Up to 10% of Early-Onset mCRC Cases May Be Driven by Undiagnosed IBD

Colon cancer, computer illustration.
As many as 10% of early-onset metastatic colorectal cancer cases may be attributable to undiagnosed inflammatory bowel disease, a study suggests.

As many as 10% of early-onset metastatic colorectal cancer (mCRC) cases may be attributable to undiagnosed inflammatory bowel disease (IBD), according to a study presented at the 2022 AACR Special Conference: Colorectal Cancer.1  

The study also showed that colitis-associated mCRC is associated with shorter overall survival (OS) among patients with early-onset mCRC.

It’s important to recognize these high-risk patients, given the potential implications for prognosis and treatment decisions, according to study presenter Oscar E. Villarreal, PhD, of The University of Texas MD Anderson Cancer Center in Houston.

Dr Villarreal explained that patients with IBD have an elevated risk of CRC. Some studies indicate that the prognosis for colitis-associated CRC is worse than for sporadic CRC, but few studies have focused specifically on patients with colitis and metastases from their cancer.2

Since patients with colitis-associated CRC tend to be younger than patients with sporadic CRC, some investigators have speculated that part of the rising prevalence of early-onset CRC may be due to unrecognized colitis in younger individuals.

Dr Villarreal and colleagues sought to determine what proportion of early-onset mCRC might be attributable to undiagnosed IBD and whether there were survival differences between patients with colitis-associated mCRC and those with sporadic mCRC.

The researchers analyzed a discovery cohort consisting of patients from the tumor registry at MD Anderson Cancer Center. The cohort included 32 patients with colitis-associated mCRC and 397 with sporadic mCRC. 

The study also included a validation cohort consisting of 269 patients with colitis-associated mCRC and 29,596 patients with sporadic mCRC.

Patients with microsatellite instability-high mCRC were excluded from the analysis because the researchers wanted to minimize potentially confounding variables related to hereditary cancer and focus specifically on colitis-associated mCRC, Dr Villarreal said.

Link Between Colitis-Associated mCRC and Early-Onset mCRC

The researchers found that colitis-associated mCRC was “strongly associated” with early-onset mCRC, Dr Villarreal said. 

In the discovery cohort, among early-onset mCRC cases, more than twice as many patients had colitis-associated mCRC as had sporadic mCRC (44% and 21%, respectively; odds ratio [OR], 2.9; 95% CI, 1.4-5.8). The same was true in the validation cohort (47% and 18%, respectively; OR, 4.0; 95% CI, 3.2-5.1). 

The researchers also found that signet ring cell and mucinous (SRC/M) histology was associated with colitis-associated mCRC and early-onset mCRC.

In the discovery cohort, SRC/M was found in 38% of colitis-associated mCRC patients and 12% of those with sporadic mCRC (OR, 4.5; 95% CI, 2.2-9.4). In the validation cohort, SRC/M was found in 29% of colitis-associated mCRC patients and 11% of those with sporadic mCRC (OR, 3.1; 95% CI, 2.4-4.1).

In the discovery cohort, SRC/M was found in 16% of early-onset mCRC cases and 12% of late-onset mCRC cases (OR, 1.4; 95% CI, 1.0-1.9). In the validation cohort, SRC/M was found in 14% of patients with early-onset mCRC and 11% of those with late-onset mCRC (OR, 1.3; 95% CI, 1.2-1.4). 

Because SRC/M histology was associated with both colitis-associated mCRC and early-onset mCRC, the researchers proposed that they could use SRC/M as a biomarker for colitis-associated mCRC to estimate the occurrence of undiagnosed IBD in patients with early-onset mCRC. 

The researchers compared the prevalence of SRC/M in early-onset mCRC (13%) and late-onset mCRC (11%) in the validation cohort, assumed that excess cases are related to IBD, and adjusted their estimate to correct for the fact that only a portion of colitis-associated mCRC patients have SRC/M histology (28%).

The researchers performed this analysis in both cohorts and estimated that 9.8% to 10.6% of early-onset mCRC cases may be attributable to undiagnosed IBD. The cancers in these young patients would be expected to have similar tumor biology as colitis-associated mCRC, Dr Villarreal said. 

This article originally appeared on Cancer Therapy Advisor