Systemic Chemotherapy for Metastatic Colitis-Associated Cancer has a Worse Outcome than for Sporadic Colorectal Cancer: a Matched Case Cohort Analysis

Abstract Background Colitis-associated Cancers (CAC) are a catastrophic complication of Inflammatory Bowel Disease (IBD); at diagnosis, CAC is frequently at an advanced stage. Although the genomic alterations (GA) in CAC are different from sporadic colorectal cancer (CRC), the same systemic therapies are used. We compared clinically relevant outcomes using standard care systemic chemotherapy of Stage IV CAC versus a matched patient control cohort of Stage IV CRC patients. Methods A retrospective matched cohort design was used.18 cases with Stage IV CAC (7 UC; 11 CD) and 18 CRC were identified. GA analysis was available for all patients. Outcome endpoints included response rate and response duration, Progression-free Survival (PFS), and Overall Survival. Results While the response rates were similar (CAC 35.7% vs CRC 57.1%, p=0.45), the median duration of response for CAC was significantly shorter (1.4 months vs. CRC 11.8 months, p=0.006). There was no difference in dose density of first line therapy between cohorts, suggesting that shorter response duration was due to more rapid development of chemotherapy resistance. Median OS was significantly shorter for CAC patients (13 vs 27.6 months), p=0.034. As expected, there was a difference in the spectrum of GA between CAC and CRC cohorts. However, GA associated with poor prognosis (eg B-Raf) were no more frequent in the CAC cohort. Conclusions Clinically meaningful outcomes of duration of response and overall survival are worse for CAC vs sporadic CRC patients treated with FOLFOX or FOLFIRI as first therapy for metastatic disease.