Clinicopathological and molecular differences between stage IV screen-detected and interval colorectal cancers in the Flemish screening program

Abstract

Introduction: Interval cancer (IC) is an important quality indicator in colorectal cancer (CRC) screening. Previously, we found that fecal immunochemical test (FIT) ICs are more common in women, older age, right-sided tumors, and advanced stage. Here, we extended our existing stage IV patient cohort with clinicopathological and molecular characteristics, to identify factors associated with FIT-IC.

Methods: Logistic regression models were fit to identify variables associated with the odds of having a stage IV FIT-IC. Multivariate models were corrected for gender, age, and location.

Results: A total of 292 screen-detected (SD) CRCs and 215 FIT-IC CRCs were included. FIT-IC CRC had 5 fold higher odds to be a neuroendocrine (NET) tumor and 2.5 fold higher odds to have lymphovascular invasion. Interestingly, some variables lost significance upon accounting for location. Thus, tumor location is a critical covariate that should always be included when evaluating factors related to FIT-IC.

Conclusions: We identified NETs and lymphovascular invasion as factors associated with increased odds of having a stage IV FIT-IC. Moreover, we highlight the importance of tumor location as a covariate in evaluating FIT-IC related factors. More research across all stages is needed to clarify how these insights might help to optimize the Flemish CRC screening program.

Keywords: clinicopathological differences; colorectal cancer; interval cancer; molecular alterations; screening.

Figure 1

Adjusted Odds Ratio with 95% confidence intervals for variables associated with stage IV FIT-IC. LVI, lymphovascular invasion; NET, neuro-endocrine tumor; Ca, carcinoma. Figure created with Graphpad Prism v10.1.1.