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CRC Metastasis

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Process of Metastasis

Through metastasis, cancer cells can travel from the primary tumor site to distant organs, such as the liver, lungs, and bone. This dynamic process requires an environment in which tumor cells can proliferate, invade surrounding tissues, be released into the circulation, invade a distant organ, establish their own blood supply (angiogenesis), and grow.

Metastasis and Survival

Nearly half of patients with newly diagnosed CRC develop metastases. About 25% of patients present with stage IV (metastatic) disease.1 The median survival for stage IV CRC with standard chemotherapy is approximately 15 months.2 The addition of bevacizumab increases median survival to 20 months.3 Unfortunately, the 5-year survival rate for stage IV CRC is < 5%.2,4

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Figure 1. Liver and peritoneal metastases.

Intra-abdominal seeding model of A, liver, and B, abdominal wall. C, Photomicrograph of HT-29 cell tumor implant of the parietal peritoneum. D, Photomicrograph showing tumor invasion through the liver capsule. (From Scaife et al,8 with permission.)

Liver and peritoneal metastases.

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Sites of CRC Metastasis

CRC tends to metastasize to the liver; among patients with CRC, liver metastases represent the major cause of death. Depending on the stage of the primary tumor at diagnosis, liver metastases may occur in 20% to 70% of patients, and lung metastases in 10% to 20%. Spread to bone is relatively rare, affecting fewer than 2% of CRC patients.5

Mechanism of CRC Metastasis

CRC generally spreads through the lymphatics or portal venous system to the liver.6 Other mechanisms of spread include transperitoneal metastasis (seeding through the serosa) or intraluminal metastasis (seeding into the lumen, as a blood vessel), which is rare (Figure 1).7,8 One theory of metastasis that may account for spread beyond the lymphatic or portal venous system is “seed and soil,” proposed in 1889 by Stephen Paget.9 Paget theorized that cells are carried in all directions in the bloodstream but deposit and grow only if they fall on congenial “soil.” Emerging gene expression microarrays suggest that tumor cells may be programmed early on and that an individual’s cancer already carries a particular prognostic signature.10

Site of Primary CRC and Prognosis

Some investigators have explored the possible link between the location of the primary CRC and the occurrence and site of metastatic disease. Wang et al11 reported that cancer of the right side of the colon correlates significantly with liver recurrence (P = .0071). However, extensive evidence from the Gastrointestinal Tumor Study Group (GITSG) showed that tumor location (left, right, rectosigmoid, or sigmoid) was of low prognostic value.12

Resection of CRC Liver Metastasis: Benefits

A select group of patients with resectable liver metastases may be treated with resection followed by chemotherapy. Resection of CRC liver metastases can give 5-year survival rates between 25% and 40%, although only 7% to 10% of patients with CRC liver metastases ultimately benefit from resection. Best results are seen with a solitary liver lesion.13

Treatment Guidelines for Metastatic CRC

Guidelines for chemotherapy regimens for stage IV CRC are located here; click on the Keeping Current tab. In addition, the National Comprehensive Cancer Network (NCCN) guidelines for treatment of metastatic CRC can be found here.

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References

  1. Nozue M, Oshiro Y, Kurata M, et al. Treatment and prognosis in colorectal cancer patients with bone metastases. Oncol Rep. 2002;9:109-112.
  2. Macdonald JS. Adjuvant therapy of colon cancer. CA Cancer J Clin. 1999;49:202-219.
  3. Hurwitz H, Fehrenbacher L, Novotny W, et al. Bevacizumab plus irinotecan, fluorouracil and leucovorin for metastatic colorectal cancer. N Engl J Med. 2004;350:2335-2342.
  4. Van Cutsem EJ, Kataja VV; ESMO Guidelines Task Force. ESMO Minimum Clinical Recommendations for diagnosis, adjuvant treatment and follow-up of colon cancer. Ann Oncol. 2005;16(suppl 1):i16-i17.
  5. Cunningham D, Findlay M. The chemotherapy of colon cancer can no longer be ignored. Eur J Cancer. 1993;29A:2077–2079.
  6. Hess KR, Varadhachary GR, Taylor SH. Metastatic patterns in adenocarcinoma. Cancer. 2006;106:1624-1633.
  7. Sharma S, Saltz LB, Ota DM, et al. Colon cancer: management of locoregional disease. In: Kelsen DP, Daly JM, Kern DE, et al, eds. Gastrointestinal Oncology: Principles and Practice. Philadelphia, Pa: Lippincott Williams & Wilkins. 2002: 755-780.
  8. Scaife CL, Kuang J, Wills JC, et al. Nuclear factor κB inhibitors induce adhesion-dependent colon apoptosis: implications for metastasis. Cancer Res. 2002;62:6870-6878.
  9. Paget S. The distribution of secondary growths in cancer of the breast. Lancet. 1889;133:571-573.
  10. Van’t Veer LJ, Weigelt B. Road map to metastasis. Nat Med. 2003;9:999-1000.
  11. Wang JY, Chiang JM, Jeng LB, et al. Resection of liver metastases from colorectal cancer: are there any truly significant clinical prognosticators? Dis Colon Rectum. 1996;39:847-851.
  12. Libuth SK, Saltz, LB, Rutgi, AK, et al. Cancer of the colon. In: DeVita VT Jr, Hellman S, SA Rosenberg, eds. Cancer: Principles and Practice of Oncology. 7th ed. Philadelphia, Pa: Lippincott Williams & Wilkins. 2005: 1075.
  13. Goldberg RM, Fleming TR, Tangen CM, et al. Surgery for recurrent colon cancer: strategies for identifying resectable recurrence and success rates after resection. Eastern Cooperative Oncology Group, the North Central Cancer Treatment Group, and the Southwest Oncology Group. Ann Intern Med. 1998;129:27-35.

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