Risk of Subsequent Primary Cancers Among Adult-Onset 5-Year Cancer Survivors in South Korea: Retrospective Cohort Study

Background The number of cancer survivors who develop subsequent primary cancers (SPCs) is expected to increase. Objective We evaluated the overall and cancer type–specific risks of SPCs among adult-onset cancer survivors by first primary cancer (FPC) types considering sex and age. Methods We conducted a retrospective cohort study using the Health Insurance Review and Assessment database of South Korea including 5-year cancer survivors diagnosed with an FPC in 2009 to 2010 and followed them until December 31, 2019. We measured the SPC incidence per 10,000 person-years and the standardized incidence ratio (SIR) compared with the incidence expected in the general population. Results Among 266,241 survivors (mean age at FPC: 55.7 years; 149,352/266,241, 56.1% women), 7348 SPCs occurred during 1,003,008 person-years of follow-up (median 4.3 years), representing a 26% lower risk of developing SPCs (SIR 0.74, 95% CI 0.72-0.76). Overall, men with 14 of the 20 FPC types had a significantly lower risk of developing any SPCs; women with 7 of the 21 FPC types had a significantly lower risk of developing any SPCs. The risk of developing any SPC type differed by age; the risk was 28% higher in young (<40 years) cancer survivors (SIR 1.28, 95% CI 1.16-1.42; incidence: 30 per 10,000 person-years) and 27% lower in middle-aged and older (≥40 years) cancer survivors (SIR 0.73, 95% CI 0.71-0.74; incidence: 80 per 10,000 person-years) compared with the age-corresponding general population. The most common types of FPCs were mainly observed as SPCs in cancer survivors, with lung (21.6%) and prostate (15.2%) cancers in men and breast (18.9%) and lung (12.2%) cancers in women. The risks of brain cancer in colorectal cancer survivors, lung cancer in laryngeal cancer survivors, and both kidney cancer and leukemia in thyroid cancer survivors were significantly higher for both sexes. Other high-risk SPCs varied by FPC type and sex. Strong positive associations among smoking-related cancers, such as laryngeal, head and neck, lung, and esophageal cancers, were observed. Substantial variation existed in the associations between specific types of FPC and specific types of SPC risk, which may be linked to hereditary cancer syndrome: for women, the risks of ovarian cancer for breast cancer survivors and uterus cancers for colorectal cancer survivors, and for men, the risk of pancreas cancer for kidney cancer survivors. Conclusions The varying risk for SPCs by age, sex, and FPC types in cancer survivors implies the necessity for tailored prevention and screening programs targeting cancer survivors. Lifestyle modifications, such as smoking cessation, are essential to reduce the risk of SPCs in cancer survivors. In addition, genetic testing, along with proactive cancer screening and prevention strategies, should be implemented for young cancer survivors because of their elevated risk of developing SPCs.