Colitis-associated cancers

Abstract

Patients with inflammatory bowel disease (IBD), both ulcerative colitis and Crohn disease, are at increased risk for cancers of the colon and rectum, as well as cancers of the small bowel in Crohn disease. Long duration of IBD and inflammatory burden are thought to be key risk factors for development of colitis-associated cancer (CAC), though IBD is diagnosed at the same time as cancer in ~10-15% of newly diagnosed CACs. While the incidence of CAC appears to be decreasing over time, likely as a result of improved endoscopic techniques and better medical therapy, the cumulative lifetime risk remains substantial. Particularly among individuals who develop IBD as children or adolescents, CAC remains an important source of long-term morbidity and mortality (Malham et al., Aliment Pharmacol Ther 50:33-39, 2019; El-Matary et al., Front Pediatr 8:400, 2020). Because the symptoms may overlap with those of active inflammatory bowel disease, CACs are frequently diagnosed at an advanced stage, with locally advanced or metastatic disease. The biologic events driving the development of CAC in chronically inflamed bowel are not completely understood, but substantial progress has been made in identifying the difference in genomic alterations between CAC and sporadic colorectal cancer. Clinical and research efforts in CAC have focused primarily on early detection and prevention. Patients with IBD undergo frequent surveillance colonoscopies to promote early detection and removal of precancerous (dysplastic) lesions as well as timely referral for surgery for lesions not amenable to endoscopic resection. This chapter will review the clinical presentation of CAC, recent progress in defining the genomic profile of CAC, epidemiology and risk factors, chemoprevention, and advances in surveillance and endoscopic techniques as well as the treatment of advanced CAC. It will also briefly review other IBD-associated cancers, including small-bowel adenocarcinoma, as well as extra-intestinal cancers that occur in higher frequency among patients with IBD. Finally, it will highlight limitations and research priorities in the area of CAC, which include absence of established non-invasive methods for diagnosis of dysplasia or cancer, limitations to the efficacy of currently available tools for surveillance and early detection, absence of effective methods for surveillance of the small bowel in Crohn Disease, and uncertainties about appropriate endoscopic versus surgical management of colonic neoplasia.