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Understanding the Uniqueness of Cancer and Survival in Adolescents and Young Adults

A Conversation With Kimberly D. Miller, MPH


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Numerous studies over the past 4 decades have chronicled the lack of progress in improved outcomes for adolescents and young adults (AYAs)—defined by the National Cancer Institute as those ranging in age from 15 to 39—diagnosed with cancer compared with children and older adults diagnosed with the disease. According to data from the Surveillance, Epidemiology, and End Results registry, although 5-year relative survival has improved for AYAs over the past 40 years, increasing from about 70% to approximately 85% (a 15% increase), it still lags behind improvements seen for younger and older adult survivors. In children, 5-year relative survival has risen from about 60% to about 85% (a 25% increase), and in older adults, it rose from about 50% to about 70% (a 20% increase).1

The reasons for the discrepancy in AYA survival outcomes are many, including the unique genetic and biologic features of AYA malignancies, lack of standardized therapeutic approaches, poor therapy compliance, lack of access to health insurance and health care, and race and ethnicity, according to a recent study by the American Cancer Society (ACS).2 The study analyzed population-based cancer incidence and mortality for AYAs by age group: 15 to 19 years, 20 to 29 years, and 30 to 39 years.

Kimberly D. Miller, MPH

Kimberly D. Miller, MPH

Although 5-year relative survival in AYAs was similar across all age groups for all cancers combined (between 83% and 86%), it varied widely for some cancers, including acute lymphocytic leukemia (ALL), 74% in the 15- to 19-year-old group vs 51% in those aged 30 to 39; and brain tumors, 77% vs 66%, respectively. These findings reflect differences in histologic subtype distribution and treatment, said Kimberly D. Miller, MPH, an epidemiologist in Cancer Surveillance at the American Cancer Society and the lead author of the study.

“We have known the survival trends in AYAs for many years, but what surprised me about our study’s results is the huge disparity in the 5-year relative survival for ALL and brain cancer between the 15- to 19-year-old and 30- to 39-year-old groups,” Dr. Miller said. “This finding highlights an opportunity for further research and the need for additional progress in reducing the cancer burden in AYAs, among all age groups.”

The study also highlights patterns in worse cancer mortality among AYA racial/ethnic minority patients that are eerily similar to those seen in their older adult counterparts. According to the study’s findings, the 5-year survival in AYAs for all cancer types combined is lower in racial/ethnic minority patients, especially for non-Hispanic Black AYAs compared with non-Hispanic White AYAs—75% vs 88%, respectively. The largest 5-year cancer-specific survival disparities occurred among those who are non-Hispanic Black or Hispanic compared with non-Hispanic White AYAs—for ALL, 57% and 58% vs 71%, respectively; and for female breast cancer, 78% and 85% vs 89%—and among Native Americans/Alaska Natives compared with non-Hispanic Whites for colorectal cancer, 59% vs 72%.

“It is really striking to look at the large racial/ethnic disparities in cancer in AYAs because this is a huge point that often gets missed,” said Ms. Miller.

Equally disturbing is the overall increase in cancer incidence among all AYA age groups over the past decade, largely the result of increases in thyroid cancer, which rose by approximately 3% annually among those aged 20 to 39 and by 4% among those aged 15 to 19, according to the ACS study. Cancer incidence also increased in most age groups for several cancers linked to obesity, including kidney cancer, 3% annually across all age groups; uterine corpus cancer, 3% in AYAs aged 20 to 39; and colorectal cancer, 0.9% to 1.5% in the same age group.

Guest Editor

Brandon Hayes-Lattin, MD, FACP

Brandon Hayes-Lattin, MD, FACP

Adolescent and Young Adult Oncology explores the unique physical, psychosocial, social, emotional, sexual, and financial challenges adolescents and young adults with cancer face. The column is guest edited by Brandon Hayes-Lattin, MD, FACP, Professor of Medicine and Medical Director of the Adolescent and Young Adult Oncology Program at the Knight Cancer Institute at Oregon Health and Science University in Portland.

Conversely, rates declined dramatically for melanoma in AYAs aged 15 to 29, 4% to 6% annually, but remained stable among those aged 30 to 39. The study also found that overall cancer mortality declined from 2008 to 2017 by 1% annually across all age and gender groups, except for women aged 30 to 39, among whom rates were stable due to flattening declines in female breast cancer. However, mortality rates increased for colorectal and uterine cancers in those aged 30 to 39.

According to the ACS, approximately 89,500 AYAs will be diagnosed with cancer this year, and 9,270 will die of the disease.2 The ASCO Post talked with Ms. Miller about the findings from this study and how to improve oncology care and survivorship for AYAs with cancer.

Access to Tanning Devices and Melanoma Incidence

Do you have insight as to why melanoma rates are declining in younger AYAs?

I would say that regulations in some states restricting minors’ use of tanning devices, including tanning beds, is having an impact on melanoma occurrence in younger people. Changes in sun protection behavior in this age group could also be a factor.

Why melanoma incidence has not changed in young adults in their 30s is more complicated to discern. We did see a slight decline in men, but not women. This could be an area for future investigation.

Underlying Mechanisms in Young-Onset Colorectal Cancer

Is there new information on the underlying biologic mechanisms that might explain the uptick in young-onset colorectal cancer incidence?

There is increasing evidence indicating that colorectal cancer in AYAs is molecularly distinct from that in older patients, and this is a rapidly evolving area of research. We are trying to understand why we are seeing increases in colorectal cancer in younger adults, whereas the rates for older adults have decreased.

There is growing interest in determining the roles that obesity, diet, lifestyle, family history, and epigenetics may be playing in the development of early-onset colorectal cancer. The study of epigenetics is going to be integral to understanding what is enhancing the susceptibility to colorectal cancer in young adults, so we can devise better prevention and treatment strategies for this younger population.

“The study of epigenetics is going to be integral to understanding what is enhancing the susceptibility to colorectal cancer in young adults.”
— Kimberly D. Miller, MPH

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Understanding the Racial Disparities in Breast Cancer Incidence

Another disturbing trend from your report is that incidence rates for breast cancer in non-Hispanic Black AYAs is 14% higher than it is for non-Hispanic White AYAs. Do you know why there is such a racial disparity in breast cancer incidence?

The elevated breast cancer rate in non-Hispanic Black women is almost entirely driven by hormone receptor–negative disease, especially triple-negative breast cancer. Why triple-negative breast cancer rates are higher in Black women compared with other races and ethnicities is not well understood, but it is definitely an area that needs more research.

Notably, the Black-White disparity in breast cancer mortality is largest in the AYA age group, with death rates nearly double for Black AYA women (3.9 vs 2.0 for White AYA women, per 100,000 population) and declines with age.3 The disparity in part reflects the higher rates of aggressive tumors with a poorer prognosis in Black women, but lower survival rates are also attributable to inequities in access to high-quality cancer care.

Filling the Research Gaps

Achieving equitable access to health care is among the conclusions from your report that could help reduce cancer incidence and cancer-related death among AYAs. What are some other factors limiting progress in these areas among adolescents and young adults?

We need to fill the research gaps in the etiology and basic biology of cancer in this population, as well as in more effective treatment and survivorship strategies. We have to improve AYA clinical trial participation, not only to better understand the heterogeneity of cancer in this age group, but also to determine treatment guidance specifically tailored for these patients. These survivors also experience greater financial hardship than older cancer survivors, have higher uninsured and bankruptcy rates, and more frequently forgo needed medical care because of cost.

There isn’t a lot of public discussion about ­cancer occurrence in this patient population, and, in addition to a much greater research focus on better treatment protocols, more attention needs to be paid to how to improve survivors’ lives after cancer. For example, a separate study recently found that a substantial proportion of AYA patients with cancer, especially females (38%, compared with 18% of males), who did not make fertility arrangements prior to cancer treatment failed to do so because they were not adequately informed of their options.4 We need to raise ­public and clinical awareness of cancer occurrence in adolescents and young adults, so patients and clinicians become alert to the early symptoms and signs of cancer and more young lives can be saved. 

DISCLOSURE: Ms. Miller reported no conflicts of interest.

REFERENCES

1. Coccia PF: Overview of adolescent and young adult oncology. J Oncol Pract 15:235-237, 2019.

2. Miller KD, Fidler-Benaoudia M, Keegan TH, et al: Cancer statistics for adolescents and young adults, 2020. CA Cancer J Clin. September 17, 2020 (early release online).

3. DeSantis CE, Ma J, Gaudet MM, et al: Breast cancer statistics, 2019. CA Cancer J Clin 69:438-451, 2019.

4. Shnorhavorian M, Harlan LC, Smith AW, et al: Fertility preservation knowledge, counseling, and actions among adolescent and young adult patients with cancer: A population-based study. Cancer 121:3499-3506, 2015.

 


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