Secondary Primary Cancer Risk After Radiation Therapy in Rectal Cancer: A Population-Based Cohort Study With Propensity Score Matching

Background: It remains unclear whether radiation therapy (RT) has an impact on the development of secondary primary cancer (SC) in rectal cancer (RC) patients, especially within the true pelvis. Aim: To examine the incidence of SC in a population-based cohort of RC after surgical treatment with or without radiation therapy (RT, NRT). Patients and Methods: The epidemiological cohort consisting of 13,919 RC patients with primary M0 stage diagnosed between 1998 and 2019 was collected from cancer registry data of Upper Bavaria. Competing risk analyses were conducted regarding the development of SC on 11 687 first malignancies, stratified by RT/NRT. A propensity score (PS) was generated by logistic regression modeling of RT to repeat competing risk analyses on a PS-matched cohort. Results: The median age (interquartile range) of the epidemiological cohort was 68.9 years (60.4-76.7). About 60.8%, were men, 38.7% had UICC III, 35.8% of tumors were localized lower than 8 cm, 41.3% underwent RT. Only 17.1% of patients older than 80 years at diagnosis received RT. In general, RT patients were 5 years younger than NRT patients (65.9 years [58.0-73.0] vs. 71.3 years [62.4-79.2], P < .0001). The 20-year cumulative incidence of SC was 16.5% in RT and 17.4% in NRT patients (P = .2298). Men with RT had a lower risk of prostate cancer (HR = 0.55, 95%CI [0.34-0.91], P = .0168). In the PS-matched cohort, RT patients had a significantly higher risk of bladder cancer during follow-up (10-year cumulative incidence of 1.1% vs. 0.6% in NRT). The direction of the RT effects in men and women and different tumor sites may cancel each other. Conclusion: A protective effect of RT in rectal cancer patients on developing prostate SC by half is reproduced. Further analyses studying the long-term SC risks of RT should essentially focus on stratification by sex, and focus on more recent data.