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

Abstract

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 primarycancer (FPC) types considering sex and age. Methods: We conducted a retrospective cohort study using the Health Insurance Review and Assessment database of SouthKorea 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 incidenceexpected 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 during1,003,008 person-years of follow-up (median 4.3 years), representing a 26% lower risk of developing SPCs (SIR 0.74, 95% CI0.72-0.76). Overall, men with 14 of the 20 FPC types had a significantly lower risk of developing any SPCs; women with 7 ofthe 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 10,000person-years) compared with the age-corresponding general population. The most common types of FPCs were mainly observedas SPCs in cancer survivors, with lung (21.6%) and prostate (15.2%) cancers in men and breast (18.9%) and lung (12.2%) cancersin women. The risks of brain cancer in colorectal cancer survivors, lung cancer in laryngeal cancer survivors, and both kidneycancer and leukemia in thyroid cancer survivors were significantly higher for both sexes. Other high-risk SPCs varied by FPCtype and sex. Strong positive associations among smoking-related cancers, such as laryngeal, head and neck, lung, and esophagealcancers, were observed. Substantial variation existed in the associations between specific types of FPC and specific types of SPCrisk, which may be linked to hereditary cancer syndrome: for women, the risks of ovarian cancer for breast cancer survivors anduterus 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 tailoredprevention and screening programs targeting cancer survivors. Lifestyle modifications, such as smoking cessation, are essentialto reduce the risk of SPCs in cancer survivors. In addition, genetic testing, along with proactive cancer screening and preventionstrategies, should be implemented for young cancer survivors because of their elevated risk of developing SPCs