QS124 - Anal Squamous Cell Cancer and Precursor Lesions in Patients with IBD – a Propensity Score Matched-Cohort Analysis

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Purpose/Background: Anal squamous cell cancer (aSCC) is a rare disease usually treated with chemoradiation (CRT) following the (modified) Nigro protocol and surveillance depending on the treatment response. Local excision can be considered an alternative to CRT for early stages as a combined diagnostic and therapeutic approach, while major resections are optional for locally advanced stages, persistent, or recurrent cancer. ASCC is associated with multiple risk factors such as smoking, female sex, and immunosuppression. Patients with inflammatory bowel disease (IBD) are at higher risk of developing malignancies. This study aimed to analyze therapeutic approaches, short- and long-term oncological outcomes associated with IBD and identify risk factors.

Methods/Interventions: Retrospectively, patients with IBD and aSCC were identified between 2003 and 2023. The exclusion criteria were histopathological entities other than aSCC, locations other than the anal canal or anal margin, unknown tumor stage, or unverified SCC or IBD diagnosis. The aSCC patients with IBD (study group) were propensity score-matched to a control group at a 1:4 ratio. The matching criteria were age at diagnosis of aSCC, sex, smoking status, and clinical tumor stage (AJCC 8th edition). Statistical analyses of the treatment, treatment response, and short-term outcomes were performed. Overall, disease-free and aSCC-related survival rates were analyzed using Cox proportional hazard regression.

Results/Outcomes: In total, 24 patients were identified having aSCC and IBD, either ulcerative colitis (62.5%) or Crohn’s disease (37.5%) and matched to 96 control patients with anal SCC. The majority of patients were women (54.2%). HIV (16.7% vs. 11.5%, p= 0.50) and HPV (41.7% vs. 33.3%, p= 0.49) infections were similar in both groups. Significantly more patients with IBD had clinical stage 4 disease (p= 0.03). Local excision was similarly part of the initial approach in both groups (29.2% vs. 27.1%, p= 0.09). A total of 8.3% of IBD patients and 11.5% of the control group underwent surveillance afterwards, while (modified) Nigro protocol was applied in 20.8% to IBD patients and in 15.6% to the control group (p= 0.94). (Modified) Nigro protocol with surveillance was the initial therapeutic approach in 29.2% of IBD patients and in 51.0% of the control group (p= 0.75). IBD patients showed a lower rate of complete response to treatment compared to the control group (54.2% vs. 74.0%, p= 0.08), yet without reaching significance. Abdominoperineal resection or exenteration (APR/E) was necessary in 12.5% of patients with IBD and in 21.9% of the control group (p= 0.40) due to incomplete response or recurrence. Dietary, social, work, and sexual restrictions did not differ between groups (p= 0.41, p= 0.20, p= 0.44, and p= 0.13, respectively). Five-year overall survival was significantly lower for IBD patients (HR 2.47, CI 1.28 – 4.77, p= 0.01) and associated with age over 65 years (p= 0.04) and incomplete response (p < 0.01) (Figure 1). Patients with IBD had a shorter disease-free survival (HR 1.02, CI 0.35 – 2.967, p= 0.97) and lower aSCC specific survival (HR 1.96, CI 0.76 – 5.03, p= 0.16).

Conclusion/Discussion: IBD is associated with worse overall survival and reduced response to systemic treatment in those patients who develop aSCC. Therefore, appropriate surveillance and preventive screening for aSCC in IBD patients is essential. However, it remains unclear whether a modified, more aggressive systemic treatment or earlier surgical intervention would be beneficial.