Bevacizumab-associated fistula formation in postoperative colorectal cancer patients

Background: Adjuvant chemotherapy regimens for metastatic colorectal cancer (CRC) routinely include bevacizumab, a monoclonal antibody targeting vascular endothelial growth factor (VEGF). We have identified a correlation between bevacizumab and fistula formation after resection of advanced CRC. Study Design: Patients undergoing treatment with bevacizumab for metastatic CRC after 2005 were identified and reviewed. Of 222 consecutive patients, 9 patients treated with bevacizumab subsequently developed fistulas. These patients' charts were reviewed with attention to diagnosis, timing of operation relative to bevacizumab therapy, location of fistula, and fistula treatment. Results: Of the 9 identified patients (9 of 222, 4.1%), 6 had rectal cancer, 2 had colon cancer, and 1 had synchronous CRC. Fistulas were most commonly anal or perineal (6 of 9, 66.7%) and colovesicular (3 of 9, 33%). On average, bevacizumab was initiated 23.6 months after the initial operation; complications occurred 3.9 months after starting bevacizumab. Nearly uniformly, cessation of bevacizumab led to fistula healing; however, 3 patients (33%) required fecal diversion. Conclusions: Bevacizumab is the most common antiangiogenesis agent used for treatment of metastatic CRC. Previous adverse events associated with bevacizumab treatment include venous thromboembolism, poor wound healing, and spontaneous bowel perforation. In this report, late postoperative development of fistulas occurred relatively soon after initiation of bevacizumab and usually spontaneously resolved with cessation of bevacizumab treatment. Based on the timing of fistula development relative to operation and initiation of bevacizumab, fistulas are likely secondary to bevacizumab therapy rather than postsurgical complications. Bevacizumab-induced fistulas occur in a small, but significant proportion of CRC patients and must be recognized early.