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.
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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.
