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Colorectal Cancer in Ulcerative Colitis and Crohn’s Disease

Findings from a Scandinavian population-based cohort study
17 Feb 2020
Epidemiology/Etiology/Cancer Prevention;  Gastrointestinal cancers

According to a Scandinavian population-based cohort study, individuals with ulcerative colitis (UC) are at increased risk of developing colorectal cancer (CRC) compared with those without UC, are diagnosed with less advanced CRC, and are at increased risk of dying from CRC, although these excess risks have declined substantially over time.

Furthermore, patients with Crohn's disease are at increased risk of diagnosis and death from CRC. Patients with Crohn's disease who have CRC have a higher mortality than patients without Crohn's disease who are also diagnosed with CRC. CRC surveillance should likely be focused on patients diagnosed with Crohn's disease before the age of 40 years, on patients with colon inflammation, and on those who have primary sclerosing cholangitis (PSC).

Colorectal cancer in ulcerative colitis

The authors wrote in background of the study published on 11 January 2020 in The Lancet that UC is a risk factor for CRC. However, available studies reflect older treatment and surveillance paradigms, and most have assessed risks for incident CRC without taking surveillance and lead-time bias into account, such as by assessing CRC incidence by tumour stage, or stage-adjusted mortality from CRC.

The investigators led by Dr Ola Olén of the Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet in Stockholm, Sweden aimed to compare both overall and country-specific risks of CRC mortality and incident CRC among patients with UC. In the population-based cohort study of 96447 patients with UC (of those 32919 in Denmark and 63528 in Sweden), patients were followed-up for CRC incidence and CRC mortality between January 1969 and December 2017, and compared with matched reference 949207 individuals from the general population.

Patients with UC were selected from national registers and included in the analysis if they had two or more records with a relevant International Classification of Disease in the patient register or one such record plus a colorectal biopsy report with a morphology code suggestive of inflammatory bowel disease. For every patient with UC, the study team selected matched reference individuals from the total population registers of Denmark and Sweden, who were matched for sex, age, birth year, and place of residence. They used Cox regression to compute hazard ratios (HRs) for incident CRC, and for CRC mortality, taking tumour stage into account.

During follow-up, the researchers observed 1336 incident CRCs in the UC cohort (1.29 per 1000 person-years) and 9544 incident CRCs in reference individuals (0.82 per 1000 person-years; HR 1.66, 95% confidence interval [CI] 1.57-1.76).

In the UC cohort, 639 patients died from CRC (0.55 per 1000 person-years), compared with 4451 reference individuals (0.38 per 1000 person-years; HR 1.59, 95% CI 1.46-1.72) during the same time period.

The CRC stage distribution in patients with UC was less advanced (p < 0.0001) than in matched reference individuals, but taking tumour stage into account, patients with UC and CRC remained at increased risk of CRC death (HR 1.54, 95% CI 1.33-1.78). The excess risks declined over calendar periods: during the last 5 years of follow-up (2013-2017, Sweden only), the HR for incident CRC in patients with UC was 1.38 (95% CI 1.20-1.60, or one additional case per 1058 patients with UC per 5 years) and the HR for death from CRC was 1.25 (95% CI 1.03-1.51, or one additional case per 3041 patients with UC per 5 years).

The authors concluded that there still seems to be room for improvement in international surveillance guidelines.

The study was funded by the Swedish Medical Society, Karolinska Institutet, Stockholm County Council, Swedish Research Council, Swedish Foundation for Strategic Research, Independent Research Fund Denmark, Forte Foundation and Swedish Cancer Foundation.

Colorectal cancer in Crohn’s disease

In terms of Crohn's disease as a risk factor for CRC, available studies reflect older treatment and surveillance strategies, and most have assessed risks for incident CRC without taking surveillance and lead-time bias into account. Such biases can be accounted for by assessing CRC incidence by tumour stage and CRC mortality by tumour stage. It prompted a same group of investigators to assess rates of incident CRC and CRC mortality among patients with Crohn's disease compared with the general population. They published their findings on 14 February 2020 in The Lancet Gastroenterology & Hepatology.

For this nationwide register-based cohort study, the study team used International Classification of Disease codes in national patient registers and pathology reports to identify incident cases of Crohn's disease. In Denmark they searched for incident cases between January 1977 and December 2011, and in Sweden between January 1969 and December 2017.

For each patient with Crohn's disease, the researchers identified up to ten reference individuals in national population registers and matched them by sex, age, calendar year, and place of residence. Matched reference individuals had to be alive and free of inflammatory bowel disease at the start of follow-up of index patients with Crohn's disease, and stopped contributing to reference person-years if they were diagnosed with inflammatory bowel disease.

The main outcome was death from CRC as main or contributory cause of death captured in the cause-of-death registers. The secondary outcome was incident CRC, as defined by the cancer registers.

The investigators used Cox regression to estimate hazard ratios (HRs) for incident CRC and CRC mortality, taking tumour stage into account. They used a series of Cox models to estimate cause-specific HRs of the different competing outcomes, CRC diagnosis, CRC death, and other causes of death and adjusted for tumour stage at CRC diagnosis.

During the 1969–2017 study period, the study team identified 47035 patients with incident Crohn's disease, of those 13056 in Denmark and 33979 in Sweden, as well as 463187 matched reference individuals.

During follow-up, 296 (0.47 per 1000 person-years) CRC deaths occurred among individuals with Crohn's disease compared with 1968 (0.31 per 1000 person-years) in reference individuals, corresponding to an overall adjusted HR of 1.74 (1.54–1.96).

In total 499 (0.82 per 1000 person-years) cases of incident CRC were diagnosed in patients with Crohn's disease compared with 4084 (0.64 per 1000 person-years) cases in reference individuals, corresponding to an overall adjusted HR of 1.40 (95% CI 1.27–1.53).

Patients with Crohn's disease who were diagnosed with CRC were at increased risk of CRC mortality compared with reference individuals also diagnosed with CRC (HR 1.42 [1.16–1.75] when adjusted for tumour stage), and tumour stage at CRC diagnosis did not differ between groups (p = 0.27).

Patients with Crohn's disease who had follow-up of 8 years or longer or who were diagnosed with PSC and hence were potentially eligible for CRC surveillance had an increased overall risk of CRC death (HR 1.40 [1.16–1.68]) or CRC diagnosis (HR 1.12 [0.98–1.28]). However, in patients potentially eligible for CRC surveillance the study team only found significantly increased risks in patients diagnosed with Crohn's disease before the age of 40 years, patients with disease activity in the colon only, or patients with PSC.

The authors concluded that CRC surveillance should likely be focused on patients diagnosed with Crohn's disease before the age of 40 years, on patients with colon inflammation, and on those who have PSC.

The study was funded by the Swedish Medical Society, Karolinska Institutet, Regional Agreement on Medical Training and Clinical Research between Stockholm County Council and Karolinska Institutet (ALF), Forte Foundation, Swedish Cancer Foundation, and Independent Research Fund Denmark.

 

References

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