AYA cancer survivors at higher risk for death due to second primary cancers


Disclosures: American Cancer Society and Medical College of Wisconsin Cancer Center supported the study. Sung reports no relevant financial disclosures. Please see the study for all authors’ relevant financial disclosures.

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Death due to a second primary cancer occurred nearly twice as often among adolescent and young adult cancer survivors compared with the general population, according to study results published in Journal of the National Cancer Institute.

The findings highlight the need for primary care cancer prevention and ongoing cancer surveillance strategies for this patient population, researchers noted.

Risk for death among younger patients.
Data derived from Sung H, et al. J Natl Cancer Inst. 2022;doi:10,1093/jnci/djac091.

Rationale and methods

Subsequent primary cancer research has been most extensively conducted among survivors of childhood cancers but relatively less is known about survivors of older age groups,” Hyuna Sung, PhD, principal scientist at American Cancer Society, told Healio. “In our previous study published in 2020, we examined the risk for a subsequent primary cancer among survivors of adult-onset cancer, and this is a follow-up study to that research.”

The study included 170,404 cancer survivors aged 15 to 39 years included in SEER registries between 1975 and 2013 who were at least 5 years out from a first primary cancer diagnosis.

Researchers compared cancer incidence and mortality among the survivors with that of the general population using standardized incidence ratio (SIR), absolute excess incidence, standardized mortality ratio (SMR) and absolute excess mortality.

Mean follow-up was 14.6 years.

Key findings

Researchers identified 13,420 second primary cancer cases and 5,008 second primary cancer-associated deaths among cancer survivors, which corresponded to a 25% higher cancer incidence (SIR = 1.25; 95% CI, 1.23-1.27) and an 84% higher cancer-associated mortality (SMR = 1.84; 95% CI, 1.79-1.89) than the general population.

Risk for second primary cancer appeared statistically higher among survivors for 20 of 29 index cancers, including female Hodgkin lymphoma (SIR = 3.05; 95% CI, 95% CI, 2.88-3.24) male Kaposi sarcoma (SIR = 2.58; 95% CI , 2.18-3.03) and male Hodgkin lymphoma (SIR = 2.24; 95% CI, 2.09-2.41). Risk for mortality appeared higher among survivors for 26 index cancers, including small intestine cancer (SMR = 6.97; 95% CI, 4.8- 9.79), eye cancer (SMR = 6.53; 95% CI, 5.06-8.29) and anal cancer (SMR = 6.34; 95% CI, 4.25-9.11).

Overall, second primary cancers of the female breast, lung and colorectum made up 36% of all second primary cancer cases and 39% of all second primary cancer deaths. Lung cancer constituted 11% of all cases and 24% of all deaths.

Hyuna Sung, PhD

Hyuna Sung

Survivors overall had twice the risk for death from a new cancer diagnosis compared with the expected cancer mortality in the general population, yet the risk varied substantially,” Sung said. “For example, the risk was five times higher among Hodgkin lymphoma survivors and about twofold higher among survivors of brain, head and neck, breast or colorectal cancers. This increased mortality reflects not just increased risk but also poor cancer survival when patients were treated for subsequent cancer. Contrarily, the risk estimated for thyroid or melanoma cancer survivors did not differ from the general population. This large variation by cancer type indicates differences in exposures to prior cancer treatment and risk factors across survivor groups, highlighting the need for targeted prevention strategies.”


Adolescent and young adult cancer survivors face a long survivorship phase, often spanning several decades, Sung said.

“Given their younger age at diagnosis, there often should be more opportunities for prevention and early detection of subsequent cancers in this survivor group,” she added. “Many survivors, however, are often less prepared and more overwhelmed with the shift into survivorship once treatment is finished.”

Access to easily understood information about the long-term risks associated with cancer treatment and risks for subsequent cancer and other late effects should be available to any individual with a history of cancer, Sung said.

“More research is needed to refine the risk estimates based on survivors’ history of treatment and cancer risk factors, as well as to develop models to deliver equitable and survivor-centered care to minimize the risk for a second primary cancer and maximize wellness as survivors age,” she said.


Sung H, et al. JAMA. 2020;doi:10.1001/jama.2020.23130.
Sung H, et al. J Natl Cancer Inst. 2022; doi:10.1093/jnci/djac091.

For more information:

Hyuna Sung, PhD, can be reached at American Cancer Society, 250 Williams St., Atlanta, GA 30303; email: hyuna.sung@cancer.org.

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