Although one of the main causes of disease-related death in patients with Crohn disease (CD) is gastrointestinal (GI) cancers, diagnosis strategies and appropriate treatment selection in this patient population currently remains a significant challenge for physicians. A case-by-case analysis in a multidisciplinary approach is often advised, as it has the potential to ensure the best diagnostic and therapeutic evaluations of patients with CD following GI cancer onset. These findings are based on a review published in Cancers.

Study author Claudio Fiorillo and colleagues conducted a review to provide a comprehensive summary of the current knowledge on CD-related GI malignancies. The investigators discovered that in the first decades of the last century, a connection between inflammatory bowel disease (IBD) and colorectal cancer (CRC) was identified. Patients with CD are known to be at an increased risk of developing CRC compared with the general population.

However, a recent meta-analysis and case-control study showed similar overall survival between patients with CD-related CRC and patients with sporadic CRC. More specifically, a study spanning nearly 50 years found a mortality of 0.47/1000 person years (PY) and 0.31/1000 PY for CD-related and sporadic CRC, respectively.


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Small bowel carcinoma (SBC) is a rare complication of CD, with an estimated cumulative risk of 2.2% following a 25-year clinical history of regional ileitis. Patients with CD are also considered to be at an increased risk of developing anal cancer, mainly in the forms of fistula-associated anal carcinoma (carcinoma arising from perianal fistula). In a large case-control study, after prospectively monitoring >2900 patients with a history of active or previous anal/perianal CD, there was an incidence of 0.38/1000 PY and 0.26/1000 PY for adenocarcinoma and squamous cell carcinoma, respectively.

Although endoscopy remains the preferred method of diagnosis and surveillance of GI malignancies, radiologic imaging is becoming an appropriate diagnosis and adequate tumor staging. However, endoscopic surveillance is considered a well-established procedure that can reduce CRC-related mortality by detecting malignant and premalignant lesions (eg, dysplasia).

In a large retrospective study that included 6823 patients with IBD, the subgroup of patients undergoing surveillance colonoscopy had a significantly lower incidence of CRC. In addition, computed tomography and magnetic resonance imaging may be useful in the detection of intestinal cancers in patients with IBD. Overall, the diagnosis of cancer in patients with IBD currently remains a significant challenge for physicians.

Previous studies have shown that the percentage of success in comorbid IBD can be influenced by the choice and/or timing of oncological treatments. However, the study authors noted, “The impact of oncological treatments on IBD has been poorly investigated.”

In a study of 69 patients who began cancer therapy while their IBD was in remission, 17.4% experienced a relapse. Hormonal therapy alone (hazard ratio [HR] 11.04 [95% CI, 1.22-99.85]) or in combination with cytotoxic chemotherapy (HR 9.71 [95% CI, 1.16-81.08]) was linked to an increased risk for IBD reactivation. On the contrary, cytotoxic chemotherapy induced IBD clinical remission in 66.7% of patients who began cancer therapies with active IBD.

The researchers found that colorectal resection with lymphadenectomy was considered the gold standard for treatment of resectable CD-related CRCs. Key factors that should be considered for indication of surgery are disease localization and cancer stage, patient characteristics, comorbidities, expected quality of life, and CD natural history. In addition, the lifetime risk for intestinal resection is 80% for patients with CD. This may increase the complexity of surgical procedures while influencing the surgical treatment choice.

Evidence on the interactions between chemotherapeutic agents and therapies for IBD is currently lacking. However, the use of chemotherapeutic agents for GI cancers combined with IBD therapeutic schemes could result in multiple potentially detrimental effects.

Patients with CRC with IBD were found to experience more treatment delays related to GI toxicity compared with patients without IBD (74% vs 44%; P =.03). The 5-year overall survival in patients with stage IV CRC with IBD was significantly shorter when compared against patients with stage IV CRC without IBD (19% vs 50%; P =.017). The study authors proposed that oncologists should consider the risk/benefit ratio in the treatment choice of patients with IBD and cancer, especially GI cancer.

Artificial intelligence (AI) and machine learning (ML) show promise and represent a step forward in IBD diagnosis and management. The investigators noted that AI can enhance the detection rate of adenoma in the general population, with a sensitivity and specificity of 98% and 93%, respectively. The use of ML may also be beneficial, with its potential to distinguish between different types of polyps (benign or malignant), as well as between inflammatory or neoplastic lesions.

The study authors concluded that adequate assessment of risk factors, ad hoc surveillance, and selecting the most appropriate treatment strategy has the potential to yield more desirable long-term outcomes in patients with CD following GI cancer onset. These findings highlight the importance of a multidisciplinary management approach to mitigating the challenges associated with the diagnosis and treatment of these patients. Though, it should be noted that further large cohort studies in a randomized setting are warranted to ascertain the best diagnostic and treatment pathways.

Reference

Fiorillo C, Schena CA, Quero G, et al. Challenges in Crohn’s disease management after gastrointestinal cancer diagnosis. Cancers. 2021;13(3):574.  doi:10.3390/cancers13030574.