Journal of Cancer Therapy, 2012, 3, 1104-1118 http://dx.doi.org/10.4236/jct.2012.36145 Published Online December 2012 (http://www.SciRP.org/journal/jct) Recent Advances in the Management of Stage IV Colon Cancer Rani Kanthan 1 , Jenna-Lynn Senger 1 , Shahid Ahmed 2 , Selliah Kanthan 3 1 Department of Pathology and Laboratory Medicine, University of Saskatchewan, Saskatoon, Canada; 2 Medical Oncologist, Saska- toon Cancer Centre, Saskatoon, Canada; 3 Department of Surgery, University of Saskatchewan, Saskatoon, Canada. Email: rani.kanthan@saskatoonhealthregion.ca Received October 20 th , 2012; revised November 22 nd , 2012; accepted December 2 nd , 2012 ABSTRACT Colon cancer is the second commonest cause of cancer-related death in Canadian men and women, with approximately one-third of patients dying from this disease. One quarter of patients present with metastases initially, and up to half of all colon cancer patients will develop stage IV disease over the course of their life. Despite ongoing advances in the evolution of newer cytotoxic drugs, targeted biological agents and improved metastasectomy techniques, the gain in overall survival in these patients is of low magnitude. This manuscript is a targeted review of the recent advances over the last decade in the management of advanced stage IV colon cancer as available in the published English literature. The two major arms of metastatic colon cancer management that include surgery and systemic chemotherapy and pal- liative measures as available are discussed. A multi-modality team-based approach involving medical oncologists, sur- gical oncologists, radiologists, and other health-care providers continues to be critical for ongoing success in the thera- peutic management of these patients. Future studies of well-designed prospective, randomized-controlled clinical trials to develop and evaluate newer therapeutic strategies are recommended for continued and improved understanding for optimization of clinical management in advanced colon cancer. Keywords: Stage IV Colon Cancer; Systemic Therapy; Surgical Management 1. Introduction Despite ongoing advancements in screening and early detection such as fecal molecular markers [1], approxi- mately one million new cases of colon cancer continue to be diagnosed annually with 500,000 deaths being directly attributed to the same each year [2]. Amongst these new cases, 19% - 25% present initially with metastatic disease. Additionally, up to 50% of patients with early stage dis- ease will develop metastases during their lifetime [2-4]. Though early stage colon cancer is associated with a 5-year survival rate of 74%, this percentage declines dramatically to 5% - 10% in stage IV disease [5]. Stage IV colon cancer is characterized by metastatic spread to other organs via the blood and the lymphatics. The in- volvement of a single extra-colonic organ is designated as stage IVA and metastases in multiple organs as stage IVB. The most common site of extra-colonic metastases is the liver followed by the lung and the peritoneum. The genetic and epigenetic changes associated with this me- tastatic spread remain poorly understood. Recent ad- vances in molecular studies, however, indicate that mul- tiple markers such as growth factors (prostaglandin E2, epithelial growth factor, and vascular endothelial growth factor) and the epithelial-mesenchymal transition mecha- nisms may be involved [6]. As pharmacological, radiotherapeutic, and surgical fields diversify and progress; management strategies to treat advanced colon cancer are continually evolving. Currently, the majority of patients with stage IV disease are treated with chemotherapy and biological agents; however, no consensus guidelines are universally ac- cepted for the best-practice management of stage IV co- lon cancer. Treatment standardization is additionally hindered by two competing factors: 1) patient population with different expectations and goals, and 2) tumor pro- files with varied chemotherapeutic sensitivity and re- sectability. Although for most patients with advanced colon cancer (CC), the treatment goals are to prolong overall survival (OS) and to maintain quality of life (QOL) for as long as possible, some patients with ad- vanced CC particularly those with limited metastases can be cured following targeted metastasectomy [7,8] (Fig- ure 1). Of note, selected patients with initially unre- sectable disease may become eligible for resection if they achieve a good response to systemic therapy. 75% - 90% of stage IV colon cancers are not suitable for curative Copyright © 2012 SciRes. JCT