Risk of Dying From New Cancer Higher in Young Cancer Survivors

Megan Brooks

May 12, 2022

Adolescent and young adult (AYA) cancer survivors face nearly a two-fold higher risk of dying from a new primary cancer compared with peers in the general population, new research shows.

"These findings underscore the critical role of providing high-quality, post-treatment survivorship care to reduce the risk of subsequent cancers," lead investigator Hyuna Sung, PhD, with the American Cancer Society, said in a news release. "Given the younger age at diagnosis, there often should be more opportunities for prevention and early detection of subsequent cancers in this survivor group," Sung added.

The study was published online May 4 in the Journal of the National Cancer Institute.

To date, few studies have explored the risk of new primary malignancies and death among AYA cancer survivors.

In the new analysis, Sung and colleagues set out to better understand this risk. The researchers analyzed data on 170,404 AYA cancer survivors aged 15 to 39 years included in Surveillance, Epidemiology, and End Results (SEER) registries between 1975 and 2013 who survived at least 5 years since their first primary cancer diagnosis.

During a median follow-up of 14.6 years, the authors identified 13,420 subsequent primary cancer cases and 5008 subsequent primary cancer deaths, excluding those attributed to the original cancer site.

Compared with the general population, AYA cancer survivors had a 25% higher incidence and 84% higher risk of dying from a subsequent primary cancer. The absolute excess incidence of and mortality from a subsequent primary cancer was 10.8 and 9.2 per 10,000, respectively.

Risk for a subsequent primary malignancy was statistically significantly higher for 20 of 29 index cancers assessed — most notably among AYA survivors of Hodgkin lymphoma and Kaposi sarcoma in men. Risk for subsequent primary cancer-related death was higher for 26 of 29 index cancers — particularly among AYA survivors of small intestine, eye, and anal cancers.

Overall, subsequent primary cancer of the breast, lung, and colorectum made up 36% of all cases and 39% of all deaths. Breast cancer accounted for the most cases (18%), followed by lung (11%), colorectum (7.6%), and prostate (7.1%), while lung cancer was the leading cause of death (24%), followed by breast (8.6%), colorectal (6.9%), and pancreatic (6.8%) cancers.

"Our findings highlight the need to expand the emphasis on [subsequent primary cancer] surveillance to include AYA as well as childhood cancer survivors and to develop age-specific and risk-appropriate surveillance strategies," Sung and colleagues conclude.

"Sobering" Data, Time for Action

The finding that AYA survivors were nearly twice as likely to die from a new cancer than the general population is a "sobering finding that warrants reflection," oncologists Danielle Novetsky Friedman, MD, with Memorial Sloan Kettering Cancer Center, New York City, and Tara Henderson, MD, with the University of Chicago, Illinois, write in an accompanying editorial.

Friedman and Henderson point out that multiple factors may contribute to an increased risk for subsequent primary cancers, including previous treatment exposures, distinctive tumor biology and genomic characteristics, as well as the unique health and psychosocial needs of AYA cancer survivors.

Gaining a better understanding of mechanistic underpinnings of this increased risk "can inform novel approaches to modify late outcomes in this cohort," the editorialists add.

Ongoing surveillance is essential as well. Cancers of the breast, lung, and colorectum — which make up more than one third of all subsequent primary cancers and nearly 40% of related deaths — are all "potentially preventable by early detection methods and/or modification of key lifestyle behaviors."

Overall, the current analysis "provides an important call to action for clinicians and researchers to think carefully and creatively about next steps to rectify this problem," the editorialists write.

Funding for the study was provided by the American Cancer Society and the Medical College of Wisconsin (MCW) Cancer Center. One study author serves on the Flatiron Health Equity Advisory Board. Sung, Friedman, and Henderson have disclosed no relevant financial relationships.

J Natl Cancer Inst. 2022;djac091, djac093. Abstract, Editorial

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