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Colorectal Cancer – Management of Metastatic Disease

Oncology & Hematology Review, 2014;10(1):37–41 DOI: http://doi.org/10.17925/OHR.2014.10.1.37

Abstract:

Metastases from colon cancer occur to the regional lymph nodes, the liver and the peritoneal surfaces. Rectal cancer may disseminate to these sites and also to the lungs. These metastases may occur synchronously with the detection of primary disease or metachronously in follow-up. The timing of the metastatic process is important in terms of treatment possibilities. Each anatomical site for metastatic disease has the potential for an individualised management strategy. Systemic chemotherapy as an adequate management plan for all sites of colorectal metastatic disease is not compatible with a high standard of care. Formulation of an optimal plan combining surgery with regional and systemic chemotherapy is a necessary function of the multidisciplinary team.
Keywords: Lymph node metastases, liver metastases, peritoneal metastases, peritoneal carcinomatosis, lung metastases, hyperthermic intraperitoneal chemotherapy (HIPEC), early post-operative intraperitoneal chemotherapy (EPIC)
Disclosure: The author has no conflicts of interest to declare.
Received: October 17, 2013 Accepted: October 29, 2013
Correspondence: Paul H Sugarbaker, 106 Irving Street, NW, Suite 3900, Washington, DC 20010, US. E: Paul.Sugarbaker@medstar.net

An erratum to this article can be found below.

The management of colorectal cancer has continued to evolve over approximately one century. Without a doubt the most effective management strategy to combat this disease is prevention. This involves the identification of high-risk groups, dietary changes and dietary supplements.1 The next most effective management strategy is screening for disease to confirm a diagnosis of colon or rectal cancer in its early natural history. The use of the haemoccult test on a regular basis has been proven effective.2 Better yet, for screening is complete colonoscopy.3 In symptomatic patients, the surgical management strategies have been well defined for both colon cancer and for rectal cancer. The surgery must provide a complete clearance of the primary cancer and its lymph node groups at risk for metastatic disease. The resection must be accomplished with perfect containment of the process.4,5 A tragic modern-day surgical reality continues in that a patient may enter the operating room with a contained process and leave with disseminated disease. Iatrogenic cancer dissemination results from trauma to the surgical specimen so that cancer cells are not contained and are lost from the specimen into the resection site or free peritoneal cavity.6 The long-term result is local recurrence and peritoneal metastases. This can occur with open colorectal surgery or with laparoscopic resection.

This manuscript is not a commentary on the majority of patients who have an uncomplicated colorectal cancer resection and a favourable prognosis. It concerns the approximately 30 % of patients who have advanced disease at the time of presentation and the 50 % of patients who months or years after resection are found to have progressive disease as a result of treatment failure of primary disease. The focus is on local recurrence and metastases from colon and rectal cancer.7

Lymph Nodal Metastases from Colorectal Cancer
In the past, extensive lymphadenectomy as part of a colorectal cancer resection was thought by many surgeons to be unnecessary. The rationale was that patients with metastases to the intermediate or para-aortic nodes could not survive even if these nodes were resected as part of the primary colorectal cancer surgical intervention. Recent data suggests that this retreat to a ‘conservative resection’ was not indicated. Rather, data now shows that one should perform a wide resection of lymph nodes to the superior mesenteric vessels with a right colon cancer. With a left-sided malignancy, nodes should be resected to the origin of the inferior mesenteric artery.

Swanson and colleagues reported on the survival of 35,787 prospectively collected cases of T3N0 colon cancers that were surgically treated and pathologically reported from 1985–91. T3 cancers would be expected to be at a higher risk for lymph nodal metastases as compared to T1 or T2 lesions and therefore, adequate lymphadenectomy would show a greater benefit in this subgroup of patients. The five-year survival of T3N0M0 colon cancer patients varied from 64 % if one or two lymph nodes were examined to 86 % if greater than 25 lymph nodes were examined. Three strata of resected lymph nodes (1–7, 8–12 and greater than 13) resulted in significantly different five-year survival rates. The authors conclude that the prognosis of T3N0 colon cancer patients is dependent on the number of lymph nodes examined and suggest a minimum of 13 lymph nodes to be resected.8

Le Voyer and colleagues reported on survival from an intergroup trial, INT-0089. In 3,411 assessable patients, 648 had no evidence of lymph node metastases. Multivariate analyses were performed on both the node positive and node negative groups separately to ascertain the effect of extent of lymph node resection on survival. As might be expected, survival decreased with increasing number of lymph nodes involved (p=0.0001). After controlling for the number of nodes involved, survival increased as more nodes were analysed (p=0.0001). Even when no nodes were involved, overall survival and cause-specific survival improved as more nodes were available for analysis (p=0.0005 and p=0.007, respectively). The authors conclude that the number of lymph nodes resected and available for analysis for staging colon cancer is itself a prognostic variable on outcome.9

West and colleagues investigated prognostic implications of the plane of surgical resection of colonic cancer. The complete mesocolic excision with central vascular ligation produced a survival of greater than 89 %. There was a greater yield of lymph nodes in 49 specimens from Erlangen, Germany as compared to 40 standard specimens from Leeds, UK; a lymph node yield of 30 in Erlangen was compared to 18 in Leeds (p<0.0001). West and colleagues conclude that the plane of colon cancer resection and the extent of lymphadenectomy are important in optimal surgical technique. The improved containment of a mesocolic resection combined with the associated larger number of lymph nodes removed was suggested as the explanation for improved survival rates reported in Erlangen.4

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Keywords: Lymph node metastases, liver metastases, peritoneal metastases, peritoneal carcinomatosis, lung metastases, hyperthermic intraperitoneal chemotherapy (HIPEC), early post-operative intraperitoneal chemotherapy (EPIC)
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