Abstract PR005: Outcomes in colitis-associated metastatic colorectal cancer and intersection with early-onset and signet ring cell carcinoma
Authors: Villarreal Oscar E. , Zeineddine Fadl , Chacko Ray , Parseghian Christine , Johnson Benny , Willis Jason , Lee Michael , Morris Van Karlyle , Dasari Arvind , Raghav Kanwal , Overman Michael , You Y. Nancy , Wang Yinghong , Maru Dipen , Shen John Paul , Kopetz Scott 
Published: December 2022

Abstract
Patients with inflammatory bowel disease (IBD) have a higher risk of developing colorectal cancer (CRC) and mortality from colitis-associated CRC (CA-CRC) is currently rising. Clinical and molecular differences between CA-CRC and sporadic-CRC (S-CRC) have been previously identified, however there are conflicting reports on outcomes of CA-CRC, especially for those with metastatic CRC (mCRC). Due to the earlier onset of CA-CRC, undiagnosed IBD has been speculated to be a contributing factor to the rising prevalence of early-onset CRC (EOCRC), but confirmatory studies are lacking. In this retrospective study, three independent CRC patient datasets from MDACC were used – the mATTACC discover cohort (n=32 CA-mCRC; n=425 S-mCRC), a tumor registry (n=1696, excluding MSI-High samples), and a real-world evidence (RWE) validation dataset (n=269 CA-mCRC; n=29,596 S-mCRC). These cohorts were analyzed in order to explore characteristics of patients with CA-mCRC, evaluate the amount of EOCRC attributable to CA-mCRC, and compare outcomes of patient populations with CA-mCRC. Median age at diagnosis for patients with CA-mCRC (48yo) was significantly lower compared to S-mCRC (58yo; p&lt;0.001), and an association between CA-mCRC and EOCRC was confirmed (OR=4.04, p&lt;0.001). Prevalence of signet ring cell and mucinous (SRC/M) histology, a rare subtype of CRC, was analyzed within CA-mCRC and EOCRC cases in our cohorts. SRC/M histology was present in 28%-39% of CA-mCRC and 13%-15% of EOCRC cases, thus confirming the strong association of SRC/M histology with both CA-mCRC (OR=3.13, p&lt;0.001) and EOCRC (OR=1.35, p&lt;0.001). Therefore, by comparing the frequency of SRC/M in EOCRC and late-onset CRC, and correcting by the proportion of CA-mCRC cases with SRC/M histology, we estimate between 8.3% to 10.2% of EOCRC may be due to undiagnosed or subclinical IBD. Median overall survival (mOS) for patients with CA-mCRC (31m) was lower relative to S-mCRC (39m; HR=1.26, 95%CI: 1.06-1.48). In EOCRC, patients with CA-mCRC had worse outcomes (mOS=25m) compared to S-mCRC (40m; HR=1.61, 95%CI: 1.23-2.11). Prevalence of SRC/M histology stratified by CA-mCRC or EOCRC status revealed an increasing trend of SRC/M occurrence specifically within CA-mCRC (1995-2015). Additionally, for patients with CA-mCRC the mOS for those with SRC/M (21m) was lower than those with mucinous (51m) histology, highlighting the poor prognosis of SRC/M in this patient population (HR=1.89, 95%CI: 1.06-3.33). Patients with CA-mCRC have worse outcomes than S-mCRC, and those with early-onset or SRC/M have lower survival rates. Tumor biology consistent with CA-CRC, including SRC/M histology, may be present in 8.3%–10.2% of patients with EOCRC without a clinical diagnosis of IBD. Although other confounding biology may be underlying this association, recognition of undiagnosed IBD in mCRC patients is important as it may impact prognosis and treatment strategies for this high-risk patient population.
Citation Format: Oscar E. Villarreal, Fadl Zeineddine, Ray Chacko, Christine Parseghian, Benny Johnson, Jason Willis, Michael Lee, Van Karlyle Morris, Arvind Dasari, Kanwal Raghav, Michael Overman, Y. Nancy You, Yinghong Wang, Dipen Maru, John Paul Shen, Scott Kopetz. Outcomes in colitis-associated metastatic colorectal cancer and intersection with early-onset and signet ring cell carcinoma [abstract]. In: Proceedings of the AACR Special Conference on Colorectal Cancer; 2022 Oct 1-4; Portland, OR. Philadelphia (PA): AACR; Cancer Res 2022;82(23 Suppl_1):Abstract nr PR005.