Adolescent and Young Adult Cancer Survivors Face Higher Risk of Second Cancers

People who were diagnosed with cancer as adolescents or young adults (AYAs) have an excess risk of developing a subsequent primary neoplasm later in life, compared with the general population, according to findings from a large-scale study published in Lancet Oncology. Among 16 types of cancer studied, Hodgkin lymphoma (HL) appeared to be associated with the greatest risk of developing a second cancer.

The authors, led by Chloe J. Bright, MD, from the Centre for Childhood Cancer Survivor Studies at the Institute of Applied Health Research at the University of Birmingham in the U.K., also observed that a small number of specific cancers – including lung cancer – accounted for most of the total excess number of secondary neoplasms.

“The prominence of lung cancer after each of these AYA cancers indicates the need for further work aimed at preventing and reducing the burden of this cancer in future survivors of AYA cancer,” the researchers noted, adding that “[our study] provides an evidence base to inform priorities for clinical long-term follow-up.”

To characterize the risks of developing secondary cancers among this population, the authors collected information from the Teenage and Young Adult Cancer Survivor Study, a population-based cohort of 200,945 patients living in England and Wales who were diagnosed with cancer between the ages of 15 and 39. Participants were followed from five years after diagnosis until death, emigration, or study end date (December 31, 2012).

In this analysis, researchers focused on the risk of specific subsequent primary neoplasms after 16 types of AYA cancer: breast, cervical, testicular, HL (separate categories for male and female patients), melanoma, central nervous system tumors, colorectal, non-HL, thyroid, soft-tissue sarcoma, ovarian, bladder, other female genital, leukemia, and head and neck cancer.

Standardized incidence ratios (SIRs) were calculated by comparing observed numbers of neoplasms divided by expected numbers; expected incidence was derived from the corresponding cancer rate among age- and sex-matched controls in the general population.

Next, absolute excess risks (AERs) were calculated as the excess number of subsequent primary neoplasms beyond those expected from the general population and reported as neoplasms per 10,000 patient-years.

Median follow-up for each participant was 16.8 years (interquartile range = 10.5-25.2 years), and patients were followed for a total of 2,631,326 person-years.

During this time, 12,321 subsequent primary neoplasms were diagnosed in 11,565 survivors, most frequently among survivors of breast cancer, cervical cancer, testicular cancer, and HL (TABLE).

For patients with HL, the AER of any subsequent primary neoplasm in women was 56 excess subsequent primary neoplasms per 10,000 person-years, corresponding to an SIR of 3.1. In men, the AER was 30 per 10,000 person-years and the SIR was 2.6.

“The excess number of subsequent pri-mary neoplasms observed increases with increased period of follow-up from diagnosis after each AYA cancer investigated,” the authors reported. At 30 years or longer after diagnosis of HL, for example, the AER for any subsequent primary neoplasm reached 168.6 per 10,000 person-years in women and 121.9 per 10,000 person-years in men.

In survivors of other AYA cancers, lung cancer was the most commonly observed subsequent cancer: The cumulative incidence of lung neoplasms at 35 years after the initial HL diagnosis was 3.8 percent for women and 5.1 percent for men, compared with expected incidences of 0.9 percent and 1.4 percent in the general population. Lung cancer also accounted for 15.4 percent and 41.2 percent of the total number of excess neoplasms in men and women with HL, respectively.

Across the entire cohort of survivors, “the burden of the excess number of neoplasms … accounted for by lung cancer was substantial and apparent across all AYA cancers investigated,” they added. Smoking status contributed to this excess risk, but the authors also noted that the risk of developing second cancers has been shown to be elevated in patients who have been treated with radiation therapy or chemotherapy.

“The evidence presented in our study, along with previous literature on smoking in cancer survivors, clearly suggests that clinical follow-up of survivors of AYA cancer, particularly survivors of breast cancer, cervical cancer, and HL, should focus on subsequent lung cancer and provision of smoking cessation advice,” the authors commented.

The study’s implications are limited by its reliance on data from a cancer registry that did not contain detailed treatment information. Also, these results might not be generalizable to patients outside of the U.K. “We are planning to conduct case-control studies with detailed treatment dosimetry, questionnaires for lifestyle and other relevant factors, and saliva collection for genotypic factors,” the authors noted.

The authors report no relevant conflicts of interest.


Bright CJ, Reulen RC, Winter DL, et al. Risk of subsequent primary neoplasms in survivors of adolescent and young adult cancer (Teenage and Young Adult Cancer Survivor Study): a population-based, cohort study. Lancet Oncol. 2019;20:531-45.