Colorectal Cancer – Management of Metastatic Disease

Oncology & Hematology Review, 2014;10(1):37–41


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 Citation Oncology & Hematology Review, 2014;10(1):37–41
Correspondence: Paul H Sugarbaker, 106 Irving Street, NW, Suite 3900, Washington, DC 20010, US. E:

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

  1. Willet WC, Stampfer MJ, Colditz GA, et al., Relation of meat, fat, and fiber intake to the risk of colon cancer in a progressive study among women, N Engl J Med, 1990;323:1664–72.
  2. Mandel JS, Bond JH, Church TR, et al., Reducing mortality from colorectal cancer by screening for fecal occult blood, N Engl J Med, 1993;328:1365–71.
  3. L ieberman DA, Weiss DG, Bond JH, et al., Use of colonoscopy to screen asymptomatic adults for colorectal cancer, N Engl J Med, 2000;343:162–8.
  4. West NP, Hohenberger W, Weber K, et al., Complete mesocolic excision with central vascular ligation produces an oncologically superior specimen compared with standard surgery for carcinoma of the colon, J Clin Oncol, 2010;28(2):272–8.
  5. Quirke P, Durdey P, Dixon M, Williams N, Local recurrence of rectal adenocarcinoma due to inadequate surgical resection: histopathological study of lateral tumour spread and surgical excision, Lancet, 1986;2:996–9.
  6. Sugarbaker PH, Successful management of microscopic residual disease in large bowel cancer, Cancer Chemother Pharmacol, 1999;43(Suppl.):S15–25.
  7. Sugarbaker PH, Colorectal cancer metastases, a surgical perspective, Surg Oncol Clin N Am, 2013;22(2):289–98.
  8. Swanson RS, Compton CC, Stewart AK, Bland KI, The prognosis of T3N0 colon cancer is dependent on the number of lymph nodes examined, Ann Surg Oncol, 2003;10(1):65–71.
  9. L e Voyer TE, Sigurdson ER, Hanlon AL, et al, Colon cancer survival is associated with increasing number of lymph nodes analyzed: a secondary survey of intergroup trial INT-0089, J Clin Oncol, 2003;21(15):2912–9.
  10. Wilson SM, Adson MA, Surgical treatment of hepatic metastases from colorectal cancers, Arch Surg, 1976;111:330–4.
  11. Foster JH, Berman MM, Solid liver tumors, WB Saunders: Philadelphia, 1977.
  12. H ughes KS, Simon RM, Songhorabodi S, et al., Resection of the liver for colorectal carcinoma metastases: A multi institutional study of indications for resection, Surgery, 1987;103:278–88.
  13. Kaido T, Verification of evidence in surgical treatment for colorectal liver metastases, Hepato-Gastroenterology, 2008;55:378–80.
  14. Fernandez-Trigo V, Shamsa F, Sugarbaker PH, et al., Repeat liver resections from colorectal metastasis, Surgery, 1995;117:296–304.
  15. A dam R, Delvart V, Pascal G, et al., Rescue surgery for unresectable colorectal liver metastases downstaged by chemotherapy: a model to predict long-term survival, Ann Surg, 2004;240:644–57.
  16. Sugarbaker PH, Surgical management of primary and metastatic cancer of the liver, In: Shiff E (Ed.), Diseases of the Liver, JB Lippincott: Philadelphia, 1993:1297–319.
  17. A bdalla EK, Vauthey JN, Ellis LM, et al., Recurrence and outcomes following hepatic resection, radiofrequency ablation, and combined resection/ablation for colorectal liver metastases, Ann Surg, 2004;239(6):818–25.
  18. G roeschl RT, Pilgrim CH, Hanna EM, et al., Microwave ablation for hepatic malignancies: A multidisciplinary analysis, Ann Surg, 2013; [Epub ahead of print]
  19. Joosten J, Jager G, Oyen W, et al., Cryosurgery and radiofrequency ablation for unresectable colorectal liver metastases, Eur J Surg Oncol, 2005;31(10):1152–9.
  20. Solbiati L, Livraghi T, Goldberg SN, et al., Percutaneous radiofrequency ablation of hepatic metastases from colorectal cancer: long-term results in 117 patients, Radiology, 2001;221(1):159–66.
  21. Buell JF, Cherqui D, Geller DA, et al., The international position on laparoscopic liver surgery: The Louisville Statement, 2008, Ann Surg, 2009;250:825–30.
  22. Sugarbaker PH, Jablonski KA, Prognostic features of 51 colorectal and 130 appendiceal cancer patients with peritoneal carcinomatosis treated by cytoreductive surgery and intraperitoneal chemotherapy, Ann Surg, 1995;221(2):124–32.
  23. Shen P, Hawksworth J, Lovato J, et al., Cytoreductive surgery and intraperitoneal hyperthermic chemotherapy with mitomycin C for peritoneal carcinomatosis from nonappendiceal colorectal carcinoma, Ann Surg Oncol, 2004;11(2):178–86.
  24. Verwaal VJ, van Ruth S, Witkamp A, et al., Long-term survival of peritoneal carcinomatosis of colorectal origin, Ann Surg Oncol, 2005;12(1):65–71.
  25. G lehen O, Kwiatkowski F, Sugarbaker PH, et al., Cytoreductive surgery combined with perioperative intraperitoneal chemotherapy for the management of peritoneal carcinomatosis from colorectal cancer: A multi-institutional study, J Clin Oncol, 2004;22(16):3284–92.
  26. Elias D, Gilly F, Boutitie F, et al., Peritoneal colorectal carcinomatosis treated with surgery and perioperative intraperitoneal chemotherapy: Retrospective analysis of 523 patients from a multicentric French study, J Clin Oncol, 2010;28(1):63–8.
  27. Verwaal VJ, Long-term results of cytoreduction and HIPEC followed by systemic chemotherapy, Cancer J, 2009;15:212–5.
  28. Verwaal VJ, van Ruth S, de Bree E, et al., Randomized trial of cytoreduction and hyperthermic intraperitoneal chemotherapy versus systemic chemotherapy and palliative surgery in patients with peritoneal carcinomatosis of colorectal cancer, J Clin Oncol, 2003;21:3737–43.
  29. Verwaal VJ, Bruin S, Boot H, et al., 8-year follow up of a randomized trial: Cytoreduction and hyperthermic intraperitoneal chemotherapy versus systemic chemotherapy in patients with peritoneal carcinomatosis of colorectal cancer, Ann Surg Oncol, 2008;15:2426–32.
  30. Ryan DP, Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: History repeating itself or a new standard?, Am Soc Clin Oncol, 2011.
  31. Franko J, Ibrahim Z, Gusani NJ, et al., Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy versus systemic chemotherapy alone for colorectal peritoneal carcinomatosis, Cancer, 2010;116(16):3756–62.
  32. Sugarbaker PH, Achieving long-term survival with cytoreductive surgery and perioperative chemotherapy to peritoneal surfaces for metastatic colon cancer, Am Soc Clin Oncol, 2011.
  33. Pihl E, Hughes ES, McDermott FT, et al., Lung recurrence after curative surgery for colorectal cancer, Dis Colon Rectum, 1987;30(6):417–9.
  34. Jarabo JR, Fernandez E, Calatayud J, et al., More than one pulmonary resections or combined lung-liver resection in 79 patients with metastatic colorectal carcinoma, J Surg Oncol, 2011;104:781–6.
  35. Welter S, Jacobs J, Krbek T, et al., Long-term survival after repeated resection of pulmonary metastases from colorectal cancer, Ann Thorac Surg, 2007;84(1):203–10.
  36. D e Giacomo T, Rendina EA, Venuta F, et al., Thoracoscopic resection of solitary lung metastases from colorectal cancer is a viable therapeutic option, Chest, 1999;115:1441–3.
  37. King J, Glenn D, Clark W, et al., Percutaneous radiofrequency ablation of pulmonary metastases in patients with colorectal cancer, Br J Surg, 2004;91(2):217–23.
  38. Elias D, Liberale G, Vernerey D, et al., Hepatic and extrahepatic colorectal metastases: When resectable, their localization does not matter, but their total number has a prognostic effect, Ann Surg Oncol, 2005;12(11):900–9.
  39. H eadrick JR, Miller DL, Nagorney DM, et al., Surgical treatment of hepatic and pulmonary metastases from colon cancer, Ann Thorac Surg, 2001;71(3):975–9.
  40. Robinson BJ, Rice TW, Strong SA, et al., Is resection of pulmonary and hepatic metastases warranted in patients with colorectal cancer?, J Thorac Cardiovasc Surg, 1999;117(1):66–75.
  41. Elias D, Sideris L, Pocard M, et al., Results of R0 resection for colorectal liver metastases associated with extrahepatic disease, Ann Surg Oncol, 2004;11(3):274–80.
  42. A ugust DA, Sugarbaker PH, Schneider PD, Lymphatic dissemination of hepatic metastases, Cancer, 1985;55:1490–4.
  43. I watsuki S, Dvorchik I, Madariaga JR, et al., Hepatic resection for metastatic colorectal adenocarcinoma: a proposal of a prognostic scoring system, J Am Coll Surg, 1999;189:291–9.
  44. Eveno C, Goere D, Dartigues P, et al., Ovarian metastasis is associated with retroperitoneal lymph node relapses in women treated for colorectal peritoneal carcinomatosis, Ann Surg Oncol, 2013;20:491–6.
  45. Evers DJ, Verwaal VJ, Indication for oophorectomy during cytoreduction for intraperitoneal metastatic spread of colorectal or appendiceal origin, Br J Surg, 2011;98:287–92.
  46. O kumura S, Kondo H, Tsuboi M, et al., Pulmonary resection for metastatic colorectal cancer: experiences with 159 patients, J Thorac Cardiovasc Surg, 1996;112(4):867–74.
  47. Y edibela S, Klein P, Feuchter K, et al., Surgical management of pulmonary metastases from colorectal cancer in 153 patients, Ann Surg Oncol, 2006;13(11):1538–44.
  48. I noue M, Kotake Y, Nakagawa K, et al., Surgery for pulmonary metastases from colorectal carcinoma, Ann Thorac Surg, 2000;70(2):380–3.
  49. Sauer R, Becker H, Hohenberger W, et al., Preoperative versus postoperative chemoradiotherapy for rectal cancer, N Engl J Med, 2004;351:1731–40.
  50. Verrees JF, Fernandez-Trigo V, Sugarbaker PH, Rectal cancer recurrence after prior resection and radiation therapy: Palliation following additional surgery, Int J Colorectal Dis, 1996;11(5):211–6.
  51. Mukherjee A, Total pelvic exenteration for advanced rectal cancer, S D J Med, 1999;52:153–6.
  52. H addock MG, Nelson H, Donohue JH, et al., Intraoperative electron radiotherapy as a component of salvage therapy for patients with colorectal cancer and advanced nodal metastases, Int J Radiat Oncol Biol Phys, 2003;56:966–73.
  53. Sugarbaker PH, Cytoreductive surgery plus hyperthermic perioperative chemotherapy for selected patients with peritoneal metastases from colorectal cancer: A new standard of care or an experimental approach?, Gastroenterol Res Pract, 2012;13(8):e362–9.
  54. Sugarbaker PH, Second-look surgery for colorectal cancer: Revised selection factors and new treatment options for greater success, Int J Surg Oncol, 2011;2011:915078.
Keywords: Lymph node metastases, liver metastases, peritoneal metastases, peritoneal carcinomatosis, lung metastases, hyperthermic intraperitoneal chemotherapy (HIPEC), early post-operative intraperitoneal chemotherapy (EPIC)