Risk Factors of Multiple Primary Cancers Among Colorectal Cancer Survivors

Background: Colorectal cancer (CRC) is the most common cancer and the leading cause of cancer-related death globally. While survival improved, CRC patients face the risk of subsequent multiple primary cancers (MPCs). This study aimed to determine the incidence and identify risk factors associated with metachronous MPCs among CRC survivors. Methods: A retrospective analysis was performed on adults diagnosed with invasive colorectal adenocarcinoma at Flinders Medical Centre from 2011 to 2024, who had at least 6 months of post-CRC follow-up. Sociodemographic factors, clinical information, tumour characteristics, and treatment types were collected. Cumulative incidence function and sub-distribution hazard models were used to estimate the incidence and identify risk factors of developing MPCs. Results: Of the total 554 eligible study participants, 12% developed MPC, with a median follow-up time of 5 years (interquartile range: 2.8-7.6 years) until the diagnosis of MPC. Gastrointestinal, prostate, and haematological malignancies were the most common types of MPCs identified. The cumulative incidence and standardised incidence ratio (SIR) of an MPC were 20.9% (95% CI: 15.3-25.6) and 1.32 (95% CI: 1.03-1.68), respectively. Male sex, older age (>65 y), early-stage cancer, and loss of mismatch repair (MMR) protein expression were associated with an increased risk of developing MPCs. Conclusions: CRC survivors have a higher risk of developing an MPC compared to the general population. Sex, age, cancer stage, and MMR protein expression are factors associated with MPCs. Therefore, tailored surveillance based on the individual's risk profile should be considered for timely diagnosis of subsequent cancers to improve long-term outcomes.