Surgery-induced tumor growth in (metastatic) colorectal cancer

Metastatic colorectal cancer (mCRC) is a devastating disease causing 700.000 deaths annually worldwide. Metastases most frequently develop in the liver. Partial hepatectomy has dramatically improved clinical outcome and is the only curative treatment option for eligible patients with mCRC. Pre-clinical studies have shown that surgical procedures can have tumor-promoting local 'side-effects' such as hypoxia and inflammation, thereby altering the behaviour of residual tumor cells. In addition, systemically released factors following (colon or liver) surgery can act as a wakeup-call for dormant tumor cells in distant organs and/or help establish a pre-metastatic niche. Tumor handling during resection may also increase the number of circulating tumor cells. Despite the overwhelming amount of pre-clinical data demonstrating the pro-tumorigenic side effects of surgery, clinical evidence is scarce. Indications for hepatic surgery are rapidly increasing due to a rise in the incidence of mCRC and a trend towards more aggressive surgical treatment. Therefore, it is increasingly important to understand the principles of surgery-induced tumor growth, in order to devise perioperative or adjuvant strategies to further enhance long-term tumor control. In the current study we review the evidence for surgery-stimulated tumor growth and suggest strategies to assess the clinical relevance of such findings.