The Evolving Care of Metastatic Colorectal Cancer

July 11, 2011

Progress in the care of mCRC has occurred relatively rapidly, but current methods of management have placed a significant economic burden on the healthcare system.

Colorectal cancer (CRC) accounts for 9% of all cancer diagnoses and 9% of all cancer-related deaths in the United States.[1] Over the past 15 years, CRC incidence in the US has declined by about 2% per year.[2] A number of factors have been reported to be associated with this downward trend. These include regular physical activity, a variety of dietary factors, regular use of aspirin or nonsteroidal anti-inflammatory drugs, and use of hormone replacement therapy by postmenopausal women.[3,4] Death rates from CRC have also been on the decline in the US, since the mid 1980s. This improvement in outcome can be attributed in part to detection and removal of colonic polyps, detection of CRCs at an earlier stage, and the availability of more effective treatments, particularly adjuvant therapy. Over the past 12 years, significant progress has been made in the treatment of CRC, with US Food and Drug Administration approval of six new therapeutic agents that are active in patients with this malignancy.[5]

Despite these encouraging trends, however, more than 50% of patients who present with localized disease will eventually develop metastatic disease. The liver is the most common initial site of disease spread, but metastases to other organs during the course of the disease are common, and include the lungs, peritoneum, and intra-abdominal lymph nodes.[5] Patients with a small number of isolated metastases may be cured of their disease by surgical resection.[6] The decisions regarding metastasectomy are made by the interdisciplinary team, including a medical oncologist; an experienced surgeon; interventional radiologists; and, in some cases, a radiation oncologist.

CRC patients with metastasis to the liver, the most common site of metastatic disease for this malignancy, can present a management challenge. The article by Gail Wilkes in this issue of ONCOLOGY Nurse Edition clearly presents the challenges faced by the interdisciplinary team in caring for patients with CRC metastatic to the liver, in terms of treatment options for patients who are clearly resectable, potentially resectable, who may be eligible for re-resection after disease recurrence, or who may require systemic chemotherapy and biotherapy for widely metastatic disease. Also discussed are the utilization and clinical implications of biomarkers, specifically KRAS and BRAF mutations, as molecular determinants of response to treatment of CRC.

For patients with mCRC who have isolated liver metastases, regional approaches can be considered, as opposed to systemic therapy. These include surgical resection, local tumor ablation, cryotherapy, radiofrequency ablation, regional hepatic intra-arterial chemotherapy, and chemoembolization. Among these options, surgery is the only treatment associated with a survival advantage.

Advances in surgical techniques and systemic chemotherapy have challenged the traditional criteria for liver resection eligibility. Hepatic resection was once reserved for patients who had no more than three hepatic lesions in the same lobe, the possibility of achieving a 1-cm margin, and no portal lymph node invasion; advances in care have made liver resection possible for many more patients, however, and these old rules no longer apply.[7] Most clinicians take an aggressive approach toward management of liver metastases, because improvements in mCRC patient outcomes over the past 15 years can be attributed to increased use of liver resection in selected patients.[8] Neoadjuvant chemotherapy has the potential to convert some patients who have initially unresectable disease (either because of large lesions or liver metastases at a critical location) to resectable status. Nevertheless, the optimal selection criteria, specific regimen, duration of therapy, and how it should be incorporated in the care of these patients have not been defined.[9]

Most patients with mCRC are candidates for systemic chemotherapy to palliate symptoms and prolong life. Available data in 2011 support the use of a fluoropyrimidine, irinotecan (Camptosar), oxaliplatin (Eloxatin), bevacizumab (Avastin), and either cetuximab (Erbitux) or panitumumab (Vectibix) in the treatment of patients with mCRC. The optimal sequence of these agents remains under investigation, although patients who receive all the agents have an improved survival. Over the past 15 years, mortality has decreased by 13% in patients with mCRC.[1] This decrease in mortality highlights the interdisciplinary approach to care for patients with mCRC, bringing together gastroenterologists, oncologists, surgeons, primary care providers, pathologists, and nurses. While this progress has occurred relatively rapidly, the current methods of managing mCRC, and use of newer therapeutic agents in particular, have placed a significant economic burden on the healthcare system.[10,11] In the future, healthcare providers and society may be faced with difficult decisions regarding resource allocation and innovative cancer treatments, given that the current trajectory of clinical progress in the setting of mCRC is likely to be maintained.[11]

Financial Disclosure:The author has no significant financial interest or other relationship with the manufacturers of any products or providers of any service mentioned in this article.



1. American Cancer Society. Cancer Facts and Figures. Atlanta, GA, American Cancer Society, 2011. Available at Accessed on June 20, 2011.

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4. Wolin KY, Yan Y, Colditz GA, et al: Physical activity and colon cancer prevention: A metaanalysis. Brit J Cancer 100(4):611–616, 2009.

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6. Tomlinson JS, Jarnagin WR, DeMatteo RP, et al: Actual 10-year survival after resection of colorectal liver metastases defines cure. J Clin Oncol 25(29):4575–4580, 2007.

7. Khatri S, Petrilli NJ, Belghiti J: Extending the frontiers of surgical therapy for hepatic colorectal metastases: Is there a limit? J Clin Oncol 23(33):8490–8499, 2005.

8. Kopetz, S, Chang GJ, Overman MJ, et al: Improved survival in metastatic colorectal cancer is associated with adoption of hepatic resection and improved chemotherapy. J Clin Oncol 27(22):3677–3683, 2009.

9. Reddy SK, Zorzi D, Lum YW, et al: Timing of multimodality therapy for resectable synchronous colorectal liver metastases: A retrospective multi-institutional analysis. Ann Surg Oncol 16(7):1809–1819, 2009.

10. Schrag D: The price tag on progress-chemotherapy for colorectal cancer. N Engl J Med 351(4):317–319, 2004.

11. Meropol NJ, Schulman KA: Cost of cancer care: Issues and implications. J Clin Oncol 25(2):180–186, 2007.