Survivors of adolescent and young adult (AYA) cancers have almost twice the risk of dying from a subsequent primary cancer (SPC) as the general population, according to a study published in the Journal of the National Cancer Institute

Researchers found that AYA cancer survivors had a 25% higher risk of developing SPCs and an 84% higher risk of dying from SPCs, when compared with expected risks in the general population.  

The risk of SPC incidence remained significantly elevated for 20 years or more for 9 of the cancers studied, and the risk of SPC death remained elevated for 20 years or more for 20 of the cancers.

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The study included 170,404 AYAs (aged 15 to 39 years) with 29 index cancers. The most common diagnoses were breast cancer, melanoma, thyroid cancer, and testicular cancer. All patients had survived at least 5 years from diagnosis. The patient data were taken from SEER registries and compared with the general population. 

During a mean follow-up of 14.6 years, there were 13,420 SPC cases and 5008 SPC deaths among the cancer survivors. 

The most common SPCs were breast (17.8%), lung (10.8%), colorectal (7.6%), and prostate (7.1%) cancers. The most common causes of SPC death were lung (23.7%), breast (8.6%), colorectal (6.9%), and pancreatic (6.8%) cancers.

When compared with the general population, the risk of SPC incidence was significantly higher for 20 of the 29 index cancers. The highest standardized incidence ratio was observed for female Hodgkin lymphoma (3.05; 95% CI, 2.88-3.24). 

The risk of SPC mortality was higher for 26 of the 29 cancers. The highest standardized mortality ratio was seen for cancer of the small intestine (6.97; 95% CI, 4.80-9.79). 

The risks of developing and dying from lung cancer were significantly elevated among survivors of lymphoma and cancers of the breast, anus, vagina/vulva, head and neck, urinary bladder, and cervix. 

The risks of developing and dying from breast cancer were significantly higher among survivors of lymphomas and sarcomas. 

The risk of developing colorectal cancer was significantly higher among survivors of small intestine, corpus uterine, cervical, testicular, and ovarian cancer as well as Hodgkin lymphoma. The increased risk of death was significant for all but ovarian cancer and female Hodgkin lymphoma. 

“Our findings highlight the need to expand the emphasis on SPC surveillance to include AYA as well as childhood cancer survivors and to develop age-specific and risk-appropriate surveillance strategies for SPCs in this growing population of survivors,” the researchers wrote.


Sung H, Siegel RL, Hyun N, et al. Subsequent primary cancer risk among five-year survivors of adolescent and young adult cancers. J Natl Cancer Inst. Published online May 4, 2022. doi:10.1093/jnci/djac091