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

Abstract

Background & Aims Carcinoma associated with perianal fistula in Crohn’s disease is a pending threat for patients. This study was 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 forty patients with proven malignancy associated with perianal Crohn’s fistulas and forty randomly-selected controls with fistulizing perianal Crohn’s disease. Differences between groups were analysed and multivariate calculations 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 to fistula had a diagnosis of Crohn’s disease in 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 both groups. Signs for complicated and severe fistulation including complex anatomy and chronic activity occurred significantly more often in patients with malignancy associated to fistula. Significant multivariate hazard ratios for overall mortality and progression-free survival were shown for histologic type of cancer, metastatic disease and R1 resection. Overall survival (OS) 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 risk for 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.

Cancer in Anal Fistulas

“…Palmieri et al demonstrated via multicenter retrospective analysis that SCC is associated with lower overall survival when compared with adenocarcinoma. 16 Additionally, they identified positive nodal status, distant metastases, and inability to achieve R0 resection as predictors of poor prognosis. As expected, advanced stage at the time of diagnosis (T3-T4) was also recognized as an indicator of low survival.…”

“…19 Palmieri and colleagues report a 65% survival rate at 5 years, though this analysis includes all types of FAAC and is not specific to adenocarcinoma. 16 However, a study by Gaertner and colleagues has shown improved survival with aggressive management including aggressive neoadjuvant and adjuvant chemotherapies in addition to APR for patients with advanced disease. Neoadjuvant therapies in this group consisted of 45 to 60 Gy of external beam radiation with one 6-week cycle of 5-fluorouracil (5-FU) and leucovorin.…”

“…Palmieri and colleagues recognized that patients with FAAC have significantly more complex perianal disease compared with CD patients with benign disease. 16 Warning signs that increase suspicion for malignancy in CD patients with perianal disease include acute change in the quality, as well as the severity of pain associated with a chronic fistula. 22 Ultimately, many authors have agreed that any significant worsening of symptoms or change in baseline in patients with chronic, longstanding fistulas warrants deeper investigation.…”

Management of Perianal Crohn's Disease

“…Fecal incontinence is reported in 59% of patients with CD-PAF contributing to a negative health-related quality of life (6,7). Chronic perianal fistulas (PAF) also carry a small risk of malignancy, either squamous cell or adenocarcinoma, within the fistula tract (8). Despite advances in medical therapies, on average, two-thirds of patients with CD-PAF require perianal surgery and approximately 7% require a major abdominal surgery (4).…”

Malignancy rates in Crohn's disease patients with perianal fistula: A German retrospective cohort study

“…However, medical therapies such as thiopurine immunomodulators, anti‐tumor necrosis factor (anti‐TNF), and other biologics for CD have also been linked to the development of cancer. Patients with CD and perianal fistulas (CPF) have been reported to be at a higher risk of skin cancer and lymphoma 2,11–17 . Furthermore, patients with CPF have a greater severity of inflammation compared with patients with non‐PF CD, and given the increased risk of cancer associated with chronic inflammation it is reasonable to expect an elevation in site‐specific cancers in the CPF population compared with the non‐PF population 18,19 .…”