4% for Hispanic patients. Such disparities existed even for good-prognosis cancers like testicular cancer, for which researchers observed 5-year survival rates of 96.6% for white patients vs. 88.7% for Black patients.
Another concerning takeaway: survival rates among the AYAs studied decreased as poverty increased.
“Now that we understand there is a problem, we need to identify how to make sure that these patients have higher cure rates,” Roth, one of the researchers on the study, told HemOnc Today. “How do we make sure that their survival is not adversely affected just by being born into a family that doesn’t have the same means as another family? It’s a critical issue and it’s incredibly important to make sure all our patients get the same care, have the same treatment and have the same outcomes.”
Some of the factors contributing to disparities, such as delays in diagnosis, poor access and/or adherence to care, and availability of treatment, may be the result of “structural racism,” according to the researchers. They cited the example of Black patients with hematologic malignancies who are less likely to receive allogeneic hematopoietic stem cell transplantation due to underrepresentation in national marrow donor registries.
“We’re in a time now where the question needs to be, ‘What do we do about it?’” Roth said. “That’s a major goal right now within the AYA research community. We have the evidence needed to launch interventions — so how do we do better?”
Doing better begins with prioritization through dedicated programs and making sure clinical trials are available nationally to all AYA populations, Roth said.
Twenty-five years ago, while she was a second-year internal medicine/pediatrics resident at Penn State, Johnson was diagnosed with breast cancer. She was in her 20s and completely healthy beforehand, with no family history of cancer.
“It was completely shocking and so scary,” she said. “I knew enough about medicine to read the literature and doctors [who taught me in my residency] were straight with me. They told me breast cancer is rare in young women, that young women don’t do as well as older women, and that they didn’t know why. I said, ‘Nobody knows why?’ And they said, ‘No.’ I found it quite amazing that no one had ever systematically investigated that question.”
Years later, when Johnson moved across the country to launch her career, Bleyer became her mentor, and he helped her conduct a research analysis that showed breast cancer is not that uncommon for young adults.
“A woman’s chances of getting breast cancer by the time she is 40 years are actually one in 190,” she said.
Since the time of Johnson’s cancer diagnosis, progress has been made in AYA research and knowledge among dedicated teams.
“There’s a big push now to make sure there are AYA champions at every institution. There need to be folks embedded in institutions leading the way, making sure patients’ health and overall care are optimized,” said Roth, who added the MD Anderson AYA Program treats more than 1,000 AYAs a year.
“We’re not there yet; we still have a lot of work to do,” he said. “But we’re at a good point where people are recognizing the importance and benefits of these programs.”
Advances can be facilitated further by increasing the presence of and access to clinical trials for AYAs.
“Progress is made through clinical trials,” Johnson said. “Survival improvements happen directly as a result of clinical trials being offered for patients ... there’s a direct correlation.”
In a study published last year in Journal of Adolescent and Young Adult Oncology, Roth and colleagues formed what they called a Responsible Investigator Network to uncover site-level issues that could result in poor AYA enrollment in clinical trials. The research included 145 responsible investigators representing 122 demographically and geographically diverse sites.
They concluded that four major barriers existed: lack of available trials; poor communication between pediatric and medical oncology; logistical constraints to accessing trials; and lack of leadership support, sufficient resources and appropriate policies.
“Often when clinical trials are available at the national level, many sites are not opening them within their institution,” Roth said. “One of the explanations potentially is that AYA cancers are all rare cancers. Approximately 90,000 AYAs will be diagnosed each year with cancer, but that’s all diagnoses.
“So, when you open an AYA trial, you’re not likely to enroll a large number of patients on that study at your site,” he added. “But, it’s essential that we contribute to the mission and ensure that we are making these trials available to our AYAs. Otherwise, we will never know what the optimal treatment approaches and therapies are for these patients.”
Research funding — whether from government entities, philanthropic efforts or both — also can help fuel those clinical trial efforts.
“In the 1970s there was a push to cure pediatric cancers, resulting in government funding to support many clinical trials,” Johnson said. “The same thing occurred with breast, prostate and lung cancers in the ’80s — lots of government funding, lots of trials and, ultimately, better survival.”
A lasting psychological effect
Whether on the younger end of the age group and just beginning college or a career, or on the older end of the population and perhaps starting a family, AYAs are a unique population that meets cancer at a particularly critical time in life.
Faced with a premature confrontation with the possibility of death, AYAs may have more dramatic psychosocial sequelae from their cancer diagnosis than these other groups.
“I think it’s fair to say that the opportunity for a lasting effect is heightened purely as a function of the age at which they’re diagnosed,” Stacy D. Sanford, PhD, clinical health psychologist at Robert H. Lurie Comprehensive Cancer Center of Northwestern University, director of the cancer center’s AYA Cancer Program, and associate professor in the department of psychiatry and behavioral sciences, told HemOnc Today.
According to a study published in 2017 in Cancer, AYA survivors appeared more at risk for mental distress than a healthy comparison group, but they infrequently talked to a mental health care professional.
Kaul and colleagues used the 2013 and 2014 National Health Interview Surveys to identify 875 AYA cancer survivors at least 5 years from their initial diagnosis. Compared with a healthy control group, these AYA survivors more frequently reported both moderate (23.2% vs. 16.9%) and severe (8.4% vs. 3%; P < .001 for both) mental distress.
Additionally, 74.7% of AYA survivors who reported moderate mental distress and 52.2% with severe mental distress said they had not talked to a mental health professional.
Sanford said she often meets AYA patients for the first time after they’ve completed their cancer treatment and are wondering how to put their lives back together.
“Ideally, patients should be screened for distress regularly as a hallmark of patient-centered care,” Sanford said, referring to National Comprehensive Cancer Network guidelines. “Not everyone will need those types of services. But, at a minimum, we should be screening for it. Sadly, not everyone will have easy access to a mental health provider, which again raises this issue of disparities.”
Sanford and Jennifer L. Reichek, MD, MSW, launched Northwestern’s comprehensive AYA program in 2009, offering resources and services aligned with nationally established guidelines and standards of care. It includes a staff with psychologists, social workers, dieticians, an AYA-specific navigator, a fertility preservation expert, a patient advocacy group of AYA cancer survivors, and more.
AYA patients in their care undergo a biopsychosocial assessment upon arrival.
“We know that people with strong support systems, regardless of their age, have better outcomes,” Sanford said. “That’s why biopsychosocial assessment at the point of diagnosis is so crucial and it’s why we ask, ‘Who is your support system?’ and, ‘Who is your primary caregiver?’ If they don’t have anybody, then we know that person is going to need more support and we’re going to have to keep our eyes on them.”
When mental health is neglected in long-term follow-up, the results can be troubling, as suggested by a study published in February in Journal of Clinical Oncology. De and colleagues found AYA survivors are at substantially greater risk for adverse mental health outcomes.
The research team, led by Gupta, used a population-based database of all AYAs aged 15 to 21 years in Ontario, Canada, who were diagnosed with one of six common cancers from 1992 to 2012 (n = 2,208), who they compared with a matched healthy cohort (n = 10,457). They defined two primary mental health outcomes: a low-severity visit (any outpatient visit for a mental health complaint to a family physician or psychiatrist) and a severe psychiatric episode (any mental health-related ED visit, hospitalization or suicide).
The results showed 5-year survivors experienced higher rates of outpatient mental health visits compared with the matched controls (671 visits vs. 506 visits per 1,000 person-years; adjusted RR = 1.3; 95% CI, 1.1-1.5). Also, risk for a psychotic disorder-associated severe event appeared doubled among survivors (HR = 2; 95% CI, 1.3-2.4), although absolute risk remained low (15-year cumulative incidence = 1.7%; 95% CI, 1-2.7).
The researchers recommended long-term mental health surveillance but, Gupta said, a more effective short-term intervention is simply informing patients and providers about mental health effects.
“Even just knowledge on the part of patients that this is a known side effect [is helpful],” Gupta said. “I tell my patients, if the chemotherapy gave you long-term heart weakness, we’d think nothing of involving a cardiologist. This should be no different. The evidence shows that this is a potential side effect of going through the cancer experience. Just as we wouldn’t hesitate before getting that cardiologist involved, we shouldn’t hesitate in getting some sort of mental health support or care involved, as well.”
‘Keep moving forward’
As an AYA survivor-turned-director of an AYA program, Johnson comes at AYA cancer research from a unique perspective.
“Little kids don’t have major existential crises with cancer diagnoses; it’s not developmentally appropriate,” Johnson said. “Older adults have some expectation that they might potentially get sick. They undergo cancer surveillance, and they have friends who have had cancer and may have had other medical issues themselves. In contrast, a cancer diagnosis for previously healthy teens and young adults is like a stroke of lightning coming out of nowhere.
“In our society, many AYAs have never had any major encounters with the medical system, and they and all of their friends may have no experience with serious illness,” she added. “So, AYAs may have limited health literacy, and their peer group may not understand what they’re going through.”
This is where AYA-specific care, tailored to this unique population, is critical, experts said. Whether it’s through an AYA program such as those at MD Anderson or Northwestern, among many others, or a specialized charity such as Teenage Cancer Trust in the U.K., treatment from providers trained in AYA care is essential.
“We’re getting there,” Gupta said, adding that comprehensive, structured AYA programs are becoming more commonplace.
“What we lack in Canada and the U.S. are systemwide-type interventions or cancer care systems for AYAs, whether physical space, teams or some combination,” he added. “That’s where a lot of other countries have gone, but we haven’t gotten there in the U.S. or Canada yet.”
Gupta sees the out-of-place feeling his older “250-pound hockey player” teens have when they’re being treated in a room at The Hospital for Sick Children and there are pictures of “Paw Patrol” on the walls.
Johnson remembers almost never seeing AYAs her own age when undergoing chemotherapy.
“Throughout my whole cancer treatment, I met only two people around my age,” she said. “Those few friendships changed my whole life, and they helped me to move forward.”
Experts with whom HemOnc Today spoke agreed that prioritizing the AYA population means providing more care specific to their unique needs, more funding for trials in this group, and more knowledge and awareness of treatments that exist and progress that has been made.
Despite the progress over the last 2 decades, there are still unexplored avenues toward providing more optimal treatment, delivering better care, and improving both OS rates and quality of life of AYA survivors.
“[We need to] keep moving forward and try to advance the science, not only on the medical and biology sides, but also on the psychosocial side,” Sanford said. “We need to advocate for young adults and get to a place where our institutions are more readily recognizing and supporting the work that needs to be done to address this patient population’s needs instead of treating them like they are a 60-year-old with cancer.”
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For more information:
Sumit Gupta, MD, PhD, can be reached at The Hospital for Sick Children, 555 University Ave.,, Toronto, ON M5G 1X8, Canada; email: firstname.lastname@example.org.
Rebecca H. Johnson, MD, can be reached at Mary Bridge Children’s Hospital, MultiCare Health System, Department of Pediatrics, PO Box 5299, 311 S. L St., Tacoma, WA 98405; email: email@example.com.
Michael E. Roth, MD, can be reached at Department of Pediatrics, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX, 77030; email: firstname.lastname@example.org.
Stacy D. Sanford, PhD, can be reached at Northwestern University Feinberg School of Medicine and Robert H. Lurie Comprehensive Cancer Center of Northwestern University, 675 N. St. Clair St., Suite 21-100, Chicago, IL, 60611; email: email@example.com.