Young Cancer Survivors Face Higher Risk of Death From Second Malignancies

Adolescent and young adult (AYA) cancer survivors have a significantly increased risk for developing a new cancer and dying from that cancer, according to a population-based study.

These younger cancer survivors had a 25% higher risk for cancer incidence, and an 84% higher risk for cancer death, compared with the general population, reported Hyuna Sung, PhD, of the American Cancer Society, and colleagues.

Among over 170,000 survivors ages 15 to 39 at the time of first primary diagnosis who had survived for at least 5 years, 13,420 subsequent primary cancers, and 5,008 deaths, occurred over a mean follow-up of 14.6 years, they noted in the Journal of the National Cancer Institute.

“Research on subsequent primary cancers has mainly focused on pediatric cancer survivors,” Sung told MedPage Today. “This study highlights the need for targeted prevention strategies not only for pediatric cancer survivors, but AYA survivors as well.”

Breast cancer accounted for 17.8% of subsequent primary cancers, followed by lung (10.8%), colorectal (7.6%), and prostate (7.1%) cancers. Lung cancer was the leading cause of death (23.7%), followed by breast (8.6%), colorectal (6.9%), and pancreatic (6.8%) cancers.

The overall risk of developing a subsequent primary cancer was statistically significantly higher for 20 of the 29 index cancers evaluated in the study, and remained elevated for 20 or more years postdiagnosis for nine of the cancers. The mortality risk was statistically significantly higher for 26 cancers, and remained elevated for 20 or more years after diagnosis for 20 of the cancers.

Of the four most common index cancers, the risk of developing a subsequent primary cancer compared with the general population was significantly higher for breast cancer (standardized incidence ratio [SIR] 1.31, absolute excess incidence [AEI] 12.1 per 10,000) and testicular cancer (SIR 1.21, AEI 7.9 per 10,000). This risk was not different among thyroid cancer survivors, and was statistically significantly lower among melanoma survivors (SIR 0.87, AEI -6.2 per 10,000).

Similarly, the risk of dying from a subsequent primary cancer was significantly elevated among breast cancer survivors (standardized mortality ratio [SMR] 1.79, absolute excess mortality [AEM] 9.2 per 10,000) and testicular cancer survivors (SMR 1.74, AEM 7.8 per 10,000), with no difference among thyroid cancer and melanoma survivors.

For individual cancers, the highest SIRs were for females with Hodgkin lymphoma (SIR 3.05), males with Kaposi sarcoma (SIR 2.58), and males with Hodgkin lymphoma (SIR 2.24), with cumulative incidence rates after 35 years of 25.9%, 13.7%, and 18.8%, respectively.

The highest SMRs were seen for small intestine cancer (SMR 6.97), eye cancer (SMR 6.53), and anal cancer (SMR 6.34).

For this study, Sung and colleagues used population-based cancer incidence and mortality data from nine Surveillance, Epidemiology, and End Results Program (SEER) registries. Follow-up began 5 years from initial cancer diagnosis and continued until censoring at death, loss to follow-up, or Dec. 31, 2018, whichever came first, while the cumulative incidence and mortality rates of subsequent primary cancers were calculated at 35 years after the index cancer diagnosis.

Even with long-term follow-up, events were rare for some subsequent primary cancers, the authors noted. In addition, restricting the analysis to subsequent cancers that occurred 5 or more years after the initial diagnosis “likely underestimated” the risk for some cancers, “particularly treatment-related acute myeloid leukemia or myelodysplastic syndromes, which typically arise after a short-term latency,” they wrote.

As for future areas of research, Sung said that while the study quantified risk estimates, “they should be refined based on treatment history and potential cancer risk factors. There should also be more research to develop models to deliver more equitable and survivor-centric care.”