Risk Factors, Cancer Types and Prognostic Significance of Second Primary Cancer After Early-, Intermediate- and Late-Onset Colorectal Cancer: A Retrospective Study in a Chinese High-Volume Cancer Center

The incidence of early-onset colorectal cancer (EOCRC) is increasing worldwide, and CRC survivors may have an elevated risk of second primary cancer (SPC). This retrospective study analyzed 13,302 CRC patients diagnosed between 2008 and 2018 at a Chinese high-volume cancer center, including 635 (4.77%) who developed SPC after CRC. Patients were stratified by age at CRC diagnosis (<50, 50-69, and ≥70 years) to identify risk factors, cancer types, and prognostic significance of SPC. Multivariable Cox analysis showed that older age, neoadjuvant therapy, tumor location, T stage, N stage, M stage, and radiotherapy were independently associated with SPC in the overall cohort. Age-stratified analyses revealed heterogeneous associated factors, with radiotherapy being the only independent factor in the ≥70-year group. Five-year overall survival was comparable between the <50- and 50-69-year groups and was significantly better than in the ≥70-year group among all CRC patients and those with SPC. Early-stage patients with SPC had better overall survival than those without SPC, whereas advanced-stage patients without SPC had better survival. These findings suggest age-specific heterogeneity in SPC development and support tailored surveillance strategies after CRC.