Cancer Recurrence After Surgery: A Role for Regional Anesthesia?

Most cancer surgery is performed with curative intent. Despite complete resection to microscopically negative margins, however, cancer deaths subsequent to surgery remain common because of metastatic disease. Investigators have developed and continue to refine a variety of adjuvant and neoadjuvant systemic treatments for cancer patients with the intent of obliterating disseminated disease before it becomes a life-threatening metastatic burden. The importance of these systemic treatments underscores the statistical likelihood that many patients harbor micrometastatic disease at the time of clinical presentation. These tumor cells increase in volume because of seeding at the time of resection or because of an increased growth rate after surgery. In addition, the variety of existing cytotoxic agents and targeted systemic treatments that are currently in use and in development attest to the biologic complexity of metastatic pathways. Cancer dissemination requires release (‘‘shedding’’) of metastatic cells from a primary tumor, cell migration (local, lymphatic, intravascular) to a metastatic site, adherence and/or endothelial migration, angiogenesis, and, most importantly, evasion of host immune surveillance. At each step, there are a myriad of cellular and molecular regulatory processes that may be susceptible to therapeutic intervention. Adjuvant cytotoxic systemic therapy is generally delayedweeks after surgery to facilitate wound healing before the administration of medications, which could lead to immune suppression and increase the risk of postoperative infection. However, there are many studies to show that cellular and molecular events that are critical to the metastatic process may be significantly influenced during and immediately after surgery. Peach et al recently reported that the presence of circulating tumor cells in the blood 24 hours after colon surgery is a negative prognosticator for overall survival. This suggests the perioperative period as a possible window of therapeutic opportunity for eradication of micrometastatic cancer. In addition, events that are a critical part of recovery from major surgery including inflammation, wound healing, and the neuroendocrine (stress) response to major injury may also be involved in determining the likelihood of cancer recurrence after surgery. These observations all suggest that there may be an opportunity to interrupt the metastatic process before initiation of traditional systemic therapy. Although 95% to 97% of women diagnosed with breast cancer have no detectable clinical evidence of distant metastatic disease at the time of presentation, breast cancer remains the second leading cause of cancer death among American women. Women with nodal involvement at the time of presentation have an 83% 5-year survival (http://seer.cancer.gov/statfacts/html/breast.html#survival) with death resulting from the development of distant metastasis. This underscores the resilience of circulating tumor cells that endure despite surgical and systemic therapies. Breast cancer surgery is less physiologically and metabolically disruptive than surgery for intra-abdominal and intrathoracic malignancies. As a consequence, breast cancer may be an ideal target for investigation of interventions that are designed to minimize perioperative perturbations that have been linked to cancer recurrence and metastasis. In this issue of Regional Anesthesia and Pain Medicine, Deegan et al provide an example of how two disparate anesthetic techniques, both with generally accepted clinical response profiles, can manifest significantly different effects on intermediate outcomes that are experimentally associated with cancer recurrence. Most notably, their study addresses the previously demonstrated concepts that the minimization of pain and opiate consumption may decrease the risk of cancer recurrence. In addition, the authors examine the possibility that soluble mediators of the neuroendocrine and/or tissue injury response, both of which are potentially associated with the metastatic process, may be manipulated by anesthetic technique. The authors compared propofol anesthesia combined with a continuous paravertebral block to sevoflurane anesthesia combined with systemic opiate analgesia. The former technique was chosen presumably because of animal evidence that propofol, in comparison to other general anesthetics, does not inhibit natural killer (NK) cell antitumor activity and is associated with fewer experimental lung tumor metastases. In addition, paravertebral EDITORIAL