Risk of Developing Subsequent Primary Colorectal Cancers Among Non-Colorectal Cancer Survivors: Implications for Prevention and Screening.

Cancer survivors have an elevated risk of developing subsequent primary cancers, including colorectal cancer (CRC), and may benefit from tailored screening approaches to reduce incidence and morbidity. A retrospective cohort of adults diagnosed with cancer (excluding CRC) in Alberta, Canada from 2000 to 2021 who survived at least 6 months was used to investigate the incidence of CRC compared to the cancer-free population. Incidence rate differences and standardized incidence ratios (SIRs) were used to characterize risk across first primary cancer sites, sexes, age groups, and survivorship periods, as well as according to CRC stage, histology, and subsite. Multivariable Fine-Gray models were used to identify risk factors within site-specific survivorship groups. Among 172,928 cancer survivors, 1812 were diagnosed with CRC during a median follow-up of 4.9 years. Compared to the cancer-free population, survivors had an elevated risk of CRC (SIR = 1.26, 95% CI: 1.20-1.32). The risk of CRC varied across first primary cancer sites but remained elevated among both short- and long-term survivors. Cancer survivors were at an elevated risk of developing late stage (III/IV) CRC compared to the cancer-free population with the highest risk in the proximal colon and among long-term survivors (5+ years). Depending on the first primary cancer site, risk factors for subsequent CRC included older age at diagnosis, male sex, overweight/obese body mass index, earlier stage at diagnosis, and treatment type. These findings demonstrate the importance of improving adherence to CRC screening guidelines among cancer survivors. Greater research is needed to identify high-risk survivorship groups who may require enhanced screening.