Bevacizumab and Postoperative Complications After Hepatic Surgery for Colorectal Metastases

Abstract

TO THE EDITOR: I congratulate Kesmodel et al from The University of Texas M. D. Anderson Cancer Center concerning their recent article in Journal of Clinical Oncology proposing that preoperative bevacizumab does not significantly increase postoperative complications in patients undergoing liver surgery for colorectal cancer metastases. The congratulations are not due to the superiority of their data, but importantly to their self-criticism of the data. The authors concluded that neither the use of bevacizumab nor the timing of bevacizumab administration increases surgical complication rates. However, they qualify their statement by relating that confirmatory prospective studies are required. This is important because in the discussion section of their article, they indeed relate that because their study is retrospective from a single institution with a small number of patients (81 patients in the chemotherapy-plus-bevacizumab group and 44 patients in the chemotherapy-alone group), definitive conclusions about the safety of neoadjuvant bevacizumab and its timing of discontinuation cannot be made. Since the type of chemotherapy, the decision to use bevacizumab, and the duration of chemotherapy and bevacizumab administration, along with the timing of surgical consultation, are at the discretion of the treating physician, the conclusion of their manuscript is preliminary and, as they have stated, must be confirmed prospectively. This group of investigators has a significant experience with hepatic resection of colorectal metastases and continues to recommend waiting at least 6 weeks from discontinuation of bevacizumab before hepatic resection is performed. We certainly can learn from retrospective series, but to the credit of these authors, the self-criticism of their data is laudable. Unfortunately, this is not the case with many retrospective series that appear in the literature, whereupon readers will take the conclusions as definitive. Many of the issues discussed by the authors of this article will be part of the aims of an NCI phase III clinical trial to evaluate neoadjuvant versus adjuvant infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX) plus bevacizumab in patients with potentially resectable hepatic colorectal metastases. The concept of this trial was developed by the Gastrointestinal Leadership of the National Surgical Adjuvant Breast and Bowel Project, American College of Surgeons Oncology Group, and the North Central Cancer Treatment Group. This trial has received approval by the National Cancer Institute Colon Task Force and will soon be presented to the National Cancer Institute Gastrointestinal Steering Committee for discussion. The trial will randomly assign patients with resectable colorectal hepatic metastases to FOLFOX plus bevacizumab before resection followed by the same combination postoperatively versus hepatic resection first followed by postoperative FOLFOX plus bevacizumab. Although the primary end point will be progression-free survival, many secondary end points will be evaluated, including perioperative morbidity related to the agents utilized. I congratulate the authors for discussing the shortcomings of their retrospective review, which should be an example for other authors.