NCI medNews

Treatment statement for Health professionals


Colon Cancer Treatment (PDQ®)

Get this document via a secure connection


General Information About Colon Cancer
Cellular Classification of Colon Cancer
Stage Information for Colon Cancer
Treatment Option Overview for Colon Cancer
Stage 0 Colon Cancer Treatment
Stage I Colon Cancer Treatment
Stage II Colon Cancer Treatment
Stage III Colon Cancer Treatment
Stage IV and Recurrent Colon Cancer Treatment
Changes to This Summary (06/05/2014)
About This PDQ Summary
Get More Information From NCI

General Information About Colon Cancer

Cancer of the colon is a highly treatable and often curable disease when localized to the bowel. Surgery is the primary form of treatment and results in cure in approximately 50% of the patients. Recurrence following surgery is a major problem and is often the ultimate cause of death.

Incidence and Mortality

Note: Estimated new cases and deaths from colon cancer in the United States in 2014: [1]

Gastrointestinal stromal tumors can occur in the colon. (Refer to the PDQ summary on Gastrointestinal Stromal Tumors Treatment for more information.)

Anatomy

Gastrointestinal (digestive) system anatomy; shows esophagus, liver, stomach, colon, small intestine, rectum, and anus.Anatomy of the lower gastrointestinal system.

Risk Factors

Groups that have a high incidence of colorectal cancer include those with hereditary conditions. Together, these groups account for 10% to 15% of colorectal cancers. These groups include the following:

More common conditions with an increased risk include the following:

These high-risk groups account for only 23% of all colorectal cancers. Limiting screening or early cancer detection to only these high-risk groups would miss the majority of colorectal cancers. [6] (Refer to the PDQ summaries on Colorectal Cancer Screening and Colorectal Cancer Prevention for more information.)

Screening

Because of the frequency of the disease, ability to identify high-risk groups, slow growth of primary lesions, better survival of patients with early-stage lesions, and relative simplicity and accuracy of screening tests, screening for colon cancer should be a part of routine care for all adults aged 50 years and older, especially for those with first-degree relatives with colorectal cancer. (Refer to the PDQ summary on Colorectal Cancer Screening for more information.)

Prognostic Factors

The prognosis of patients with colon cancer is clearly related to the following:

These three characteristics form the basis for all staging systems developed for this disease.

Other prognostic factors include the following:

Many other prognostic markers have been evaluated retrospectively for patients with colon cancer, though most, including allelic loss of chromosome 18q or thymidylate synthase expression, have not been prospectively validated. [9] [10] [11] [12] [13] [14] [15] [16] [17] [18] Microsatellite instability, also associated with HNPCC, has been associated with improved survival independent of tumor stage in a population-based series of 607 patients younger than 50 years with colorectal cancer. [19] Patients with HNPCC reportedly have better prognoses in stage-stratified survival analysis than patients with sporadic colorectal cancer, but the retrospective nature of the studies and possibility of selection factors make this observation difficult to interpret. [20]

Treatment decisions depend on factors such as physician and patient preferences and the stage of the disease, rather than the age of the patient. [21] [22] [23]

Racial differences in overall survival (OS) after adjuvant therapy have been observed, without differences in disease-free survival, suggesting that comorbid conditions play a role in survival outcome in different patient populations. [24]

Follow-up and Survivorship

Limited data and no level 1 evidence are available to guide patients and physicians about surveillance and management of patients after surgical resection and adjuvant therapy. The American Society of Clinical Oncology and the National Comprehensive Cancer Network recommend specific surveillance and follow-up strategies. [25] [26]

Following treatment of colon cancer, periodic evaluations may lead to the earlier identification and management of recurrent disease. [27] [28] [29] [30] The impact of such monitoring on overall mortality of patients with recurrent colon cancer, however, is limited by the relatively small proportion of patients in whom localized, potentially curable metastases are found. To date, no large-scale randomized trials have documented an OS benefit for standard, postoperative monitoring program. [31] [32] [33] [34] [35]

CEA is a serum glycoprotein frequently used in the management of patients with colon cancer. A review of the use of this tumor marker suggests the following: [36]

The optimal regimen and frequency of follow-up examinations are not well defined because the impact on patient survival is not clear and the quality of data is poor. [33] [34] [35]

Factors Associated with Recurrence

Diet and exercise

No prospective randomized trials have demonstrated an improvement in outcome with a specific diet or exercise regimen; however, cohort studies suggest that diet or exercise regimen may improve outcome. The cohort studies contain multiple opportunities for unintended bias, and caution is needed when using the data from them.

Two prospective observational studies were performed with patients enrolled on CALGB-89803 (NCT00003835), which was an adjuvant chemotherapy trial for patients with stage III colon cancer. [37] [38] In this trial, patients in the lowest quintile of the Western dietary pattern compared with the highest quintile experienced an adjusted hazard ratio (HR) for disease-free survival of 3.25 (95% confidence interval [CI], 2.04–5.19; P < .001) and an OS of 2.32 (95% CI, 1.36–3.96; P < .001). Additionally, findings included that stage III colon cancer patients in the highest quintile of dietary glycemic load experienced an adjusted HR for OS of 1.76 (95% CI, 1.22–2.54, P < .001) compared with those in the lowest quintile. Subsequently, in the Cancer Prevention Study II Nutrition Cohort, among 2,315 participants diagnosed with colorectal cancer, the degree of red and processed meat intake before diagnosis was associated with a higher risk of death (relative risk [RR], 1.29; 95% CI, 1.05–1.59; P = .03), but red meat consumption after diagnosis was not associated with overall mortality. [39][Level of evidence: 3iiA]

A meta-analysis of seven prospective cohort studies evaluating physical activity before and after a diagnosis of colorectal cancer demonstrated that patients who participated in any amount of physical activity before diagnosis had a RR of 0.75 (95% CI, 0.65–0.87; P < .001) for colorectal cancer-specific mortality compared with patients who did not participate in any physical activity. [40] Patients who participated in a high amount of physical activity (vs. a low amount) before diagnosis had a RR of 0.70 (95% CI, 0.56–0.87; P = .002). Patients who participated in any physical activity (compared with no activity) after diagnosis had a RR of 0.74 (95% CI, 0.58–0.95; P = .02) for colorectal cancer-specific mortality. Those who participated in a high amount of physical activity (vs. a low amount) after diagnosis had a RR of 0.65 (95% CI, 0.47–0.92; P = .01). [40][Level of evidence: 3iiB]

Aspirin

A prospective cohort study examined the use of aspirin after a colorectal cancer diagnosis. [41] Regular users of aspirin after a diagnosis of colorectal cancer experienced an HR of colon cancer-specific survival of 0.71 (95% CI, 0.65–0.97) and an OS of 0.79 (95% CI, 0.65–0.97). [41][Level of evidence: 3iiA] One study evaluated 964 patients with rectal or colon cancer from the Nurse’s Health Study and the Health Professional Follow-up Study. [42] Among patients with PI3K-mutant colorectal cancer, regular use of aspirin was associated with an HR for OS of 0.54 (95% CI, 0.31–0.94; P = .01) [42][Level of evidence: 3iiiA]

Related Summaries

Other PDQ summaries containing information related to colon cancer include the following:

References:

  1. American Cancer Society: Cancer Facts and Figures 2014. Atlanta, Ga: American Cancer Society, 2014. Available online. Last accessed May 21, 2014.
  2. Thorson AG, Knezetic JA, Lynch HT: A century of progress in hereditary nonpolyposis colorectal cancer (Lynch syndrome). Dis Colon Rectum 42 (1): 1-9, 1999.
  3. Smith RA, von Eschenbach AC, Wender R, et al.: American Cancer Society guidelines for the early detection of cancer: update of early detection guidelines for prostate, colorectal, and endometrial cancers. Also: update 2001--testing for early lung cancer detection. CA Cancer J Clin 51 (1): 38-75; quiz 77-80, 2001 Jan-Feb.
  4. Ransohoff DF, Lang CA: Screening for colorectal cancer. N Engl J Med 325 (1): 37-41, 1991.
  5. Fuchs CS, Giovannucci EL, Colditz GA, et al.: A prospective study of family history and the risk of colorectal cancer. N Engl J Med 331 (25): 1669-74, 1994.
  6. Winawer SJ: Screening for colorectal cancer. Cancer: Principles and Practice of Oncology Updates 2(1): 1-16, 1987.
  7. Steinberg SM, Barkin JS, Kaplan RS, et al.: Prognostic indicators of colon tumors. The Gastrointestinal Tumor Study Group experience. Cancer 57 (9): 1866-70, 1986.
  8. Filella X, Molina R, Grau JJ, et al.: Prognostic value of CA 19.9 levels in colorectal cancer. Ann Surg 216 (1): 55-9, 1992.
  9. McLeod HL, Murray GI: Tumour markers of prognosis in colorectal cancer. Br J Cancer 79 (2): 191-203, 1999.
  10. Jen J, Kim H, Piantadosi S, et al.: Allelic loss of chromosome 18q and prognosis in colorectal cancer. N Engl J Med 331 (4): 213-21, 1994.
  11. Lanza G, Matteuzzi M, Gafá R, et al.: Chromosome 18q allelic loss and prognosis in stage II and III colon cancer. Int J Cancer 79 (4): 390-5, 1998.
  12. Griffin MR, Bergstralh EJ, Coffey RJ, et al.: Predictors of survival after curative resection of carcinoma of the colon and rectum. Cancer 60 (9): 2318-24, 1987.
  13. Johnston PG, Fisher ER, Rockette HE, et al.: The role of thymidylate synthase expression in prognosis and outcome of adjuvant chemotherapy in patients with rectal cancer. J Clin Oncol 12 (12): 2640-7, 1994.
  14. Shibata D, Reale MA, Lavin P, et al.: The DCC protein and prognosis in colorectal cancer. N Engl J Med 335 (23): 1727-32, 1996.
  15. Bauer KD, Lincoln ST, Vera-Roman JM, et al.: Prognostic implications of proliferative activity and DNA aneuploidy in colonic adenocarcinomas. Lab Invest 57 (3): 329-35, 1987.
  16. Bauer KD, Bagwell CB, Giaretti W, et al.: Consensus review of the clinical utility of DNA flow cytometry in colorectal cancer. Cytometry 14 (5): 486-91, 1993.
  17. Sun XF, Carstensen JM, Zhang H, et al.: Prognostic significance of cytoplasmic p53 oncoprotein in colorectal adenocarcinoma. Lancet 340 (8832): 1369-73, 1992.
  18. Roth JA: p53 prognostication: paradigm or paradox? Clin Cancer Res 5 (11): 3345, 1999.
  19. Gryfe R, Kim H, Hsieh ET, et al.: Tumor microsatellite instability and clinical outcome in young patients with colorectal cancer. N Engl J Med 342 (2): 69-77, 2000.
  20. Watson P, Lin KM, Rodriguez-Bigas MA, et al.: Colorectal carcinoma survival among hereditary nonpolyposis colorectal carcinoma family members. Cancer 83 (2): 259-66, 1998.
  21. Iwashyna TJ, Lamont EB: Effectiveness of adjuvant fluorouracil in clinical practice: a population-based cohort study of elderly patients with stage III colon cancer. J Clin Oncol 20 (19): 3992-8, 2002.
  22. Chiara S, Nobile MT, Vincenti M, et al.: Advanced colorectal cancer in the elderly: results of consecutive trials with 5-fluorouracil-based chemotherapy. Cancer Chemother Pharmacol 42 (4): 336-40, 1998.
  23. Popescu RA, Norman A, Ross PJ, et al.: Adjuvant or palliative chemotherapy for colorectal cancer in patients 70 years or older. J Clin Oncol 17 (8): 2412-8, 1999.
  24. Dignam JJ, Colangelo L, Tian W, et al.: Outcomes among African-Americans and Caucasians in colon cancer adjuvant therapy trials: findings from the National Surgical Adjuvant Breast and Bowel Project. J Natl Cancer Inst 91 (22): 1933-40, 1999.
  25. Meyerhardt JA, Mangu PB, Flynn PJ, et al.: Follow-up care, surveillance protocol, and secondary prevention measures for survivors of colorectal cancer: American Society of Clinical Oncology clinical practice guideline endorsement. J Clin Oncol 31 (35): 4465-70, 2013.
  26. Benson AB 3rd, Bekaii-Saab T, Chan E, et al.: Localized colon cancer, version 3.2013: featured updates to the NCCN Guidelines. J Natl Compr Canc Netw 11 (5): 519-28, 2013.
  27. Martin EW Jr, Minton JP, Carey LC: CEA-directed second-look surgery in the asymptomatic patient after primary resection of colorectal carcinoma. Ann Surg 202 (3): 310-7, 1985.
  28. Bruinvels DJ, Stiggelbout AM, Kievit J, et al.: Follow-up of patients with colorectal cancer. A meta-analysis. Ann Surg 219 (2): 174-82, 1994.
  29. Lautenbach E, Forde KA, Neugut AI: Benefits of colonoscopic surveillance after curative resection of colorectal cancer. Ann Surg 220 (2): 206-11, 1994.
  30. Khoury DA, Opelka FG, Beck DE, et al.: Colon surveillance after colorectal cancer surgery. Dis Colon Rectum 39 (3): 252-6, 1996.
  31. Safi F, Link KH, Beger HG: Is follow-up of colorectal cancer patients worthwhile? Dis Colon Rectum 36 (7): 636-43; discussion 643-4, 1993.
  32. Moertel CG, Fleming TR, Macdonald JS, et al.: An evaluation of the carcinoembryonic antigen (CEA) test for monitoring patients with resected colon cancer. JAMA 270 (8): 943-7, 1993.
  33. Rosen M, Chan L, Beart RW Jr, et al.: Follow-up of colorectal cancer: a meta-analysis. Dis Colon Rectum 41 (9): 1116-26, 1998.
  34. Desch CE, Benson AB 3rd, Smith TJ, et al.: Recommended colorectal cancer surveillance guidelines by the American Society of Clinical Oncology. J Clin Oncol 17 (4): 1312, 1999.
  35. Benson AB 3rd, Desch CE, Flynn PJ, et al.: 2000 update of American Society of Clinical Oncology colorectal cancer surveillance guidelines. J Clin Oncol 18 (20): 3586-8, 2000.
  36. Clinical practice guidelines for the use of tumor markers in breast and colorectal cancer. Adopted on May 17, 1996 by the American Society of Clinical Oncology. J Clin Oncol 14 (10): 2843-77, 1996.
  37. Meyerhardt JA, Niedzwiecki D, Hollis D, et al.: Association of dietary patterns with cancer recurrence and survival in patients with stage III colon cancer. JAMA 298 (7): 754-64, 2007.
  38. Meyerhardt JA, Sato K, Niedzwiecki D, et al.: Dietary glycemic load and cancer recurrence and survival in patients with stage III colon cancer: findings from CALGB 89803. J Natl Cancer Inst 104 (22): 1702-11, 2012.
  39. McCullough ML, Gapstur SM, Shah R, et al.: Association between red and processed meat intake and mortality among colorectal cancer survivors. J Clin Oncol 31 (22): 2773-82, 2013.
  40. Je Y, Jeon JY, Giovannucci EL, et al.: Association between physical activity and mortality in colorectal cancer: a meta-analysis of prospective cohort studies. Int J Cancer 133 (8): 1905-13, 2013.
  41. Chan AT, Ogino S, Fuchs CS: Aspirin use and survival after diagnosis of colorectal cancer. JAMA 302 (6): 649-58, 2009.
  42. Liao X, Lochhead P, Nishihara R, et al.: Aspirin use, tumor PIK3CA mutation, and colorectal-cancer survival. N Engl J Med 367 (17): 1596-606, 2012.

Cellular Classification of Colon Cancer

Histologic types of colon cancer include the following:

References:

  1. Saclarides TJ, Szeluga D, Staren ED: Neuroendocrine cancers of the colon and rectum. Results of a ten-year experience. Dis Colon Rectum 37 (7): 635-42, 1994.

Stage Information for Colon Cancer

Treatment decisions should be made with reference to the TNM classification [1] rather than to the older Dukes or the Modified Astler-Coller classification schema.

The American Joint Committee on Cancer (AJCC) and a National Cancer Institute–sponsored panel recommended that at least 12 lymph nodes be examined in patients with colon and rectal cancer to confirm the absence of nodal involvement by tumor. [2] [3] [4] This recommendation takes into consideration that the number of lymph nodes examined is a reflection of the aggressiveness of lymphovascular mesenteric dissection at the time of surgical resection and the pathologic identification of nodes in the specimen. Retrospective studies demonstrated that the number of lymph nodes examined in colon and rectal surgery may be associated with patient outcome. [5] [6] [7] [8]

AJCC Stage Groupings and TNM Definitions

The AJCC has designated staging by TNM classification to define colon cancer. [1] The same classification is used for both clinical and pathologic staging. [1]

Table 1. Definitions of TNM Stage 0

StageTNMa,bDukescMACdDescription Illustration
0 Tis, N0, M0Tis = Carcinoma in situ: intraepithelial or invasion of lamina propria.e

Stage 0 colon/rectal carcinoma in situ; shows a cross-section of the colon/rectum. An inset shows the layers of the colon/rectum wall with abnormal cells in the mucosa layer. Also shown are the submucosa, muscle layers, serosa, a blood vessel, and lymph nodes.

N0 = No regional lymph node metastasis.     
M0 = No distant metastasis.     
T = primary tumor; N = regional lymph nodes; M = distant metastasis.
Reprinted with permission from AJCC: Colon and rectum. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 143-164.
The explanations for superscripts a–g are at the end of Table 5.

Table 2. Definitions of TNM Stage I

StageTNMa,bDukescMACdDescriptionIllustration
IT1, N0, M0AAT1 = Tumor invades submucosa.

Stage I colorectal cancer; shows a cross-section of the colon/rectum. An inset shows the layers of the colon/rectum wall with cancer in the mucosa, submucosa, and muscle layers. Also shown are the serosa, a blood vessel, and lymph nodes.

T2 = Tumor invades muscularis propria.     
N0 = No regional lymph node metastasis.     
T2, N0, M0AB1M0 = No distant metastasis.  
T = primary tumor; N = regional lymph nodes; M = distant metastasis.
Reprinted with permission from AJCC: Colon and rectum. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 143-164.
The explanations for superscripts a–g are at the end of Table 5.

Table 3. Definitions of TNM Stage II

StageTNMa,bDukescMACdDescriptionIllustration
IIAT3, N0, M0BB2T3 = Tumor invades through the muscularis propria into pericolorectal tissues.

Stage II colorectal cancer; shows a cross-section of the colon/rectum and a three-panel inset. Each panel shows the layers of the colon/rectum wall: mucosa, submucosa, muscle layers, and serosa. Also shown are a blood vessel and lymph nodes. First panel shows stage IIA with cancer in the mucosa, submucosa, muscle layers, and serosa. Second panel shows stage IIB with cancer in all layers and spreading through the serosa. Third panel shows stage IIC with cancer spreading to nearby organs.

N0 = No regional lymph node metastasis.     
M0 = No distant metastasis.     
IIBT4a, N0, M0 BB2T4a = Tumor penetrates to the surface of the visceral peritoneum.f 
N0 = No regional lymph node metastasis.     
M0 = No distant metastasis.     
IICT4b, N0, M0 BB3T4b = Tumor directly invades or is adherent to other organs or structures.f,g 
N0 = No regional lymph node metastasis.     
M0 = No distant metastasis.     
T = primary tumor; N = regional lymph nodes; M = distant metastasis.
Reprinted with permission from AJCC: Colon and rectum. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 143-164.
The explanations for superscripts a–g are at the end of Table 5.

Table 4. Definitions of TNM Stage III

StageTNMa,bDukescMACdDescriptionIllustration
IIIAT1–T2, N1/N1c, M0CC1T1 = Tumor invades submucosa.

Stage IIIA colorectal cancer; shows a cross-section of the colon/rectum and a two-panel inset. Each panel shows the layers of the colon/rectum wall: mucosa, submucosa, muscle layers, and serosa. Also shown are a blood vessel and lymph nodes. First panel shows cancer in the mucosa, submucosa, muscle layers, and 2 lymph nodes. Second panel  shows cancer in the mucosa, submucosa, and 5 lymph nodes.

T2 = Tumor invades muscularis propria.     
N1 = Metastases in 1–3 regional lymph nodes.     
T1, N2a, M0CC1N1c = Tumor deposit(s) in the subserosa, mesentery, or nonperitonealized pericolic or perirectal tissues without regional nodal metastasis.  
N2a = Metastases in 4–6 regional lymph nodes.     
M0 = No distant metastasis.     
IIIBT3–T4a, N1/N1c, M0CC2T1 = Tumor invades submucosa.

Stage IIIB colorectal cancer; shows a cross-section of the colon/rectum and a two-panel inset. Each panel shows the layers of the colon/rectum wall: mucosa, submucosa, muscle layers, and serosa. Also shown are a blood vessel and lymph nodes. First panel shows cancer in all layers, spreading through the serosa, and in 3 lymph nodes. Second panel shows cancer in all layers and in 5 lymph nodes. Third panel shows cancer in the mucosa, submucosa, muscle layers, and 7 lymph nodes.

T2 = Tumor invades muscularis propria.     
T3 = Tumor invades through the muscularis propria into pericolorectal tissues.     
T4a = Tumor penetrates to the surface of the visceral peritoneum.f     
N1 = Metastases in 1–3 regional lymph nodes.     
N1c = Tumor deposit(s) in the subserosa, mesentery, or nonperitonealized pericolic or perirectal tissues without regional nodal metastasis.     
T2–T3, N2a, M0CC1/C2N2a = Metastases in 4–6 regional lymph nodes.  
N2b = Metastases in ≥7 regional lymph nodes.     
T1–T2, N2b, M0CC1M0 = No distant metastasis.  
IIICT4a, N2a, M0CC2T3 = Tumor invades through the muscularis propria into pericolorectal tissues.

Stage IIIC colorectal cancer; shows a cross-section of the colon/rectum wall and a three-panel inset. Each panel shows the layers of the colon/rectum wall: mucosa, submucosa, muscle layers, and serosa. Also shown are a blood vessel and lymph nodes. First panel shows cancer in all layers, spreading through the serosa, and in 4 lymph nodes. Second panel shows cancer in all layers and in 7 lymph nodes. Third panel shows cancer in all layers, spreading through the serosa, in 2 lymph nodes, and spreading to nearby organs.

T4a = Tumor penetrates to the surface of the visceral peritoneum.f     
T4b = Tumor directly invades or is adherent to other organs or structures.f,g     
T3–T4a, N2b, M0CC2N1 = Metastases in 1–3 regional lymph nodes.  
N2 = Metastases in ≥4 regional lymph nodes.     
N2a = Metastases in 4–6 regional lymph nodes.     
T4b, N1–N2, M0CC3N2b = Metastases in ≥7 regional lymph nodes.  
M0 = No distant metastasis.     
T = primary tumor; N = regional lymph nodes; M = distant metastasis.
Reprinted with permission from AJCC: Colon and rectum. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 143-164.
The explanations for superscripts a–g are at the end of Table 5.

Table 5. Definitions of TNM Stage IV

StageTNMa,bDukescMACdDescriptionIllustration
IVAAny T, Any N, M1aTX = Primary tumor cannot be assessed.

Stage IV colon cancer; shows other parts of the body where colon cancer may spread, including lymph nodes, lung, liver, abdominal wall, and ovary. Inset shows cancer spreading through the blood and lymph nodes to other parts of the body.

T0 = No evidence of primary tumor.     
Tis = Carcinoma in situ: intraepithelial or invasion of lamina propria.e     
T1 = Tumor invades submucosa.     
T2 = Tumor invades muscularis propria.     
T3 = Tumor invades through the muscularis propria into pericolorectal tissues.     
T4a = Tumor penetrates to the surface of the visceral peritoneum.f     
T4b = Tumor directly invades or is adherent to other organs or structures.f,g     
NX = Regional lymph nodes cannot be assessed.     
N0 = No regional lymph node metastasis.     
N1 = Metastases in 1–3 regional lymph nodes.     
N1a = Metastasis in 1 regional lymph node.     
N1b = Metastases in 2–3 regional lymph nodes.     
N1c = Tumor deposit(s) in the subserosa, mesentery, or nonperitonealized pericolic or perirectal tissues without regional nodal metastasis.     
N2 = Metastases in ≥4 regional lymph nodes.     
N2a = Metastases in 4–6 regional lymph nodes.     
N2b = Metastases in ≥7 regional lymph nodes.     
M1a = Metastasis confined to 1 organ or site (e.g., liver, lung, ovary, nonregional node).     
IVBAny T, Any N, M1bTX = Primary tumor cannot be assessed. 
T0 = No evidence of primary tumor.     
Tis = Carcinoma in situ: intraepithelial or invasion of lamina propria.e     
T1 = Tumor invades submucosa.     
T2 = Tumor invades muscularis propria.     
T3 = Tumor invades through the muscularis propria into pericolorectal tissues.     
T4a = Tumor penetrates to the surface of the visceral peritoneum.f     
T4b = Tumor directly invades or is adherent to other organs or structures.f,g     
NX = Regional lymph nodes cannot be assessed.     
N0 = No regional lymph node metastasis.     
N1 = Metastases in 1–3 regional lymph nodes.     
N1a = Metastasis in 1 regional lymph node.     
N1b = Metastases in 2–3 regional lymph nodes.     
N1c = Tumor deposit(s) in the subserosa, mesentery, or nonperitonealized pericolic or perirectal tissues without regional nodal metastasis.     
N2 = Metastases in ≥4 regional lymph nodes.     
N2a = Metastases in 4–6 regional lymph nodes.     
N2b = Metastases in ≥7 regional lymph nodes.     
M1b = Metastases in >1 organ/site or the peritoneum.     
T = primary tumor; N = regional lymph nodes; M = distant metastasis.
Reprinted with permission from AJCC: Colon and rectum. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 143-164.
acTNM is the clinical classification, and pTNM is the pathologic classification. The y prefix is used for those cancers that are classified after neoadjuvant pretreatment (e.g., ypTNM). Patients who have a complete pathologic response (ypT0, N0, cM0) may be similar to stage group 0 or I. The r prefix is to be used for those cancers that have recurred after a disease-free interval (rTNM).
bA satellite peritumoral nodule in the pericolorectal adipose tissue of a primary carcinoma without histologic evidence of residual lymph node in the nodule may represent discontinuous spread, venous invasion with extravascular spread (V1/2), or a totally replaced lymph node (N1/2). Replaced nodes should be counted separately as positive nodes in the N category, whereas discontinuous spread or venous invasion should be classified and counted in the site-specific factor category Tumor Deposits.
cDukes B is a composite of better (T3, N0, M0) and worse (T4, N0, M0) prognostic groups, as is Dukes C (any T, N1, M0 and any T, N2, M0).
dMAC is the modified Astler-Coller classification.
eTis includes cancer cells confined within the glandular basement membrane (intraepithelial) or mucosal lamina propria (intramucosal) with no extension through the muscularis mucosae into the submucosa.
fDirect invasion in T4 includes invasion of other organs or other segments of the colorectum as a result of direct extension through the serosa, as confirmed on microscopic examination (e.g., invasion of the sigmoid colon by a carcinoma of the cecum) or, for cancers in a retroperitoneal or subperitoneal location, direct invasion of other organs or structures by virtue of extension beyond the muscularis propria (i.e., respectively, a tumor on the posterior wall of the descending colon invading the left kidney or lateral abdominal wall; or a mid or distal rectal cancer with invasion of prostate, seminal vesicles, cervix, or vagina).
gTumor that is adherent to other organs or structures, grossly, is classified cT4b. However, if no tumor is present in the adhesion, microscopically, the classification should be pT1–4a depending on the anatomical depth of wall invasion. The V and L classifications should be used to identify the presence or absence of vascular or lymphatic invasion whereas the PN site-specific factor should be used for perineural invasion.

References:

  1. Colon and rectum. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 143-64.
  2. Colon and rectum. In: American Joint Committee on Cancer: AJCC Cancer Staging Manual. 6th ed. New York, NY: Springer, 2002, pp 113-124.
  3. Compton CC, Greene FL: The staging of colorectal cancer: 2004 and beyond. CA Cancer J Clin 54 (6): 295-308, 2004 Nov-Dec.
  4. Nelson H, Petrelli N, Carlin A, et al.: Guidelines 2000 for colon and rectal cancer surgery. J Natl Cancer Inst 93 (8): 583-96, 2001.
  5. Swanson RS, Compton CC, Stewart AK, et al.: The prognosis of T3N0 colon cancer is dependent on the number of lymph nodes examined. Ann Surg Oncol 10 (1): 65-71, 2003 Jan-Feb.
  6. Le 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 21 (15): 2912-9, 2003.
  7. Prandi M, Lionetto R, Bini A, et al.: Prognostic evaluation of stage B colon cancer patients is improved by an adequate lymphadenectomy: results of a secondary analysis of a large scale adjuvant trial. Ann Surg 235 (4): 458-63, 2002.
  8. Tepper JE, O'Connell MJ, Niedzwiecki D, et al.: Impact of number of nodes retrieved on outcome in patients with rectal cancer. J Clin Oncol 19 (1): 157-63, 2001.

Treatment Option Overview for Colon Cancer

Table 6. Standard Treatment Options for Stages 0–III Colon Cancer

Stage (TNM Staging Criteria)Standard Treatment Options
Stage 0 Colon CancerSurgery
Stage I Colon CancerSurgery
Stage II Colon CancerSurgery
Stage III Colon CancerSurgery
Adjuvant chemotherapy 

Table 7. Treatment Options for Stage IV and Recurrent Colon Cancer

Stage (TNM Staging Criteria)Treatment Options
Treatment of Liver MetastasisSurgery
Neoadjuvant chemotherapy 
Local ablation 
Adjuvant chemotherapy 
Intra-arterial chemotherapy 
Treatment of Stage IV and Recurrent Colon Cancer Surgery
Chemotherapy and targeted therapy 

Primary Surgical Therapy

Standard treatment for patients with colon cancer has been open surgical resection of the primary and regional lymph nodes for localized disease.

The role of laparoscopic techniques [1] [2] [3] [4] in the treatment of colon cancer has been examined in two studies.

Evidence (laparoscopic techniques):

  1. A multicenter, prospective, randomized, noninferiority trial (NCCTG-934653) compared laparoscopic-assisted colectomy (LAC) with open colectomy in 872 patients.

  2. One small, single-institution randomized study of 219 patients showed that the LAC procedure was independently associated with reduced tumor recurrence on multivariate analysis. [7][Level of evidence: 1iiB]

Surgery is curative in 25% to 40% of highly selected patients who develop resectable metastases in the liver and lung. Improved surgical techniques and advances in preoperative imaging have allowed for better patient selection for resection.

Adjuvant Chemotherapy

The potential value of adjuvant chemotherapy for patients with stage II colon cancer is controversial. Pooled analyses and meta-analyses have suggested a 2% to 4% improvement in OS for patients treated with adjuvant fluorouracil (5-FU)–based therapy compared with observation. [8] [9] [10] (Refer to the Stage II Colon Cancer Treatment section of this summary for more information.)

Prior to 2000, 5-FU was the only useful cytotoxic chemotherapy in the adjuvant setting for patients with stage III colon cancer. Since 2000, capecitabine has been established as an equivalent alternative to 5-FU and leucovorin. The addition of oxaliplatin to 5-FU and leucovorin has been shown to improve OS compared with 5-FU and leucovorin alone. (Refer to the Stage III Colon Cancer Treatment section of this summary for more information.)

Adjuvant Radiation Therapy

While combined modality therapy with chemotherapy and radiation therapy has a significant role in the management of patients with rectal cancer (below the peritoneal reflection), the role of adjuvant radiation therapy for patients with colon cancer (above the peritoneal reflection) is not well defined. Patterns-of-care analyses and single-institution retrospective reviews suggest a role for radiation therapy in certain high-risk subsets of colon cancer patients (e.g., T4, tumor location in immobile sites, local perforation, obstruction, and residual disease postresection). [11] [12] [13] [14] [15] [16]

Evidence (adjuvant radiation therapy):

  1. Such observations led to the development of a phase III randomized intergroup study designed to test the benefit of adding radiation therapy to surgery and chemotherapy with 5-FU-levamisole for selected high-risk colon cancer patients (e.g., T4; or T3, N1–N2 ascending and/or descending colon). [17]

Adjuvant radiation therapy has no current standard role in the management of patients with colon cancer following curative resection, although it may have a role for patients with residual disease.

References:

  1. Bokey EL, Moore JW, Chapuis PH, et al.: Morbidity and mortality following laparoscopic-assisted right hemicolectomy for cancer. Dis Colon Rectum 39 (10 Suppl): S24-8, 1996.
  2. Franklin ME Jr, Rosenthal D, Abrego-Medina D, et al.: Prospective comparison of open vs. laparoscopic colon surgery for carcinoma. Five-year results. Dis Colon Rectum 39 (10 Suppl): S35-46, 1996.
  3. Fleshman JW, Nelson H, Peters WR, et al.: Early results of laparoscopic surgery for colorectal cancer. Retrospective analysis of 372 patients treated by Clinical Outcomes of Surgical Therapy (COST) Study Group. Dis Colon Rectum 39 (10 Suppl): S53-8, 1996.
  4. Schwenk W, Böhm B, Müller JM: Postoperative pain and fatigue after laparoscopic or conventional colorectal resections. A prospective randomized trial. Surg Endosc 12 (9): 1131-6, 1998.
  5. Clinical Outcomes of Surgical Therapy Study Group: A comparison of laparoscopically assisted and open colectomy for colon cancer. N Engl J Med 350 (20): 2050-9, 2004.
  6. Weeks JC, Nelson H, Gelber S, et al.: Short-term quality-of-life outcomes following laparoscopic-assisted colectomy vs open colectomy for colon cancer: a randomized trial. JAMA 287 (3): 321-8, 2002.
  7. Lacy AM, García-Valdecasas JC, Delgado S, et al.: Laparoscopy-assisted colectomy versus open colectomy for treatment of non-metastatic colon cancer: a randomised trial. Lancet 359 (9325): 2224-9, 2002.
  8. Efficacy of adjuvant fluorouracil and folinic acid in B2 colon cancer. International Multicentre Pooled Analysis of B2 Colon Cancer Trials (IMPACT B2) Investigators. J Clin Oncol 17 (5): 1356-63, 1999.
  9. Gill S, Loprinzi CL, Sargent DJ, et al.: Pooled analysis of fluorouracil-based adjuvant therapy for stage II and III colon cancer: who benefits and by how much? J Clin Oncol 22 (10): 1797-806, 2004.
  10. Mamounas E, Wieand S, Wolmark N, et al.: Comparative efficacy of adjuvant chemotherapy in patients with Dukes' B versus Dukes' C colon cancer: results from four National Surgical Adjuvant Breast and Bowel Project adjuvant studies (C-01, C-02, C-03, and C-04) J Clin Oncol 17 (5): 1349-55, 1999.
  11. Willett C, Tepper JE, Cohen A, et al.: Local failure following curative resection of colonic adenocarcinoma. Int J Radiat Oncol Biol Phys 10 (5): 645-51, 1984.
  12. Willett C, Tepper JE, Cohen A, et al.: Obstructive and perforative colonic carcinoma: patterns of failure. J Clin Oncol 3 (3): 379-84, 1985.
  13. Gunderson LL, Sosin H, Levitt S: Extrapelvic colon--areas of failure in a reoperation series: implications for adjuvant therapy. Int J Radiat Oncol Biol Phys 11 (4): 731-41, 1985.
  14. Willett CG, Fung CY, Kaufman DS, et al.: Postoperative radiation therapy for high-risk colon carcinoma. J Clin Oncol 11 (6): 1112-7, 1993.
  15. Willett CG, Goldberg S, Shellito PC, et al.: Does postoperative irradiation play a role in the adjuvant therapy of stage T4 colon cancer? Cancer J Sci Am 5 (4): 242-7, 1999 Jul-Aug.
  16. Schild SE, Gunderson LL, Haddock MG, et al.: The treatment of locally advanced colon cancer. Int J Radiat Oncol Biol Phys 37 (1): 51-8, 1997.
  17. Martenson JA Jr, Willett CG, Sargent DJ, et al.: Phase III study of adjuvant chemotherapy and radiation therapy compared with chemotherapy alone in the surgical adjuvant treatment of colon cancer: results of intergroup protocol 0130. J Clin Oncol 22 (16): 3277-83, 2004.

Stage 0 Colon Cancer Treatment

Stage 0 colon cancer is the most superficial of all the lesions and is limited to the mucosa without invasion of the lamina propria. Because of its superficial nature, the surgical procedure may be limited.

Standard Treatment Options for Stage 0 Colon Cancer

Surgery

Standard treatment options for stage 0 colon cancer include the following:

  1. Local excision or simple polypectomy with clear margins.
  2. Colon resection for larger lesions not amenable to local excision.

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage 0 colon cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

Stage I Colon Cancer Treatment

Because of its localized nature, stage I colon cancer has a high cure rate.

Standard Treatment Options for Stage I Colon Cancer

Surgery

Standard treatment options for stage I colon cancer include the following:

  1. Wide surgical resection and anastomosis.

Evidence (laparoscopic techniques):

The role of laparoscopic techniques [1] [2] [3] [4] in the treatment of colon cancer was examined in a multicenter, prospective, randomized trial (NCCTG-934653, now closed) comparing laparoscopic-assisted colectomy (LAC) with open colectomy.

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage I colon cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References:

  1. Bokey EL, Moore JW, Chapuis PH, et al.: Morbidity and mortality following laparoscopic-assisted right hemicolectomy for cancer. Dis Colon Rectum 39 (10 Suppl): S24-8, 1996.
  2. Franklin ME Jr, Rosenthal D, Abrego-Medina D, et al.: Prospective comparison of open vs. laparoscopic colon surgery for carcinoma. Five-year results. Dis Colon Rectum 39 (10 Suppl): S35-46, 1996.
  3. Fleshman JW, Nelson H, Peters WR, et al.: Early results of laparoscopic surgery for colorectal cancer. Retrospective analysis of 372 patients treated by Clinical Outcomes of Surgical Therapy (COST) Study Group. Dis Colon Rectum 39 (10 Suppl): S53-8, 1996.
  4. Schwenk W, Böhm B, Müller JM: Postoperative pain and fatigue after laparoscopic or conventional colorectal resections. A prospective randomized trial. Surg Endosc 12 (9): 1131-6, 1998.
  5. Weeks JC, Nelson H, Gelber S, et al.: Short-term quality-of-life outcomes following laparoscopic-assisted colectomy vs open colectomy for colon cancer: a randomized trial. JAMA 287 (3): 321-8, 2002.

Stage II Colon Cancer Treatment

Standard Treatment Options for Stage II Colon Cancer

Surgery

Standard treatment options for stage II colon cancer include the following:

  1. Wide surgical resection and anastomosis.

Evidence (laparoscopic techniques):

The role of laparoscopic techniques [1] [2] [3] [4] in the treatment of colon cancer was examined in a multicenter, prospective, randomized trial (NCCTG-934653, now closed) comparing laparoscopic-assisted colectomy (LAC) to open colectomy.

Treatment Options Under Clinical Evaluation

Adjuvant chemotherapy

The potential value of adjuvant chemotherapy for patients with stage II colon cancer remains controversial. Although subgroups of patients with stage II colon cancer may be at higher-than-average risk for recurrence (including those with anatomic features such as tumor adherence to adjacent structures, perforation, complete obstruction), [5] [6] [7] evidence is inconsistent that adjuvant 5-fluorouracil (5-FU)–based chemotherapy is associated with an improved OS compared with surgery alone. [8]

Features in patients with stage II colon cancer that are associated with an increased risk of recurrence include the following:

The decision to use adjuvant chemotherapy for patients with stage II colon cancer is complicated and requires thoughtful consideration by both patients and their physicians. Adjuvant therapy is not indicated for most patients unless they are entered into a clinical trial.

Evidence (adjuvant chemotherapy):

  1. The GRECCR-03 and NCRI-QUASAR1 trials evaluated the use of systemic or regional chemotherapy or biologic therapy. Following surgery, patients should be considered for entry into a carefully controlled clinical trial.

  2. Investigators from the National Surgical Adjuvant Breast and Bowel Project (NSABP) have indicated that the reduction in risk of recurrence by adjuvant therapy in patients with stage II disease is of similar magnitude to the benefit seen in patients with stage III disease treated with adjuvant therapy, though an OS advantage has not been established. [9]

  3. A meta-analysis of 1,000 stage II patients whose experience was amalgamated from a series of trials indicates a 2% advantage in disease-free survival at 5 years when adjuvant therapy–treated patients treated with 5-FU-leucovorin are compared with untreated controls. [10][Level of evidence: 1iiDii]; [11]

  4. The Cancer Care Ontario Practice Guideline Initiative Gastrointestinal Cancer Disease Site Group undertook a meta-analysis of the English language–published literature consisting of randomized trials in which adjuvant chemotherapy was compared with observation for patients with stage II colon cancer.

Based on these data, the American Society of Clinical Oncology issued a guideline stating “direct evidence from randomized controlled trials does not support the routine use of adjuvant chemotherapy for patients with stage II colon cancer.” [13]

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage II colon cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References:

  1. Bokey EL, Moore JW, Chapuis PH, et al.: Morbidity and mortality following laparoscopic-assisted right hemicolectomy for cancer. Dis Colon Rectum 39 (10 Suppl): S24-8, 1996.
  2. Franklin ME Jr, Rosenthal D, Abrego-Medina D, et al.: Prospective comparison of open vs. laparoscopic colon surgery for carcinoma. Five-year results. Dis Colon Rectum 39 (10 Suppl): S35-46, 1996.
  3. Fleshman JW, Nelson H, Peters WR, et al.: Early results of laparoscopic surgery for colorectal cancer. Retrospective analysis of 372 patients treated by Clinical Outcomes of Surgical Therapy (COST) Study Group. Dis Colon Rectum 39 (10 Suppl): S53-8, 1996.
  4. Weeks JC, Nelson H, Gelber S, et al.: Short-term quality-of-life outcomes following laparoscopic-assisted colectomy vs open colectomy for colon cancer: a randomized trial. JAMA 287 (3): 321-8, 2002.
  5. Lanza G, Matteuzzi M, Gafá R, et al.: Chromosome 18q allelic loss and prognosis in stage II and III colon cancer. Int J Cancer 79 (4): 390-5, 1998.
  6. Jen J, Kim H, Piantadosi S, et al.: Allelic loss of chromosome 18q and prognosis in colorectal cancer. N Engl J Med 331 (4): 213-21, 1994.
  7. Merkel S, Wein A, Günther K, et al.: High-risk groups of patients with Stage II colon carcinoma. Cancer 92 (6): 1435-43, 2001.
  8. Moertel CG, Fleming TR, Macdonald JS, et al.: Intergroup study of fluorouracil plus levamisole as adjuvant therapy for stage II/Dukes' B2 colon cancer. J Clin Oncol 13 (12): 2936-43, 1995.
  9. Mamounas E, Wieand S, Wolmark N, et al.: Comparative efficacy of adjuvant chemotherapy in patients with Dukes' B versus Dukes' C colon cancer: results from four National Surgical Adjuvant Breast and Bowel Project adjuvant studies (C-01, C-02, C-03, and C-04) J Clin Oncol 17 (5): 1349-55, 1999.
  10. Efficacy of adjuvant fluorouracil and folinic acid in B2 colon cancer. International Multicentre Pooled Analysis of B2 Colon Cancer Trials (IMPACT B2) Investigators. J Clin Oncol 17 (5): 1356-63, 1999.
  11. Harrington DP: The tea leaves of small trials. J Clin Oncol 17 (5): 1336-8, 1999.
  12. Figueredo A, Charette ML, Maroun J, et al.: Adjuvant therapy for stage II colon cancer: a systematic review from the Cancer Care Ontario Program in evidence-based care's gastrointestinal cancer disease site group. J Clin Oncol 22 (16): 3395-407, 2004.
  13. Benson AB 3rd, Schrag D, Somerfield MR, et al.: American Society of Clinical Oncology recommendations on adjuvant chemotherapy for stage II colon cancer. J Clin Oncol 22 (16): 3408-19, 2004.

Stage III Colon Cancer Treatment

Stage III colon cancer denotes lymph node involvement. Studies have indicated that the number of lymph nodes involved affects prognosis; patients with one to three involved nodes have a significantly better survival than those with four or more involved nodes.

Standard Treatment Options for Stage III Colon Cancer

Standard treatment options for stage III colon cancer include the following:

  1. Surgery.
  2. Adjuvant chemotherapy.

Surgery

Surgery for stage III colon cancer is wide surgical resection and anastomosis.

Evidence (laparoscopic techniques):

The role of laparoscopic techniques [1] [2] [3] [4] in the treatment of colon cancer was examined in a multicenter, prospective, randomized trial (NCCTG-934653, now closed) comparing laparoscopic-assisted colectomy (LAC) with open colectomy.

Adjuvant chemotherapy

Drug combinations described in this section include the following:

Chemotherapy regimens prior to 2000

Prior to 2000, 5-FU was the only useful cytotoxic chemotherapy in the adjuvant setting for patients with stage III colon cancer. Many of the early randomized studies of 5-FU in the adjuvant setting failed to show a significant improvement in survival for patients. [6] [7] [8] [9] These trials employed 5-FU alone or 5-FU-semustine (methyl-CCNU).

Evidence (5-FU alone and 5-FU-semustine):

  1. The NCCTG conducted a randomized trial comparing surgical resection alone with postoperative levamisole or 5-FU-levamisole. [10][Level of evidence: 1iiA]

  2. In a large confirmatory intergroup trial, 5-FU-levamisole prolonged DFS and OS in patients with stage III colon cancer compared with patients who received no treatment after surgery. [11][Level of evidence: 1iiA] Levamisole alone did not confer these benefits.

  3. Subsequent studies tested the combination of 5-FU-leucovorin in the adjuvant treatment of patients with resected carcinoma of the colon.

  4. The completed Intergroup trial 0089 (INT-0089) randomly assigned 3,794 patients with high-risk stage II or stage III colon cancer to one of the following four treatment arms: [15]

    Results:


  5. In addition to INT-0089, multiple studies have refined the use of 5-FU-leucovorin in the adjuvant setting and can be summarized as follows:

Chemotherapy regimens after 2000

Capecitabine

Capecitabine is an oral fluoropyrimidine that undergoes a three-step enzymatic conversion to 5-FU with the last step occurring in the tumor cell. For patients with metastatic colon cancer, two studies have demonstrated the equivalence of capecitabine to 5-FU-leucovorin. [22] [23]

For patients with stage III colon cancer, capecitabine provides equivalent outcome to intravenous 5-FU and leucovorin.

Evidence (capecitabine):

  1. A multicenter European study compared capecitabine (1,250 mg/m2) administered twice daily for days 1 to 14, then given every 21 days for eight cycles against the Mayo Clinic schedule of 5-FU and low-dose leucovorin for patients with stage III colon cancer. [24]

Oxaliplatin

Oxaliplatin has significant activity when combined with 5-FU-leucovorin in patients with metastatic colorectal cancer.

Evidence (oxaliplatin):

  1. In the 2,246 patients with resected stage II or stage III colon cancer in the completed Multicenter International Study of Oxaliplatin/5-Fluorouracil/Leucovorin in the Adjuvant Treatment of Colon Cancer (MOSAIC [NCT00275210]) study, the toxic effects and efficacy of FOLFOX4 were compared with the same 5-FU-leucovorin regimen without oxaliplatin administered for 6 months. [25] Based on results from the MOSAIC trial, adjuvant FOLFOX4 demonstrated prolonged OS for patients with stage III colon cancer compared with patients receiving 5-FU-leucovorin without oxaliplatin. [26]

FOLFOX has become the reference standard for the next generation of clinical trials for patients with stage III colon cancer. [26]

Treatment Options Under Clinical Evaluation

Eligible patients should be considered for entry into carefully controlled clinical trials comparing various postoperative chemotherapy regimens. [27]

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage III colon cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References:

  1. Bokey EL, Moore JW, Chapuis PH, et al.: Morbidity and mortality following laparoscopic-assisted right hemicolectomy for cancer. Dis Colon Rectum 39 (10 Suppl): S24-8, 1996.
  2. Franklin ME Jr, Rosenthal D, Abrego-Medina D, et al.: Prospective comparison of open vs. laparoscopic colon surgery for carcinoma. Five-year results. Dis Colon Rectum 39 (10 Suppl): S35-46, 1996.
  3. Fleshman JW, Nelson H, Peters WR, et al.: Early results of laparoscopic surgery for colorectal cancer. Retrospective analysis of 372 patients treated by Clinical Outcomes of Surgical Therapy (COST) Study Group. Dis Colon Rectum 39 (10 Suppl): S53-8, 1996.
  4. Schwenk W, Böhm B, Müller JM: Postoperative pain and fatigue after laparoscopic or conventional colorectal resections. A prospective randomized trial. Surg Endosc 12 (9): 1131-6, 1998.
  5. Weeks JC, Nelson H, Gelber S, et al.: Short-term quality-of-life outcomes following laparoscopic-assisted colectomy vs open colectomy for colon cancer: a randomized trial. JAMA 287 (3): 321-8, 2002.
  6. Panettiere FJ, Goodman PJ, Costanzi JJ, et al.: Adjuvant therapy in large bowel adenocarcinoma: long-term results of a Southwest Oncology Group Study. J Clin Oncol 6 (6): 947-54, 1988.
  7. Adjuvant therapy of colon cancer--results of a prospectively randomized trial. Gastrointestinal Tumor Study Group. N Engl J Med 310 (12): 737-43, 1984.
  8. Higgins GA Jr, Amadeo JH, McElhinney J, et al.: Efficacy of prolonged intermittent therapy with combined 5-fluorouracil and methyl-CCNU following resection for carcinoma of the large bowel. A Veterans Administration Surgical Oncology Group report. Cancer 53 (1): 1-8, 1984.
  9. Buyse M, Zeleniuch-Jacquotte A, Chalmers TC: Adjuvant therapy of colorectal cancer. Why we still don't know. JAMA 259 (24): 3571-8, 1988.
  10. Laurie JA, Moertel CG, Fleming TR, et al.: Surgical adjuvant therapy of large-bowel carcinoma: an evaluation of levamisole and the combination of levamisole and fluorouracil. The North Central Cancer Treatment Group and the Mayo Clinic. J Clin Oncol 7 (10): 1447-56, 1989.
  11. Moertel CG, Fleming TR, Macdonald JS, et al.: Levamisole and fluorouracil for adjuvant therapy of resected colon carcinoma. N Engl J Med 322 (6): 352-8, 1990.
  12. Wolmark N, Rockette H, Fisher B, et al.: The benefit of leucovorin-modulated fluorouracil as postoperative adjuvant therapy for primary colon cancer: results from National Surgical Adjuvant Breast and Bowel Project protocol C-03. J Clin Oncol 11 (10): 1879-87, 1993.
  13. Efficacy of adjuvant fluorouracil and folinic acid in colon cancer. International Multicentre Pooled Analysis of Colon Cancer Trials (IMPACT) investigators. Lancet 345 (8955): 939-44, 1995.
  14. O'Connell M, Mailliard J, Macdonald J, et al.: An intergroup trial of intensive course 5FU and low dose leucovorin as surgical adjuvant therapy for high risk colon cancer. [Abstract] Proceedings of the American Society of Clinical Oncology 12: A-552, 190, 1993.
  15. Haller DG, Catalano PJ, Macdonald JS, et al.: Phase III study of fluorouracil, leucovorin, and levamisole in high-risk stage II and III colon cancer: final report of Intergroup 0089. J Clin Oncol 23 (34): 8671-8, 2005.
  16. Wolmark N, Bryant J, Smith R, et al.: Adjuvant 5-fluorouracil and leucovorin with or without interferon alfa-2a in colon carcinoma: National Surgical Adjuvant Breast and Bowel Project protocol C-05. J Natl Cancer Inst 90 (23): 1810-6, 1998.
  17. Wolmark N, Rockette H, Mamounas E, et al.: Clinical trial to assess the relative efficacy of fluorouracil and leucovorin, fluorouracil and levamisole, and fluorouracil, leucovorin, and levamisole in patients with Dukes' B and C carcinoma of the colon: results from National Surgical Adjuvant Breast and Bowel Project C-04. J Clin Oncol 17 (11): 3553-9, 1999.
  18. Okuno SH, Woodhouse CL, Loprinzi CL, et al.: Phase III placebo-controlled clinical trial evaluation of glutamine for decreasing mucositis in patients receiving 5FU (fluorouracil)-base chemotherapy. [Abstract] Proceedings of the American Society of Clinical Oncology 17: A-256, 1998.
  19. Andre T, Colin P, Louvet C, et al.: Semimonthly versus monthly regimen of fluorouracil and leucovorin administered for 24 or 36 weeks as adjuvant therapy in stage II and III colon cancer: results of a randomized trial. J Clin Oncol 21 (15): 2896-903, 2003.
  20. Comparison of flourouracil with additional levamisole, higher-dose folinic acid, or both, as adjuvant chemotherapy for colorectal cancer: a randomised trial. QUASAR Collaborative Group. Lancet 355 (9215): 1588-96, 2000.
  21. Sargent DJ, Goldberg RM, Jacobson SD, et al.: A pooled analysis of adjuvant chemotherapy for resected colon cancer in elderly patients. N Engl J Med 345 (15): 1091-7, 2001.
  22. Van Cutsem E, Twelves C, Cassidy J, et al.: Oral capecitabine compared with intravenous fluorouracil plus leucovorin in patients with metastatic colorectal cancer: results of a large phase III study. J Clin Oncol 19 (21): 4097-106, 2001.
  23. Hoff PM, Ansari R, Batist G, et al.: Comparison of oral capecitabine versus intravenous fluorouracil plus leucovorin as first-line treatment in 605 patients with metastatic colorectal cancer: results of a randomized phase III study. J Clin Oncol 19 (8): 2282-92, 2001.
  24. Twelves C, Wong A, Nowacki MP, et al.: Capecitabine as adjuvant treatment for stage III colon cancer. N Engl J Med 352 (26): 2696-704, 2005.
  25. André T, Boni C, Mounedji-Boudiaf L, et al.: Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer. N Engl J Med 350 (23): 2343-51, 2004.
  26. André T, Boni C, Navarro M, et al.: Improved overall survival with oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment in stage II or III colon cancer in the MOSAIC trial. J Clin Oncol 27 (19): 3109-16, 2009.
  27. Rougier P, Nordlinger B: Large scale trial for adjuvant treatment in high risk resected colorectal cancers. Rationale to test the combination of loco-regional and systemic chemotherapy and to compare l-leucovorin + 5-FU to levamisole + 5-FU. Ann Oncol 4 (Suppl 2): 21-8, 1993.

Stage IV and Recurrent Colon Cancer Treatment

Stage IV colon cancer denotes distant metastatic disease. Treatment of recurrent colon cancer depends on the sites of recurrent disease demonstrable by physical examination and/or radiographic studies. In addition to standard radiographic procedures, radioimmunoscintography may add clinical information that may affect management. [1] Such approaches have not led to improvements in long-term outcome measures such as survival.

Treatment Options for Stage IV and Recurrent Colon Cancer

Treatment options for stage IV and recurrent colon cancer include the following:

  1. Surgical resection of locally recurrent cancer.

  2. Surgical resection and anastomosis or bypass of obstructing or bleeding primary lesions in selected metastatic cases.

  3. Resection of liver metastases in selected metastatic patients (5-year cure rate for resection of solitary or combination metastases exceeds 20%) or ablation in selected patients. [2] [3] [4] [5] [6] [7] [8] [9] [10] [11]

  4. Resection of isolated pulmonary or ovarian metastases in selected patients. [12]

  5. Palliative radiation therapy.

  6. Palliative chemotherapy.

  7. Targeted therapy.

  8. Clinical trials evaluating new drugs and biological therapy.

  9. Clinical trials comparing various chemotherapy regimens or biological therapy, alone or in combination.

Treatment of Liver Metastasis

Approximately 50% of colon cancer patients will be diagnosed with hepatic metastases, either at the time of initial presentation or as a result of disease recurrence. Although only a small proportion of patients with hepatic metastases are candidates for surgical resection, advances in tumor ablation techniques and in both regional and systemic chemotherapy administration provide for a number of treatment options. These include the following:

Surgery

Hepatic metastasis may be considered to be resectable based on the following: [5] [7] [13] [14] [15] [16]

For patients with hepatic metastasis considered to be resectable, a negative margin resection resulted in 5-year survival rates of 25% to 40% in mostly nonrandomized studies, such as the NCCTG-934653 trial. [5] [7] [13] [14] [15] [16] Improved surgical techniques and advances in preoperative imaging have allowed for better patient selection for resection. In addition, multiple studies with multiagent chemotherapy have demonstrated that patients with metastatic disease isolated to the liver, which historically would be considered unresectable, can occasionally be made resectable after the administration of chemotherapy. [17]

Neoadjuvant chemotherapy for unresectable liver metastases

Patients with hepatic metastases that are deemed unresectable will occasionally become candidates for resection if they have a good response to chemotherapy. These patients have 5-year survival rates similar to patients who initially had resectable disease. [17] There is no consensus on the best regimen to use to convert unresectable isolated liver metastases to resectable liver metastases.

Local ablation

Radiofrequency ablation has emerged as a safe technique (2% major morbidity and <1% mortality rate) that may provide for long-term tumor control. [18] [19] [20] [21] [22] [23] [24] Radiofrequency ablation and cryosurgical ablation [25] [26] [27] [28] remain options for patients with tumors that cannot be resected and for patients who are not candidates for liver resection.

Other local ablative techniques that have been used to manage liver metastases include embolization and interstitial radiation therapy. [29] [30] Patients with limited pulmonary metastases, and patients with both pulmonary and hepatic metastases, may also be considered for surgical resection, with 5-year survival possible in highly-selected patients. [12] [31] [32]

Adjuvant or neoadjuvant chemotherapy for resectable liver metastases

The role of adjuvant chemotherapy after potentially curative resection of liver metastases is uncertain.

Evidence (adjuvant or neoadjuvant chemotherapy for resectable liver metastases):

In the era before the use of FOLFOX (folinic acid [LV], 5-fluorouracil [5-FU], and oxaliplatin) and FOLFIRI (5-FU and irinotecan), two trials attempted to randomly assign patients after resection of liver metastases to 5-FU/LV or observation, but both studies were closed early because of poor accrual.

  1. The FFCD-9902 [NCT00304135] trial randomly assigned 173 patients (200 patients were planned) to postoperative 5-FU/LV, which is the Mayo Clinic regimen, or observation. [33]

  2. The European Organization for Research and Treatment of Cancer/National Cancer Institute of Canada/Gruppo Interdisciplinare Valutazione Interventi in Oncologia (EORTC/NCIC/GIVIO) International trial attempted a similar random assignment of patients after surgical resection of liver metastases. The study closed because of poor accrual, and a combined analysis of the study and the FFCD-9902 study was done instead. In the combined analysis, 278 patients (138 of whom received chemotherapy; 14 of whom received surgery alone) were included. [34]

In the era of multiagent chemotherapy, two subsequent studies evaluated its role in the adjuvant setting following resection of liver metastases from colorectal cancer.

  1. A phase III study randomly assigned 306 patients to 2 5-FU/LV or FOLFIRI after a resection of liver metastases. [35]

  2. The EORTC (EORTC-40983 NCT00006479) randomly assigned 364 patients with up to four resectable liver metastases to perioperative FOLFOX (six cycles presurgery and six cycles postsurgery) or surgery alone. [36]

There is no level 1 evidence demonstrating that perioperative or postoperative chemotherapy improves OS for patients undergoing resection of liver metastases. Nevertheless, on the basis of post hoc subset analyses of the EORTC study, some physicians feel perioperative or postoperative therapy is reasonable in this setting.

Intra-arterial chemotherapy after liver resection

Hepatic intra-arterial chemotherapy with floxuridine for liver metastases has produced higher overall response rates but no consistent improvement in survival when compared with systemic chemotherapy. [2] [37] [38] [39] [40] [41] A meta-analysis of the randomized studies, which were all done in the era when only fluoropyrimidines were available for systemic therapy, did not demonstrate a survival advantage. [42]

Evidence (intra-arterial chemotherapy after liver resection):

Two trials evaluated hepatic arterial floxuridine in the adjuvant setting after liver resection.

  1. A trial of hepatic arterial floxuridine and dexamethasone plus systemic 5-FU/LV (compared with systemic 5-FU/LV alone showed improved 2-year PFS (57% vs. 42%, P = .07) and OS (86% vs. 72%, P = .03) but did not show a significant statistical difference in median survival compared with systemic 5-FU therapy alone.

  2. A second trial preoperatively randomly assigned 109 patients who had one to three potentially resectable colorectal hepatic metastases to either no further therapy or postoperative hepatic arterial floxuridine plus systemic 5-FU. [44] Of those randomly assigned patients, 27% were deemed ineligible at the time of surgery, which left only 75 patients evaluable for recurrence and survival.

Further studies are required to evaluate this treatment approach and to determine whether more effective systemic combination chemotherapy alone may provide similar results compared with hepatic intra-arterial therapy plus systemic treatment.

Several studies show increased local toxic effects with hepatic infusional therapy, including liver function abnormalities and fatal biliary sclerosis.

Treatment of Stage IV and Recurrent Colon Cancer

Surgery

Treatment of patients with recurrent or advanced colon cancer depends on the location of the disease. For patients with locally recurrent and/or liver-only and/or lung-only metastatic disease, surgical resection, if feasible, is the only potentially curative treatment.

Chemotherapy and targeted therapy

Currently, there are nine active and approved drugs for patients with metastatic colorectal cancer that are used alone and in combination with other drugs:

Drug combinations described in this section include the following:

5-FU

When 5-FU was the only active chemotherapy drug, trials in patients with locally advanced, unresectable, or metastatic disease demonstrated partial responses and prolongation of the time-to-progression (TTP) of disease [45] [46] as well as improved survival and quality of life for patients receiving chemotherapy, compared with the best supportive care. [47] [48] [49] Several trials have analyzed the activity and toxic effects of various 5-FU-leucovorin regimens using different doses and administration schedules and showed essentially equivalent results with a median survival time in the 12-month range. [50]

Capecitabine

Prior to the advent of multiagent chemotherapy, two randomized studies demonstrated that capecitabine was associated with equivalent efficacy when compared with the Mayo Clinic regimen of 5-FU-leucovorin. [51] [52][Level of evidence: 1iiA]

Irinotecan

Three randomized studies demonstrated improved response rates, PFS, and OS when irinotecan or oxaliplatin was combined with 5-FU-leucovorin. [53] [54] [55]

Evidence (irinotecan):

  1. An intergroup study (NCCTG-N9741) compared IFL with FOLFOX4 in first-line treatment for patients with metastatic colorectal cancer.

  2. Subsequently, two studies compared FOLFOX with FOLFIRI, and patients were allowed to cross over upon progression on first-line therapy, respectively. [56] [57][Level of evidence: 1iiDiii]

  3. The Bolus, Infusional, or Capecitabine with Camptosar-Celecoxib (BICC-C) trial evaluated several different irinotecan-based regimens in patients with previously untreated metastatic colorectal cancer, including FOLFIRI, mIFL, and Capecitabine/irinotecan (CAPIRI). [58][Level of evidence: 1iiA]

Since the publication of these studies, the use of either FOLFOX or FOLFIRI is considered acceptable for first-line treatment of patients with metastatic colorectal cancer.

When using an irinotecan-based regimen as first-line treatment of metastatic colorectal cancer, FOLFIRI is preferred. [58][Level of evidence: 1iiDiii]

Oxaliplatin

Randomized phase III trials have addressed the equivalence of substituting capecitabine for infusional 5-FU. Two phase III studies have evaluated FUOX versus CAPOX. [59] [60]

Evidence (oxaliplatin):

  1. The AIO Colorectal Study Group randomly assigned 474 patients to either FUFOX or CAPOX.

  2. The Spanish Cooperative Group randomly assigned 348 patients to CAPOX or FUOX. [59]

When using an oxaliplatin-based regimen as first-line treatment of metastatic colorectal cancer, a CAPOX regimen is not inferior to a FUOX regimen.

Before the availability of cetuximab, panitumumab, bevacizumab, and aflibercept as second-line therapy, second-line chemotherapy with irinotecan in patients treated with 5-FU/LV as first-line therapy demonstrated improved OS when compared with either infusional 5-FU or supportive care. [61] [62] [63] [64]

Similarly, a phase III trial randomly assigned patients who progressed on irinotecan and 5-FU/LV to bolus and infusional 5-FU/LV (LV5FU2), single-agent oxaliplatin, or FOLFOX4. The median TTP for FOLFOX4 versus LV5FU2 was 4.6 months versus 2.7 months (stratified log-rank test, 2-sided P < .001). [65][Level of evidence: 1iiDiii]

Bevacizumab

Bevacizumab is a partially humanized monoclonal antibody that binds to vascular endothelial growth factor. Bevacizumab can reasonably be added to either FOLFIRI or FOLFOX for patients undergoing first-line treatment of metastatic colorectal cancer.

Evidence (bevacizumab):

  1. After bevacizumab was approved, the BICC-C trial was amended, and an additional 117 patients were randomly assigned to receive FOLFIRI/bevacizumab or mIFL/bevacizumab.

  2. Patients with previously untreated metastatic colorectal cancer were randomly assigned to either IFL or IFL and bevacizumab. [66]

  3. Despite the lack of direct data, in standard practice, bevacizumab was added to FOLFOX as a standard first-line regimen based on the results of the NCCTG-N9741 trial. [67] Subsequently, in a randomized phase III study, patients with untreated stage IV colorectal cancer were randomly assigned in a 2 × 2 factorial design to CAPOX versus FOLFOX4, then to bevacizumab versus placebo. PFS was the primary endpoint.

  4. Investigators from the Eastern Cooperative Oncology Group randomly assigned patients who had progressed on 5-FU-leucovorin and irinotecan to either FOLFOX or FOLFOX and bevacizumab.

Based on these studies, bevacizumab can reasonably be added to either FOLFIRI or FOLFOX for patients undergoing first-line treatment of metastatic colorectal cancer. A major question was whether the use of bevacizumab after first-line therapy was warranted when bevacizumab was used as a component of first-line therapy. At the 2012 American Society of Clinical Oncology Annual Meeting, data was presented from a randomized, controlled trial. [71] In the trial, 820 patients with metastatic colorectal cancer, after progressing on first-line chemotherapy that included bevacizumab, were randomly assigned to chemotherapy without bevacizumab or chemotherapy with bevacizumab. Patients who received bevacizumab experienced an improved OS compared with the patients who did not receive bevacizumab. Median OS was 11.2 months for patients who received bevacizumab plus chemotherapy and 9.8 months for patients who received chemotherapy without bevacizumab (HR, 0.81; 95% CI, 0.69–0.94; unstratified log-rank test, P = .0062). Median PFS was 5.7 months for patients who received bevacizumab plus chemotherapy and 4.1 months for those who received chemotherapy without bevacizumab (HR, 0.68; 95% CI, 0.59–0.78; unstratified log-rank test, P < .0001). [71][Level of evidence: 1iiA]

Aflibercept

Aflibercept is a novel anti-VEGF molecule and has been evaluated as a component of second-line therapy in patients with metastatic colorectal cancer. In one trial, 1,226 patients were randomly assigned to receive aflibercept (4 mg/kg IV) or placebo every 2 weeks in combination with FOLFIRI. [72] Patients who received aflibercept plus FOLFIRI had a significantly improved OS relative to placebo plus FOLFIRI (HR, 0.817; 95.34% CI, 0.713–0.937; P = .0032) with median survival times of 13.50 months versus 12.06 months, respectively. Aflibercept also significantly improved PFS (HR, 0.758; 95% CI, 0.661–0.869; P < .0001), with median PFS times of 6.90 months versus 4.67 months, respectively. On the basis of these results, the use of FOLFIRI plus aflibercept is an acceptable second-line regimen for patients previously treated with FOLFOX-based chemotherapy. [72][Level of evidence: 1A] Whether to continue bevacizumab or initiate aflibercept in second-line therapy has not been addressed as yet in any clinical trial, and there are no data available.

Cetuximab

Cetuximab is a partially humanized monoclonal antibody against the epidermal growth factor receptor (EGFR). Because cetuximab affects tyrosine kinase signaling at the surface of the cell membrane, tumors with mutations causing activation of the pathway downstream of the EGFR, such as KRAS mutations, are not sensitive to its effects. The addition of cetuximab to multiagent chemotherapy improves survival in patients with colon cancers that lack a KRAS mutation (i.e., KRAS wild type). Importantly, patients with mutant KRAS tumors may experience worse outcome when cetuximab is added to multiagent chemotherapy regimens containing bevacizumab.

Evidence (cetuximab):

  1. For patients who have progressed on irinotecan-containing regimens, a randomized, phase II study was performed of either cetuximab or irinotecan and cetuximab.

  2. The Crystal Study (NCT00154102) randomly assigned 1,198 patients with stage IV colorectal cancer to FOLFIRI with or without cetuximab. [74]

  3. In a randomized trial, patients with metastatic colorectal cancer received capecitabine/oxaliplatin/bevacizumab with or without cetuximab. [75]

  4. The Medical Research Council (MRC) (COIN [NCT00182715] trial) sought to answer the question of whether adding cetuximab to combination chemotherapy with a fluoropyrimidine and oxaliplatin in first-line treatment for patients with first-line KRAS wild-type tumors was beneficial. [76] [77]

  5. The OPUS study sought to evaluate the effect of adding cetuximab to first-line treatment with a FOLFOX regimen in an open-labeled, randomized, multicenter, phase II study of patients with EGFR-expressing metastatic colorectal cancer. [78]

Panitumumab

Panitumumab is a fully humanized antibody against the EGFR. The U.S. Food and Drug Administration approved panitumumab for use in patients with metastatic colorectal cancer refractory to chemotherapy. [79] In clinical trials, panitumumab demonstrated efficacy as a single agent or in combination therapy, which was consistent with the effects on PFS and OS with cetuximab. There appears to be a consistent class effect.

Evidence (panitumumab):

  1. In a phase III trial, patients with chemotherapy-refractory colorectal cancer were randomly assigned to panitumumab or best supportive care.

  2. In the PRIME (NCT00364013) study, 1,183 patients were randomly assigned to FOLFOX4 with or without panitumumab as first-line therapy for metastatic colorectal cancer. [80] The study was amended to enlarge the sample size to address patients with the KRAS wild-type tumors and patients with mutant KRAS tumors separately.

  3. Similarly, the addition of panitumumab to a regimen of FOLFOX/bevacizumab resulted in a worse PFS and worse toxicity compared to a regimen of FOLFOX/bevacizumab alone in patients not selected for KRAS mutation in metastatic colon cancer (11.4 months vs. 10.0 months, HR, 1.27; 95% CI, 1.06–1.52). [82][Level of evidence: 1iiDiii]

  4. In another study (NCT00339183), patients with metastatic colorectal cancer who had already received a fluoropyrimidine regimen were randomly assigned to either FOLFIRI or FOLFIRI plus panitumumab. [83]

Regorafenib

Regorafenib is an inhibitor of multiple tyrosine kinase pathways including vascular endothelial growth factor (VEGF). In September 2012, the FDA granted approval for the use of regorafenib in patients who had progressed on prior therapy. The safety and effectiveness of regorafenib were evaluated in a single, clinical study of 760 patients with previously treated metastatic colorectal cancer. [84] Patients were randomly assigned in a 2:1 fashion to receive regorafenib or placebo in addition to best supportive care. Patients treated with regorafenib had a statistically significant improvement in OS (6.4 months in the regorafenib group vs. 5.0 months in the placebo group; HR, 0.77; 95% CI, 0.64–0.94; one-sided P = .0052). [84] [85]

Treatment Options Under Clinical Evaluation

Treatment options under clinical evaluation for stage IV and recurrent colon cancer include the following:

  1. Clinical trials evaluating new drugs and biological therapy.

  2. Clinical trials comparing various chemotherapy regimens or biological therapy, alone or in combination.

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage IV colon cancer and recurrent colon cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References:

  1. Serafini AN, Klein JL, Wolff BG, et al.: Radioimmunoscintigraphy of recurrent, metastatic, or occult colorectal cancer with technetium 99m-labeled totally human monoclonal antibody 88BV59: results of pivotal, phase III multicenter studies. J Clin Oncol 16 (5): 1777-87, 1998.
  2. Wagman LD, Kemeny MM, Leong L, et al.: A prospective, randomized evaluation of the treatment of colorectal cancer metastatic to the liver. J Clin Oncol 8 (11): 1885-93, 1990.
  3. Scheele J, Stangl R, Altendorf-Hofmann A: Hepatic metastases from colorectal carcinoma: impact of surgical resection on the natural history. Br J Surg 77 (11): 1241-6, 1990.
  4. Scheele J, Stangl R, Altendorf-Hofmann A, et al.: Indicators of prognosis after hepatic resection for colorectal secondaries. Surgery 110 (1): 13-29, 1991.
  5. Adson MA, van Heerden JA, Adson MH, et al.: Resection of hepatic metastases from colorectal cancer. Arch Surg 119 (6): 647-51, 1984.
  6. Coppa GF, Eng K, Ranson JH, et al.: Hepatic resection for metastatic colon and rectal cancer. An evaluation of preoperative and postoperative factors. Ann Surg 202 (2): 203-8, 1985.
  7. Gayowski TJ, Iwatsuki S, Madariaga JR, et al.: Experience in hepatic resection for metastatic colorectal cancer: analysis of clinical and pathologic risk factors. Surgery 116 (4): 703-10; discussion 710-1, 1994.
  8. Fernández-Trigo V, Shamsa F, Sugarbaker PH: Repeat liver resections from colorectal metastasis. Repeat Hepatic Metastases Registry. Surgery 117 (3): 296-304, 1995.
  9. Jaeck D, Bachellier P, Guiguet M, et al.: Long-term survival following resection of colorectal hepatic metastases. Association Française de Chirurgie. Br J Surg 84 (7): 977-80, 1997.
  10. Taylor M, Forster J, Langer B, et al.: A study of prognostic factors for hepatic resection for colorectal metastases. Am J Surg 173 (6): 467-71, 1997.
  11. Elias D, Cavalcanti A, Sabourin JC, et al.: Resection of liver metastases from colorectal cancer: the real impact of the surgical margin. Eur J Surg Oncol 24 (3): 174-9, 1998.
  12. Girard P, Ducreux M, Baldeyrou P, et al.: Surgery for lung metastases from colorectal cancer: analysis of prognostic factors. J Clin Oncol 14 (7): 2047-53, 1996.
  13. Hughes KS, Simon R, Songhorabodi S, et al.: Resection of the liver for colorectal carcinoma metastases: a multi-institutional study of patterns of recurrence. Surgery 100 (2): 278-84, 1986.
  14. Schlag P, Hohenberger P, Herfarth C: Resection of liver metastases in colorectal cancer--competitive analysis of treatment results in synchronous versus metachronous metastases. Eur J Surg Oncol 16 (4): 360-5, 1990.
  15. Rosen CB, Nagorney DM, Taswell HF, et al.: Perioperative blood transfusion and determinants of survival after liver resection for metastatic colorectal carcinoma. Ann Surg 216 (4): 493-504; discussion 504-5, 1992.
  16. Fong Y, Fortner J, Sun RL, et al.: Clinical score for predicting recurrence after hepatic resection for metastatic colorectal cancer: analysis of 1001 consecutive cases. Ann Surg 230 (3): 309-18; discussion 318-21, 1999.
  17. Leonard GD, Brenner B, Kemeny NE: Neoadjuvant chemotherapy before liver resection for patients with unresectable liver metastases from colorectal carcinoma. J Clin Oncol 23 (9): 2038-48, 2005.
  18. Rossi S, Buscarini E, Garbagnati F, et al.: Percutaneous treatment of small hepatic tumors by an expandable RF needle electrode. AJR Am J Roentgenol 170 (4): 1015-22, 1998.
  19. Solbiati L, Livraghi T, Goldberg SN, et al.: Percutaneous radio-frequency ablation of hepatic metastases from colorectal cancer: long-term results in 117 patients. Radiology 221 (1): 159-66, 2001.
  20. Lencioni R, Goletti O, Armillotta N, et al.: Radio-frequency thermal ablation of liver metastases with a cooled-tip electrode needle: results of a pilot clinical trial. Eur Radiol 8 (7): 1205-11, 1998.
  21. Curley SA, Izzo F, Delrio P, et al.: Radiofrequency ablation of unresectable primary and metastatic hepatic malignancies: results in 123 patients. Ann Surg 230 (1): 1-8, 1999.
  22. Oshowo A, Gillams A, Harrison E, et al.: Comparison of resection and radiofrequency ablation for treatment of solitary colorectal liver metastases. Br J Surg 90 (10): 1240-3, 2003.
  23. Livraghi T, Solbiati L, Meloni F, et al.: Percutaneous radiofrequency ablation of liver metastases in potential candidates for resection: the "test-of-time approach". Cancer 97 (12): 3027-35, 2003.
  24. Pawlik TM, Izzo F, Cohen DS, et al.: Combined resection and radiofrequency ablation for advanced hepatic malignancies: results in 172 patients. Ann Surg Oncol 10 (9): 1059-69, 2003.
  25. Jarnagin WR, Fong Y, Ky A, et al.: Liver resection for metastatic colorectal cancer: assessing the risk of occult irresectable disease. J Am Coll Surg 188 (1): 33-42, 1999.
  26. Ravikumar TS, Kaleya R, Kishinevsky A: Surgical ablative therapy of liver tumors. Cancer: Principles and Practice of Oncology Updates 14 (3): 1-12, 2000.
  27. Seifert JK, Morris DL: Prognostic factors after cryotherapy for hepatic metastases from colorectal cancer. Ann Surg 228 (2): 201-8, 1998.
  28. Bageacu S, Kaczmarek D, Lacroix M, et al.: Cryosurgery for resectable and unresectable hepatic metastases from colorectal cancer. Eur J Surg Oncol 33 (5): 590-6, 2007.
  29. Thomas DS, Nauta RJ, Rodgers JE, et al.: Intraoperative high-dose rate interstitial irradiation of hepatic metastases from colorectal carcinoma. Results of a phase I-II trial. Cancer 71 (6): 1977-81, 1993.
  30. Ravikumar TS: Interstitial therapies for liver tumors. Surg Oncol Clin N Am 5 (2): 365-77, 1996.
  31. McAfee MK, Allen MS, Trastek VF, et al.: Colorectal lung metastases: results of surgical excision. Ann Thorac Surg 53 (5): 780-5; discussion 785-6, 1992.
  32. Headrick JR, Miller DL, Nagorney DM, et al.: Surgical treatment of hepatic and pulmonary metastases from colon cancer. Ann Thorac Surg 71 (3): 975-9; discussion 979-80, 2001.
  33. Portier G, Elias D, Bouche O, et al.: Multicenter randomized trial of adjuvant fluorouracil and folinic acid compared with surgery alone after resection of colorectal liver metastases: FFCD ACHBTH AURC 9002 trial. J Clin Oncol 24 (31): 4976-82, 2006.
  34. Mitry E, Fields AL, Bleiberg H, et al.: Adjuvant chemotherapy after potentially curative resection of metastases from colorectal cancer: a pooled analysis of two randomized trials. J Clin Oncol 26 (30): 4906-11, 2008.
  35. Ychou M, Hohenberger W, Thezenas S, et al.: A randomized phase III study comparing adjuvant 5-fluorouracil/folinic acid with FOLFIRI in patients following complete resection of liver metastases from colorectal cancer. Ann Oncol 20 (12): 1964-70, 2009.
  36. Nordlinger B, Sorbye H, Glimelius B, et al.: Perioperative chemotherapy with FOLFOX4 and surgery versus surgery alone for resectable liver metastases from colorectal cancer (EORTC Intergroup trial 40983): a randomised controlled trial. Lancet 371 (9617): 1007-16, 2008.
  37. Kemeny N, Daly J, Reichman B, et al.: Intrahepatic or systemic infusion of fluorodeoxyuridine in patients with liver metastases from colorectal carcinoma. A randomized trial. Ann Intern Med 107 (4): 459-65, 1987.
  38. Chang AE, Schneider PD, Sugarbaker PH, et al.: A prospective randomized trial of regional versus systemic continuous 5-fluorodeoxyuridine chemotherapy in the treatment of colorectal liver metastases. Ann Surg 206 (6): 685-93, 1987.
  39. Rougier P, Laplanche A, Huguier M, et al.: Hepatic arterial infusion of floxuridine in patients with liver metastases from colorectal carcinoma: long-term results of a prospective randomized trial. J Clin Oncol 10 (7): 1112-8, 1992.
  40. Kemeny N, Cohen A, Seiter K, et al.: Randomized trial of hepatic arterial floxuridine, mitomycin, and carmustine versus floxuridine alone in previously treated patients with liver metastases from colorectal cancer. J Clin Oncol 11 (2): 330-5, 1993.
  41. Reappraisal of hepatic arterial infusion in the treatment of nonresectable liver metastases from colorectal cancer. Meta-Analysis Group in Cancer. J Natl Cancer Inst 88 (5): 252-8, 1996.
  42. Mocellin S, Pilati P, Lise M, et al.: Meta-analysis of hepatic arterial infusion for unresectable liver metastases from colorectal cancer: the end of an era? J Clin Oncol 25 (35): 5649-54, 2007.
  43. Kemeny N, Huang Y, Cohen AM, et al.: Hepatic arterial infusion of chemotherapy after resection of hepatic metastases from colorectal cancer. N Engl J Med 341 (27): 2039-48, 1999.
  44. Kemeny MM, Adak S, Gray B, et al.: Combined-modality treatment for resectable metastatic colorectal carcinoma to the liver: surgical resection of hepatic metastases in combination with continuous infusion of chemotherapy--an intergroup study. J Clin Oncol 20 (6): 1499-505, 2002.
  45. Petrelli N, Herrera L, Rustum Y, et al.: A prospective randomized trial of 5-fluorouracil versus 5-fluorouracil and high-dose leucovorin versus 5-fluorouracil and methotrexate in previously untreated patients with advanced colorectal carcinoma. J Clin Oncol 5 (10): 1559-65, 1987.
  46. Petrelli N, Douglass HO Jr, Herrera L, et al.: The modulation of fluorouracil with leucovorin in metastatic colorectal carcinoma: a prospective randomized phase III trial. Gastrointestinal Tumor Study Group. J Clin Oncol 7 (10): 1419-26, 1989.
  47. Scheithauer W, Rosen H, Kornek GV, et al.: Randomised comparison of combination chemotherapy plus supportive care with supportive care alone in patients with metastatic colorectal cancer. BMJ 306 (6880): 752-5, 1993.
  48. Expectancy or primary chemotherapy in patients with advanced asymptomatic colorectal cancer: a randomized trial. Nordic Gastrointestinal Tumor Adjuvant Therapy Group. J Clin Oncol 10 (6): 904-11, 1992.
  49. Buyse M, Thirion P, Carlson RW, et al.: Relation between tumour response to first-line chemotherapy and survival in advanced colorectal cancer: a meta-analysis. Meta-Analysis Group in Cancer. Lancet 356 (9227): 373-8, 2000.
  50. Leichman CG, Fleming TR, Muggia FM, et al.: Phase II study of fluorouracil and its modulation in advanced colorectal cancer: a Southwest Oncology Group study. J Clin Oncol 13 (6): 1303-11, 1995.
  51. Van Cutsem E, Twelves C, Cassidy J, et al.: Oral capecitabine compared with intravenous fluorouracil plus leucovorin in patients with metastatic colorectal cancer: results of a large phase III study. J Clin Oncol 19 (21): 4097-106, 2001.
  52. Hoff PM, Ansari R, Batist G, et al.: Comparison of oral capecitabine versus intravenous fluorouracil plus leucovorin as first-line treatment in 605 patients with metastatic colorectal cancer: results of a randomized phase III study. J Clin Oncol 19 (8): 2282-92, 2001.
  53. Saltz LB, Cox JV, Blanke C, et al.: Irinotecan plus fluorouracil and leucovorin for metastatic colorectal cancer. Irinotecan Study Group. N Engl J Med 343 (13): 905-14, 2000.
  54. de Gramont A, Figer A, Seymour M, et al.: Leucovorin and fluorouracil with or without oxaliplatin as first-line treatment in advanced colorectal cancer. J Clin Oncol 18 (16): 2938-47, 2000.
  55. Douillard JY, Cunningham D, Roth AD, et al.: Irinotecan combined with fluorouracil compared with fluorouracil alone as first-line treatment for metastatic colorectal cancer: a multicentre randomised trial. Lancet 355 (9209): 1041-7, 2000.
  56. Tournigand C, André T, Achille E, et al.: FOLFIRI followed by FOLFOX6 or the reverse sequence in advanced colorectal cancer: a randomized GERCOR study. J Clin Oncol 22 (2): 229-37, 2004.
  57. Colucci G, Gebbia V, Paoletti G, et al.: Phase III randomized trial of FOLFIRI versus FOLFOX4 in the treatment of advanced colorectal cancer: a multicenter study of the Gruppo Oncologico Dell'Italia Meridionale. J Clin Oncol 23 (22): 4866-75, 2005.
  58. Fuchs CS, Marshall J, Mitchell E, et al.: Randomized, controlled trial of irinotecan plus infusional, bolus, or oral fluoropyrimidines in first-line treatment of metastatic colorectal cancer: results from the BICC-C Study. J Clin Oncol 25 (30): 4779-86, 2007.
  59. Díaz-Rubio E, Tabernero J, Gómez-España A, et al.: Phase III study of capecitabine plus oxaliplatin compared with continuous-infusion fluorouracil plus oxaliplatin as first-line therapy in metastatic colorectal cancer: final report of the Spanish Cooperative Group for the Treatment of Digestive Tumors Trial. J Clin Oncol 25 (27): 4224-30, 2007.
  60. Porschen R, Arkenau HT, Kubicka S, et al.: Phase III study of capecitabine plus oxaliplatin compared with fluorouracil and leucovorin plus oxaliplatin in metastatic colorectal cancer: a final report of the AIO Colorectal Study Group. J Clin Oncol 25 (27): 4217-23, 2007.
  61. Rothenberg ML, Eckardt JR, Kuhn JG, et al.: Phase II trial of irinotecan in patients with progressive or rapidly recurrent colorectal cancer. J Clin Oncol 14 (4): 1128-35, 1996.
  62. Conti JA, Kemeny NE, Saltz LB, et al.: Irinotecan is an active agent in untreated patients with metastatic colorectal cancer. J Clin Oncol 14 (3): 709-15, 1996.
  63. Rougier P, Van Cutsem E, Bajetta E, et al.: Randomised trial of irinotecan versus fluorouracil by continuous infusion after fluorouracil failure in patients with metastatic colorectal cancer. Lancet 352 (9138): 1407-12, 1998.
  64. Cunningham D, Pyrhönen S, James RD, et al.: Randomised trial of irinotecan plus supportive care versus supportive care alone after fluorouracil failure for patients with metastatic colorectal cancer. Lancet 352 (9138): 1413-8, 1998.
  65. Rothenberg ML, Oza AM, Bigelow RH, et al.: Superiority of oxaliplatin and fluorouracil-leucovorin compared with either therapy alone in patients with progressive colorectal cancer after irinotecan and fluorouracil-leucovorin: interim results of a phase III trial. J Clin Oncol 21 (11): 2059-69, 2003.
  66. Hurwitz H, Fehrenbacher L, Novotny W, et al.: Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 350 (23): 2335-42, 2004.
  67. Sanoff HK, Sargent DJ, Campbell ME, et al.: Five-year data and prognostic factor analysis of oxaliplatin and irinotecan combinations for advanced colorectal cancer: N9741. J Clin Oncol 26 (35): 5721-7, 2008.
  68. Saltz LB, Clarke S, Díaz-Rubio E, et al.: Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: a randomized phase III study. J Clin Oncol 26 (12): 2013-9, 2008.
  69. Cassidy J, Clarke S, Díaz-Rubio E, et al.: Randomized phase III study of capecitabine plus oxaliplatin compared with fluorouracil/folinic acid plus oxaliplatin as first-line therapy for metastatic colorectal cancer. J Clin Oncol 26 (12): 2006-12, 2008.
  70. Giantonio BJ, Catalano PJ, Meropol NJ, et al.: High-dose bevacizumab improves survival when combined with FOLFOX4 in previously treated advanced colorectal cancer: results from the Eastern Cooperative Oncology Group (ECOG) study E3200. [Abstract] J Clin Oncol 23 (Suppl 16): A-2, 1s, 2005.
  71. Arnold D, Andre T, Bennouna J, et al.: Bevacizumab (BEV) plus chemotherapy (CT) continued beyond first progression in patients with metastatic colorectal cancer (mCRC) previously treated with BEV plus CT: results of a randomized phase III intergroup study (TML study). [Abstract] J Clin Oncol 30 (Suppl 15): A-CRA3503, 2012.
  72. Van Cutsem E, Tabernero J, Lakomy R, et al.: Addition of aflibercept to fluorouracil, leucovorin, and irinotecan improves survival in a phase III randomized trial in patients with metastatic colorectal cancer previously treated with an oxaliplatin-based regimen. J Clin Oncol 30 (28): 3499-506, 2012.
  73. Cunningham D, Humblet Y, Siena S, et al.: Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med 351 (4): 337-45, 2004.
  74. Van Cutsem E, Köhne CH, Hitre E, et al.: Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. N Engl J Med 360 (14): 1408-17, 2009.
  75. Tol J, Koopman M, Cats A, et al.: Chemotherapy, bevacizumab, and cetuximab in metastatic colorectal cancer. N Engl J Med 360 (6): 563-72, 2009.
  76. Maughan TS, Adams RA, Smith CG, et al.: Addition of cetuximab to oxaliplatin-based first-line combination chemotherapy for treatment of advanced colorectal cancer: results of the randomised phase 3 MRC COIN trial. Lancet 377 (9783): 2103-14, 2011.
  77. Adams RA, Meade AM, Seymour MT, et al.: Intermittent versus continuous oxaliplatin and fluoropyrimidine combination chemotherapy for first-line treatment of advanced colorectal cancer: results of the randomised phase 3 MRC COIN trial. Lancet Oncol 12 (7): 642-53, 2011.
  78. Bokemeyer C, Cutsem EV, Rougier P, et al.: Addition of cetuximab to chemotherapy as first-line treatment for KRAS wild-type metastatic colorectal cancer: pooled analysis of the CRYSTAL and OPUS randomised clinical trials. Eur J Cancer 48 (10): 1466-75, 2012.
  79. Van Cutsem E, Peeters M, Siena S, et al.: Open-label phase III trial of panitumumab plus best supportive care compared with best supportive care alone in patients with chemotherapy-refractory metastatic colorectal cancer. J Clin Oncol 25 (13): 1658-64, 2007.
  80. Douillard JY, Siena S, Cassidy J, et al.: Randomized, phase III trial of panitumumab with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) versus FOLFOX4 alone as first-line treatment in patients with previously untreated metastatic colorectal cancer: the PRIME study. J Clin Oncol 28 (31): 4697-705, 2010.
  81. Douillard JY, Oliner KS, Siena S, et al.: Panitumumab-FOLFOX4 treatment and RAS mutations in colorectal cancer. N Engl J Med 369 (11): 1023-34, 2013.
  82. Hecht JR, Mitchell E, Chidiac T, et al.: A randomized phase IIIB trial of chemotherapy, bevacizumab, and panitumumab compared with chemotherapy and bevacizumab alone for metastatic colorectal cancer. J Clin Oncol 27 (5): 672-80, 2009.
  83. Peeters M, Price TJ, Cervantes A, et al.: Randomized phase III study of panitumumab with fluorouracil, leucovorin, and irinotecan (FOLFIRI) compared with FOLFIRI alone as second-line treatment in patients with metastatic colorectal cancer. J Clin Oncol 28 (31): 4706-13, 2010.
  84. Grothey A, Sobrero AF, Siena S, et al.: Results of a phase III randomized, double-blind, placebo-controlled, multicenter trial (CORRECT) of regorafenib plus best supportive care (BSC) versus placebo plus BSC in patients (pts) with metastatic colorectal cancer (mCRC) who have progressed after standard therapies. [Abstract] J Clin Oncol 30 (Suppl 4): A-LBA385, 2012.
  85. Grothey A, Van Cutsem E, Sobrero A, et al.: Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet 381 (9863): 303-12, 2013.

Changes to This Summary (06/05/2014)

The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.

General Information About Colon Cancer

Updated statistics with estimated new cases and deaths for 2014 (cited American Cancer Society as reference 1).

Added text to state that limited data and no level 1 evidence are available to guide patients and physicians about surveillance and management of patients after surgical resection and adjuvant therapy. The American Society of Clinical Oncology and the National Comprehensive Cancer Network recommend specific surveillance and follow-up strategies (cited Meyerhardt et al. and Benson et al. as references 25 and 26, respectively).

Revised text to state that to date, no large-scale randomized trials have documented an overall survival (OS) benefit for standard, postoperative monitoring program.

Added Factors Associated with Recurrence as a new subsection.

Stage IV and Recurrent Colon Cancer Treatment

Revised text of subsection title to read Neoadjuvant chemotherapy for unresectable liver metastases.

Added text to state that there is no consensus on the best regimen to use to convert unresectable isolated liver metastases to resectable liver metastases.

Revised text of subsection title to read Adjuvant or neoadjuvant chemotherapy for resectable liver metastases.

Revised Adjuvant or neoadjuvant chemotherapy for resectable liver metastases subsection.

Added text to provide evidence about intra-arterial chemotherapy after liver resection and included statistics related to two trials that evaluated hepatic arterial floxuridine in the adjuvant setting after liver resection (cited 1999 Kemeny et al. as reference 43 and level of evidence IiiA and 2002 Kemeny as reference 44).

Added text to state that further studies are required to evaluate this treatment approach and to determine whether more effective systemic combination chemotherapy alone may provide similar results compared with hepatic intra-arterial therapy plus systemic treatment.

Added text to include regorafenib to list of nine active and approved drugs for patients with metastatic colorectal cancer.

Revised text to state that before the availability of cetuximab, panitumumab, bevacizumab, and aflibercept as second-line therapy, second-line chemotherapy with irinotecan in patients treated with 5-FU/LV as first-line therapy demonstrated improved OS when compared with either infusional 5-FU or supportive care.

Added text to state that a retrospective analysis evaluated patients with wild-type KRAS exon 2 status for other KRAS and BRAF mutations. Of the 620 patients who were initially identified as not having a mutation in exon 2 of KRAS, 108 patients were found to have additional RAS mutations and 53 patients were found to have BRAF mutations. In a retrospective analysis, patients without any RAS or BRAF mutations had a longer PFS and OS when assigned to the oxaliplatin, 5-FU and LV (FOLFOX-4) and panitumumab arm than the patients assigned to the FOLFOX-4 arm (cited Douillard et al. as reference 81 and level of evidence 3iiiA).

Revised text to state that patients were randomly assigned in a 2:1 fashion to receive regorafenib or placebo in addition to best supportive care; also updated statistics showing a significant improvement in OS for patients treated with regorafenib (cited Grothey et al. as reference 85).

This summary is written and maintained by the PDQ Adult Treatment Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ NCI's Comprehensive Cancer Database pages.

About This PDQ Summary

Purpose of This Summary

This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of colon cancer. It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.

Reviewers and Updates

This summary is reviewed regularly and updated as necessary by the PDQ Adult Treatment Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).

Board members review recently published articles each month to determine whether an article should:

Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.

The lead reviewers for Colon Cancer Treatment are:

Any comments or questions about the summary content should be submitted to Cancer.gov through the Web site's Contact Form. Do not contact the individual Board Members with questions or comments about the summaries. Board members will not respond to individual inquiries.

Levels of Evidence

Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Adult Treatment Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations.

Permission to Use This Summary

PDQ is a registered trademark. Although the content of PDQ documents can be used freely as text, it cannot be identified as an NCI PDQ cancer information summary unless it is presented in its entirety and is regularly updated. However, an author would be permitted to write a sentence such as “NCI’s PDQ cancer information summary about breast cancer prevention states the risks succinctly: [include excerpt from the summary].”

The preferred citation for this PDQ summary is:

National Cancer Institute: PDQ® Colon Cancer Treatment. Bethesda, MD: National Cancer Institute. Date last modified <MM/DD/YYYY>. Available at: http://cancer.gov/cancertopics/pdq/treatment/colon/HealthProfessional. Accessed <MM/DD/YYYY>.

Images in this summary are used with permission of the author(s), artist, and/or publisher for use within the PDQ summaries only. Permission to use images outside the context of PDQ information must be obtained from the owner(s) and cannot be granted by the National Cancer Institute. Information about using the illustrations in this summary, along with many other cancer-related images, is available in Visuals Online, a collection of over 2,000 scientific images.

Disclaimer

Based on the strength of the available evidence, treatment options may be described as either “standard” or “under clinical evaluation.” These classifications should not be used as a basis for insurance reimbursement determinations. More information on insurance coverage is available on Cancer.gov on the Coping with Cancer: Financial, Insurance, and Legal Information page.

Contact Us

More information about contacting us or receiving help with the Cancer.gov Web site can be found on our Contact Us for Help page. Questions can also be submitted to Cancer.gov through the Web site’s Contact Form.

Get More Information From NCI

Call 1-800-4-CANCER

For more information, U.S. residents may call the National Cancer Institute's (NCI's) Cancer Information Service toll-free at 1-800-4-CANCER (1-800-422-6237) Monday through Friday from 8:00 a.m. to 8:00 p.m., Eastern Time. A trained Cancer Information Specialist is available to answer your questions.

Chat online

The NCI's LiveHelp® online chat service provides Internet users with the ability to chat online with an Information Specialist. The service is available from 8:00 a.m. to 11:00 p.m. Eastern time, Monday through Friday. Information Specialists can help Internet users find information on NCI Web sites and answer questions about cancer.

Write to us

For more information from the NCI, please write to this address:

Search the NCI Web site

The NCI Web site provides online access to information on cancer, clinical trials, and other Web sites and organizations that offer support and resources for cancer patients and their families. For a quick search, use the search box in the upper right corner of each Web page. The results for a wide range of search terms will include a list of "Best Bets," editorially chosen Web pages that are most closely related to the search term entered.

There are also many other places to get materials and information about cancer treatment and services. Hospitals in your area may have information about local and regional agencies that have information on finances, getting to and from treatment, receiving care at home, and dealing with problems related to cancer treatment.

Find Publications

The NCI has booklets and other materials for patients, health professionals, and the public. These publications discuss types of cancer, methods of cancer treatment, coping with cancer, and clinical trials. Some publications provide information on tests for cancer, cancer causes and prevention, cancer statistics, and NCI research activities. NCI materials on these and other topics may be ordered online or printed directly from the NCI Publications Locator. These materials can also be ordered by telephone from the Cancer Information Service toll-free at 1-800-4-CANCER (1-800-422-6237).

Date last modified: 2014-06-05

Sponsors:
The following organisations have financed parts of our PhD research project on improving the quality of online cancer information.

This site does not accept advertisemets.

Back to the Cancer.gov contents overview
Questions? Mail them to us!

This website is certified by Health On the Net Foundation. Click
      to verify.This site complies with the HONcode standard for trustworthy health information:
verify here.

Dr. G. Quade
This page was last modified on Donnerstag, 24-Jul-2014 04:14:29 CEST
Impressum