Large Study Sheds Light on Risks for Second Cancers Among Young Survivors

Among survivors of adolescent and young adult cancers, several specific malignancies account for the bulk of excess risk for subsequent primary neoplasms, according to a large study. Lung cancer in particular accounts for a substantial portion of the subsequent malignancies.

In Europe, the 5-year relative survival after adolescent and young adult (AYA) cancer is 82%. “Survivors are at increased risk of developing subsequent primary neoplasms, estimated to be between 1.5 and 3.1 times higher than that expected from the general population,” wrote study authors led by Chloe J. Bright, PhD, of the University of Birmingham in the United Kingdom. “Treatment of AYA cancer varies greatly by cancer type and therefore, in the absence of detailed treatment information, it is essential to stratify risks by specific types of AYA cancer; such risk stratification provides an evidence base for clinical follow-up.”

The Teenage and Young Adult Cancer Survivor Study (TYACSS) included a total of 200,945 survivors of cancer that was diagnosed between the ages of 15 and 39 years in England and Wales, between 1971 and 2006. The new analysis focused on survivors of 16 types of AYA cancer, covering a total of 197,827 survivors and 2,631,326 person-years of follow-up (median, 16.8 years). The results were published in Lancet Oncology.

There were a total of 12,321 subsequent primary neoplasms diagnosed in 11,565 survivors (6%). Subsequent primary neoplasms were most frequently diagnosed in survivors of breast cancer (15%), cervical cancer (14%), Hodgkin lymphoma (13%), and testicular cancer (12%).

The researchers calculated the absolute excess risk (AER) for survivors of each type of primary cancer. Among the highest AERs were that for Hodgkin lymphoma, at 55.7 per 10,000 person-years among female survivors and 29.9 per 10,000 person-years among males; colorectal cancer, at 32.1 and 28.9 per 10,000 person-years among female and male survivors, respectively; and breast cancer, at 19.5 per 10,000 person-years. The cumulative incidence of all types of subsequent cancers 35 years after the initial diagnosis was 11.9% in survivors of breast cancer, 20.2% in those who had testicular cancer, and 26.6% and 16.5% in female and male survivors of Hodgkin lymphoma.

Certain subsequent primary neoplasms accounted for large proportions of those diagnosed. Lung cancer alone accounted for 45% of the total number of excess neoplasms among patients who had survived for at least 30 years. At 35 years, the cumulative incidence of a subsequent primary lung cancer was 2.9%, compared with an expected incidence of 2.0%. Across survivors of cervical cancer, testicular cancer, Hodgkin lymphoma in women, breast cancer, and Hodgkin lymphoma in men, the study found a small number of subsequent neoplasms could account for 82%, 61%, 58%, 45%, and 41%, respectively, of all subsequent cancers.

“Our findings provide an evidence base for clinical follow-up relating specifically to the AYA population,” the authors wrote.

In an accompanying editorial, Sumit Gupta, MD, of the Hospital for Sick Children in Toronto, wrote that “the level of granularity provided in the risk estimates … should assist clinicians and policy makers in determining what type of interventions would be of greatest benefit for specific populations of AYA cancer survivors.” He pointed out several limitations to the data, including in particular the lack of treatment data; given that late effects are most closely associated with the types and doses of therapy, this limits the interpretation of these results.

“Description of risk is only a first step towards the ultimate goal of improving the quantity and quality of life for survivors of AYA cancer,” he wrote. “Studies that identify effective interventions for this population, whether in the prevention, screening, or treatment of late effects, are crucial.”