Table 3.

Epidemiology and prevention of CRC in IBDs; key messages divided per topic.

Epidemiology

Epidemiology of sporadic CRC: CRC is the third most frequent form of malignancy and the second in terms of mortality and cancer-related DALYs; its incidence is increasing worldwide.

Epidemiology of IBDs: IBDs’ incidences and costs have been increasing in the last few decades. Clinicians and national health systems will increasingly have to deal with these conditions.

Epidemiology of CRC in patients with IBDs: Risk of IBD-associated CRC is higher in UC than in CD. Thanks to increased adherence to endoscopic surveillance and the improved quality of endoscopy and clinical management, its incidence is now decreasing.

Risk Factors

These can be divided into: Patient-related factors: young age at diagnosis (<20 years), male gender and family history of CRC; Disease-related factors: extension of colitis and its duration (>10 years), concomitant PSC and inflammatory activity.

Primary prevention

5-Aminosalicylic Acid compounds: 5-aminoacylates can be reasonably regarded as chemoprevention tools in association with proper endoscopic surveillance. Therefore, their long-term use should be encouraged.

Thiopurines: Thiopurines’ chemopreventive effects are not supported by strong clinical evidence. Furthermore, non-melanoma skin and lymphopoietic cell cancers are known side effects of their prolonged use.

Anti-TNFα agents: There is not sufficient evidence to support clear protective effects. Further findings are needed to analyze their potential chemopreventive role in patients with IBD. Therefore, international guidelines do not recommend anti-TNFα drugs as chemopreventive agents.

Ursodeoxycholic Acid: The effect of UDCA is debated and controversial. In any case, it should not be used, especially at high doses, as a chemopreventive agent in patients affected by UC and PSC.

Dietary compounds and lifestyle habits: Even if a clear chemopreventive role of a specific diet or lifestyle habit has not been identified yet, some lifestyle strategies already validated for sporadic CRC, such as avoiding smoking and alcohol use and reducing red meat consumption, should be suggested.

Statins: Further studies are needed to confirm the potential role of statins in chemoprevention of IBS-associated CRC.

Vitamin D: Initial studies suggest a chemopreventive role for Vitamin D, but evidence is scarce. Given its high tolerability profile, it should be further investigated.

Gut microbiome composition: Since many alterations in the gut microbiome are involved in IBD pathogenesis, probiotics and prebiotics could have a potential role in the treatment of patients with IBD. Specific studies on their potential role in CRC prevention are needed.

Secondary prevention

Open surveillance issues: Endoscopic surveillance is an important prevention strategy; nevertheless, its effectiveness still needs to be demonstrated by RCTs.

Timing of surveillance: Surveillance colonoscopies should start 8 years after the onset of symptoms, at the time of diagnosis when PSC is present.

Optimal endoscopic technique: Enhanced dysplasia detection techniques (VCE or DCE) with non-targeted biopsies of non-suspicious areas and targeted biopsies of abnormalities should be performed.

Management of dysplasia detection: Grade of confirmed dysplasia (LGD vs. HGD) as well as its visibility and resectability are crucial. Colectomy is necessary in case of unresectable visible dysplasia or HGD or invisible multifocal dysplasia, while endoscopic polypectomy should be chosen if the lesions can be resected.

Tertiary prevention

CRC recurrence in patients with IBDs is rare. Surveillance could be proposed for patients with concomitant PSC or chronic pouchitis.

CRC = colorectal carcinoma; UC = ulcerative colitis; CD = Crohn’s disease; IBDs = inflammatory bowel diseases; TNFα = tumor necrosis Factor α; RCTs = randomized controlled trials; VCE = virtual chromoendoscopy; DCE = dye chromoendoscopy; HGD = high-grade dysplasia; LGD = low-grade dysplasia; PSC = primary sclerosing cholangitis.