With improvements in survival after colorectal cancer (CRC), more survivors are at risk of developing a second cancer, particularly in younger populations where CRC incidence is increasing. We estimated the incidence of second primary cancer (SPC) in CRC survivors and its potential risk factors. We identified CRC cases diagnosed between 1990 and 2011 and SPCs until 2013 from nine German cancer registries. Standardized incidence ratios (SIR) and absolute excess risk (AER) per 10 000 person‐years were calculated and were stratified by index site: colon cancer (CC) and rectal cancer (RC), age and sex. Cox regression assessed potential SPC risk factors, including primary tumor‐related therapy considering death as a competing risk. We included 217 202 primary CRC cases. SPC occurred in 18 751 CRC survivors (8.6%; median age: 69 years). Risk of cancer was significantly higher in CRC survivors than in the general population (SIR males 1.14, 95% confidence interval [CI] 1.12‐1.17, AER = 24.7; SIR females 1.20, 95% CI 1.17‐1.23, AER = 22.8). Increased risks of SPCs were observed for the digestive system, urinary system and female and male reproductive organs. CRC incidence increased in younger persons (<50 years) and SPC incidence was 4‐fold in this group (SIR males 4.51, 95% CI 4.04‐5.01, AER = 64.2; SIR females 4.03, 95% CI 3.62‐4.48, AER = 77.0). Primary tumor‐related factors associated with SPC risk were right‐sided cancer and smaller primary tumor size. Treatment and risk of SPC differed for CC (no effect) and RC (lower risk after chemotherapy). CRC survivors have excess risk of developing SPC, with particular characteristics that could guide targeted surveillance.

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Background Survival of colorectal cancer (CRC) has improved markedly but risk of an independent second primary cancer (SPC) increases. We determined incidence and potential risk factors of SPC following CRC. Methods We obtained data from 217,202 CRC cases (ICD-10 C18-C20, aged ≥20 years) diagnosed between 1990-2013 from the German Centre for Cancer Registry Data. Cancers arising in a distinct site (excluding non-melanoma skin cancer) and/or of a different histology group were classified as SPCs. Standardised incidence ratios (SIR) and 95% confidence intervals compared the excess risk to the general population, stratified by age, sex and CRC sub-site. Cox proportional hazards models identified potential risk factors of SPC. Results Following CRC (median age 70 years), 18,751 SPCs occurred (8.63%; median age 69 years). SPC incidence increased by 36% in males (SIR: 1.36 [1.34-1.38]), 46% in females (SIR: 1.46 [1.43-1.49]) and doubled for cases &lt;65 years (SIR: 2.08 [1.99-2.17]). Common SPC sites following colon cancer included the small intestine, stomach, liver, pancreas, bladder and kidney. Common male-specific sites included prostate and in females: breast, uterus and ovary. Similar sites were observed following rectal cancer, particularly in cases &lt;65 years. Age, male sex and tumour size (T1, T2) were potential risk factors of SPC. Therapy of CRC (including radiotherapy) did not demonstrate an elevated risk. Conclusions CRC survivors have an increased risk of SPC, particularly due to age, sex and tumour size. Key messages Colorectal cancer survivors have an increased risk of a SPC. Age, sex and tumour size are associated risk factors.