Surgery for Cancer: A Trigger for Metastases

Abstract

Surgery is a crucial intervention and provides a chance of cure for patients with cancer. The perioperative period is characterized by an increased risk for accelerated growth of micrometastatic disease and increased formation of new metastatic foci. The true impact for cancer patients remains unclear. This review summarizes the often fragmentary clinical and experimental evidence supporting the role of surgery and inflammation as potential triggers for disease recurrence. Surgery induces increased shedding of cancer cells into the circulation, suppresses antitumor immunity allowing circulating cells to survive, upregulates adhesion molecules in target organs, recruits immune cells capable of entrapping tumor cells, and induces changes in the target tissue and in the cancer cells themselves to enhance migration and invasion to establish at the target site. Surgical trauma induces local and systemic inflammatory responses that can also contribute to the accelerated growth of residual and micrometastatic disease. Furthermore, we address the role of perioperative factors, including anesthesia, transfusions, hypothermia, and postoperative complications, as probable deleterious factors contributing to early recurrence. Through the admittedly limited understanding of these processes, we will attempt to provide suggestions for potential new therapeutic approaches to target the protumorigenic perioperative window and ultimately improve long-term oncological outcomes. Cancer Res; 77(7); 1548-52. ©2017 AACR.

Figure 1

Effects of tumor removal on promotion of metastases. These effects include accelerated growth of micrometastases and establishment of new metastatic foci. Surgery increases tumor cell dissemination, increased circulating tumor cells’ survival by enhancing immune evasion, enhanced entrapment at metastatic site and increased invasion and migration capabilities to establish new metastatic foci. Surgery can also induce changes in the environment of micrometastatic disease to enhance its growth. Multiple therapeutic approaches illustrated in this diagram can be considered to target the protumorigenic inflammatory changes in the perioperative period.