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Compared with the general population, individuals with Crohn's disease (CD) are at increased risk of developing and dying of colorectal cancer (CRC), according to the first population-based study of CRC-specific mortality in these patients.

In a combined Danish-Swedish cohort, 499 of 47,035 CD patients in national registers were diagnosed with CRC over a 48-year period, and 296 died of it over a median follow-up of approximately 10 years. "These numbers represent a 40% increased relative risk of CRC diagnosis and a 74% increased relative risk of CRC death in patients with Crohn's disease between 1969-2017," Ola Olén, MD, of the Karolinska Institutet in Stockholm, Sweden, and colleagues wrote.

The results, published online in , showed that CD patients potentially eligible for current surveillance regimens with a disease duration of at least 8 years or primary sclerosing cholangitis had an increased risk of CRC diagnosis and CRC mortality, but the increased risk was restricted to those with CD onset before age 40 who had concurrent primary sclerosing cholangitis or colonic disease.

"These observations should be taken into account when recommending CRC surveillance for patients with Crohn's disease," the team said, noting that age is an overlooked factor in current CRC surveillance guidelines.

In addition, the researchers stated, while CD has long been a reported CRC risk factor, previous studies reflect older treatment and surveillance strategies, and most have assessed risks for incident CRC without taking surveillance and lead-time bias into account.

Study Details

Across both countries the overall mean age of patients and controls was 38 years, and 55% of participants were female. During follow-up, 499 (0.82 per 1,000 person-years) cases of incident CRC were diagnosed in CD patients compared with 4,084 (0.64 per 1000 person-years) cases in age- and sex-matched reference individuals from the general population, corresponding to an overall adjusted hazard ratio (HR) of 1.40 (95% CI 1.27-1.53).

Additionally, 296 (0.47 per 1,000 person-years) CRC deaths occurred in those with CD compared with 1,968 (0.31 per 1000 person-years) in the reference group, corresponding to an overall adjusted HR of 1.74 (1.54-1.96), the researchers reported.

The HR of developing CRC significantly increased in all age groups except older CD patients, who had an HR of 1.13 (95% CI 0.96-1.32). Risk was highest in children with CD: HR 5.90 (95% CI 3.43-10.2).

In another finding, CRC was not diagnosed earlier or at a less severe tumor stage in CD patients than in reference individuals who developed the malignancy, suggesting a surveillance gap, the team explained.

Writing in an accompanying Jason K. Hou, MD, MS, of Baylor College of Medicine in Houston, said the analysis identified the subgroup with the highest HR of CRC mortality -- that is, patients diagnosed with CD before age 40. "However, the highest absolute risk of CRC mortality remains among patients over 60 years of age," he cautioned.

Yet, despite guidelines on colonoscopy surveillance in patients with ulcerative colitis and CD, the rates of even among high-risk groups with ulcerative colitis and primary sclerosing cholangitis have remained disappointingly low, said Hou.

"Healthcare providers need to better communicate risk of CRC to patients with Crohn's disease, and remove barriers to colonoscopy surveillance for patients at risk," he wrote. "Moreover, clinical researchers need to refine their ability to stratify patients most likely to benefit from surveillance resources. To do so, they need more precise means of analyzing the extent of Crohn's disease, and they need to identify optimal colonoscopy surveillance intervals, which are currently still undefined."

Study limitations, Olén and co-authors said, included the largely Caucasian populations of Denmark and Sweden and the countries' universal healthcare coverage, with implications for possibly different associations in other ethnic groups or healthcare systems. In addition, the register-based data did not include information on potential lifestyle risk factors such as low use of non-steroidal anti-inflammatory drugs, low physical activity, high meat consumption, and smoking. There was also no data on endoscopic disease activity, fecal calprotectin concentrations, and clinical measures of disease activity, although the degree and duration of inflammation may be CRC risk factors in inflammatory bowel disease patients.

Also, the team continued, in terms of risk estimates according to disease location, the study relied strictly on registry classifications and could not ascertain which patients should have undergone surveillance based on disease location. Finally, the effect of different types of drugs on CRC risk fell outside the study's scope, and it did not have information on the indications for endoscopy before 2003.