Second primary colorectal cancer in adults: a SEER analysis of incidence and outcomes
Authors: Lun Weijian , Luo Canhua 
Published: July 2023

Abstract
Background
At present, there was no large epidemiological study exploring the actual incidence and survival of second primary colorectal cancer (spCRC). The different characteristics and survival of patients with spCRC and initial primary colorectal cancer (ipCRC) still need to be elucidated. In addition, the factors leading to different survival status of spCRC and ipCRC were still unclear. Our study plan to explore the annual incidence trend of spCRC as well as the factors influencing the occurrence and survival outcome of spCRC.

Methods
This cohort study analyzed the data of 4680 spCRC patients and 330,937 initial primary colorectal cancer (ipCRC) patients. Whether patients had spCRC and whether spCRC patients survived or died were regarded as outcomes. The annual incidence of spCRC from 2004 to 2016 was analyzed by Jointpoint regression analysis. The truncation points were found, and the annual percentage change (APC) of each segment was calculated to explore the trend of spCRC change in the United States. Univariate and multivariable cox regression analyses were conducted to identify factors associated with the occurrence and prognosis of spCRC patients.

Results
The total incidence of spCRC was decreased during 2000–2016 on the whole. The overall incidence of spCRC was lowered in both males and females despite 2013–2014, in the left colon, right colon, rectum and others. The incidence of spCRC was decreased in both 18–49 years’ people and ≥ 50 years’ people during 2000–2016, and the incidence of spCRC in the ≥ 50 years’ people group was higher than those of 18–49 years. Insured (OR = 0.867 (0.778–0.966), initial primary site of other digestive (OR = 0.46, 95%CI: 0.42–0.50), rectum (OR = 0.74, 95%CI: 0.66–0.82), or right colon (OR = 0.73, 95%CI: 0.68–0.79), N 1 stage (OR = 0.87, 95%CI: 0.76–0.99), M 1 stage (OR = 0.49, 95%CI: 0.30–0.80), AJCC II stage (OR = 0.70, 95%CI: 0.60–0.82), AJCC III stage (OR = 0.69, 95%CI: 0.56–0.84), and radiation (OR = 0.69, 95%CI: 0.57–0.83) were associated with the risk of spCRC. At the end of follow-up, 2,246 spCRC patients were survived and 2,434 spCRC patients were dead. Patients with spCRC had poor survival probability than patients with ipCRC. Older age (HR = 1.02, 95%CI: 1.02–1.03), male (HR = 1.13, 95%CI: 1.04–1.23), Black (HR = 1.20, 95%CI: 1.06–1.35), uninsured (HR = 1.36, 95%CI: 1.16–1.59), Signet ring cell carcinoma (HR = 1.64, 95%CI: 1.19–2.25), T4 stage (HR = 1.63, 95%CI: 1.32–2.01), N2 stage (HR = 1.36, 95%CI: 1.08–1.72), M1 stage (HR = 4.51, 95%CI: 2.00–10.18), AJCC III (HR = 1.47, 95%CI: 1.08–1.98), and radiation (HR = 1.82, 95%CI: 1.43–2.33) were associated with increased risk of mortality in spCRC patients.

Conclusion
The incidence of spCRC was decreased except in people with initial primary tumor grade IV and those aged 15–39 years. The overall survival of spCRC patients was lower than ipCRC patients. Cancer patients with older age, high tumor grade, TNM stage, and AJCC stage should be caution to the occurrence of spCRC and timely interventions should be provided for spCRC patients to improve their outcomes.