Perianal Fistula-Associated Carcinoma in Crohn's Disease: A Multicentre Retrospective Case Control Study

Background and Aims: Carcinoma associated with perianal fistula in Crohn's disease is a pending threat for patients. This study aimed to improve understanding and facilitate development of diagnostic and therapeutic strategies. Methods: A retrospective case-control study was conducted at four German hospitals. The analysis included 40 patients with proven malignancy associated with perianal Crohn's fistulas and 40 randomly selected controls with fistulizing perianal Crohn's disease. Differences between groups were analysed and multivariate calculations were performed to describe risk factors for oncological outcomes. Results: Histology revealed adenocarcinoma in 33/40 patients and squamous cell carcinoma in 7/40 patients. Compared to fistula patients without carcinoma, patients with malignancies associated with fistula had a diagnosis of Crohn's disease at younger age. Crohn's disease lasted longer in patients with malignancy [25.8 9.0 vs 19.6 +/- 10.4; p = 0.006]. Fistula-related findings differed significantly between the two groups. Signs of complicated and severe fistulation including complex anatomy and chronic activity occurred significantly more often in patients with malignancy associated with fistula. Significant multivariate hazard ratios for overall mortality and progression-free survival were shown for histological type of cancer, metastatic disease and R1 resection. Overall survival was 45.1 +/- 28.6 months and the 5-year survival rate was 65%. Conclusions: In patients with adenocarcinoma or squamous cell carcinoma associated with perianal fistula in Crohn's disease, fistula characteristics determine the risk of malignancy. Early diagnosis influences outcomes, while treatment of chronic fistula activity may be key to preventing malignancy. Expert multimodal therapy is paramount for successful treatment of perianal fistula-associated malignancies.