The Perioperative Period is an Underutilized Window of Therapeutic Opportunity in Patients With Colorectal Cancer

In Brief Objective: In this review, we address the underlying mechanisms by which surgery augments metastases outgrowth and how these insights can be used to develop perioperative therapeutic strategies for prevention of tumor recurrence. Summary Background Data: Surgical removal of the primary tumor provides the best chance of long-term disease-free survival for patients with colorectal cancer (CRC). Unfortunately, a significant part of CRC patients will develop metastases, even after successful resection of the primary tumor. Paradoxically, it is now becoming clear that surgery itself contributes to development of both local recurrences and distant metastases. Methods: Data for this review were identified by searches of PubMed and references from relevant articles using the search terms “surgery,” “CRC,” and “metastases.” Results: Surgical trauma and concomitant wound-healing processes induce local and systemic changes, including impairment of tissue integrity and production of inflammatory mediators and angiogenic factors. This can lead to immune suppression and enhanced growth or adhesion of tumor cells, all of which increase the chance of exfoliated tumor cells developing into secondary malignancies. Conclusions: Because surgery remains the appropriate and necessary means of treatment for most CRC patients, new adjuvant therapeutic strategies that prevent tumor recurrence after surgery need to be explored since the perioperative therapeutic window of opportunity offers promising means of improving patient outcome but is unfortunately underutilized. Although surgical removal provides the best chance of cure for patients with colorectal cancer, it is becoming clear that surgery also contributes to metastasis. Unfortunately, this notion remains underappreciated. In this review, we describe the mechanisms of surgery-induced metastases outgrowth and address how these insights can be used to develop novel perioperative therapeutic strategies for prevention of tumor recurrence.