Stage I-III Colon Cancer

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The treatment of early stage colon cancer consists of surgery followed by systemic adjuvant chemotherapy in individuals at risk of cancer recurrence.1,2,3,4

Following surgical removal of colon cancer, the cancer is classified as:

  • Stage I colon cancer is confined to the lining of the colon, does not penetrate the wall of the colon into the abdominal cavity, and has not spread to any adjacent organs or local lymph nodes. Approximately 90% of patients are cured with surgery alone and will not experience a cancer recurrence.3
  • Stage II colon cancer has penetrated the wall of the colon into the abdominal cavity but does not invade any of the local lymph nodes – 25-40% of stage II patients will experience recurrence following surgery and systemic adjuvant therapy is recommended for some patients to reduce this risk.3
  • Stage III colon cancer has penetrated the wall of the colon into the abdominal cavity and invaded any of the local lymph nodes. Half of patients will experience recurrence following surgery and systemic adjuvant therapy is recommended to most patients to reduce this risk.3

The following is a general overview of the treatment of stage I – III colon cancer. The information on this Web site is intended to help educate you about treatment options and to facilitate a shared decision-making process with your treating physician.

Systemic Adjuvant Therapy

The delivery of systemic treatment following local treatment with surgery is referred to as “adjuvant” therapy and may include chemotherapy or precision cancer medicines. Systemic adjuvant chemotherapy is commonly recommended for some patients with stage II and most patients with stage III colon cancer. The goal of systemic adjuvant therapy is to reduce the risk of colon cancer recurrence.1,2,3,4,5,6,7

Stage II Colon Cancer

Adjuvant chemotherapy may delay cancer progression and prolong survival in some but not all patients with stage II colon cancer. Characteristics that may indicate a higher risk of recurrence in stage II cancer include the following:3,4

  • High grade cells on pathologic exam.
  • Less than 12 lymph nodes sampled during surgery.
  • Perforation or obstruction of the colon due to cancer.
  • Stage IIB tumors (tumor has extended beyond the wall of the colon).

OncotypeDX Testing

The OncotypeDX test that may help determine prognosis for patients with stage II colon cancer. This estimates the risk of cancer recurrence by evaluating the activity of certain genes in a sample of tumor tissue. Risk of recurrence can vary among patients with colon cancer and use of the Oncotype DX test in combination with other markers of risk may help to individualize treatment decisions.4

Stage III Colon Cancer

Systemic adjuvant chemotherapy is administered to patients with stage III colon cancer because it reduces the risk of cancer recurrence and improves survival.3,4,5,6,7

Since the 1980’s, the mainstay of chemotherapy treatment has been 5-flourouracil (5-FU) and leucovorin (LV), which is very well tolerated by most patients. Adding Eloxatin® (oxaliplatin) to 5-FU/LV improves (FOLFOX) survival rates by 5-10%

Xeloda® (capecitabine) is a form of the chemotherapy drug 5-FU that is administered orally as a pill, rather than into a vein and appears to work as well as 5-FU/LV with fewer side effects. In addition, oral administration is more convenient since it requires fewer clinic visits—patients receiving Xeloda will make a minimum of eight trips to their clinic, whereas those on 5-FU may make up to 30 trips.5

Adjuvant Chemotherapy Regimens for Colon Cancer

  • FOLFOX (LV/5-fluorouracil + Eloxatin (oxaliplatin)
  • CAPEOX (Xeloda (capecitabine) + Eloxatin
  • Xeloda

The overall health of the patient must be considered when weighing the risks and benefits of adjuvant therapy. Patients with fewer other health problems (such as diabetes, obesity or heart disease) will better tolerate adjuvant chemotherapy.

In order to reduce neuropathy, a significant and troublesome side effect of Eloxatin The American Society of Clinical Oncology released guidelines that states that patients with clinically low-risk stage II-III colon cancer should have the option of receiving 3 months of adjuvant Eloxatin-based chemotherapy instead of 6 months.

Resulting recommendations of therapy duration apply to patients with completely resected stage III colon cancer who are being offered adjuvant chemotherapy with Eloxatin and a fluoropyrimidine.

For patients at a high risk of recurrence (T4 and/or N2), adjuvant chemotherapy should be offered for a duration of 6 months.

For patients at a low risk of recurrence (T1, T2, or T3 and N1), either 6 months of adjuvant chemotherapy or a shorter duration of 3 months may be offered on the basis of a potential reduction in adverse events and no significant difference in disease-free survival with the 3-month regimen.

Furthermore, the panel recommends a shared decision-making approach on a case-by-case basis in determining duration of therapy. Decision-makers should take into account patient characteristics, values and preferences, and other factors including a discussion of the potential for benefit and risks of harm associated with treatment duration, the guideline states.8,9

Treatment of the Older Individuals

A large percentage of patients with colon cancer are 65 years or older. Sometimes elderly patients and/or their physicians may believe that treatment will be more toxic for elderly patients than it is for their younger counterparts. Due to this perceived intolerability of therapy, elderly patients often do not receive optimal treatment. The results of several clinical trials however confirm that elderly patients with colon cancer who are in otherwise good health tolerate chemotherapy as well as younger patients and experience improved survival from its use.10,11,12,13,14,15

Strategies to Improve Treatment

Genetic Mutations

Not all colon cancer cells are alike. They may differ from one another based on what genes have mutations. Molecular testing is performed to test for certain genetic mutations or the proteins they produce because the results can help select treatment including newer precision cancer medicines designed to attack specific colon cancer cells with specific genetic mutations. Doctors will increasingly use genomic testing to help better identify who will benefit from adjuvant therapy.

References

1 D Sargent, R Goldberg, J MacDonald, et al. Adjuvant Chemotherapy for Colon Cancer (CC) Is Beneficial Without Significantly Increased Toxicity in Elderly Patients (Pts): Results from a 3351 Pt Meta -Analysis. Proceedings from the 36th annual meeting of the American Society of Clinical Oncology. Blood. 2000;19: Abstract #933.

2 http://ascopubs.org/doi/abs/10.1200/JCO.2017.35.4_suppl.710

3 Journal of Clinical Oncology (online April 15, 2019; doi:10.1200/JCO.19.00281).

4 O’Connell M, Lee M, Lopatin M et al. Validation of the 12-gene colon cancer recurrence score (RS) in NSABP C07 as a predictor of recurrence in stage II and III colon cancer patients treated with 5FU/LV (FU) and 5FU/LV+oxaliplatin (FU+Ox). Paper presented at: 2012 Annual Meeting of the American Society of Clinical Oncology; June 1-5, 2012;Chicago,IL. Abstract 3512.

5 Andre T, Boni C, Mounedji-Boudiaf, et al. Oxaliplatin, Fluorouracil, and Leucovorin as Adjuvant Treatment for Colon Cancer. New England Journal of Medicine. 2004;350:2343-2351.

6 Twelves C, Wong A, Nowacki M, et al. Capecitabine as Adjuvant Treatment for Stage III Colon Cancer. New England Journal of Medicine. 2005; 352:2696-2704.

7 Taieb J, Puig PL, Bedenne L. Cetuximab plus FOLFOX-4 for fully resected stage III colon carcinoma: scientific background and the ongoing PETACC-8 trial. Expert Reviews of Anticancer Therapy.2008;8(2):183-9.

8 Grothey, A. et al. (2018) Duration of Adjuvant Chemotherapy for Stage III Colon Cancer. The New England Journal of Medicine.

9 Iveson, T. et al. (2018) 3 versus 6 months of adjuvant oxaliplatin-fluoropyrimidine combination therapy for colorectal cancer (SCOT): an international, randomised, phase 3, non-inferiority trial.

10 Goldberg RM, Tabah-Risch I, Bleiberg H et al. Pooled Analysis of Safety and Efficacy of Oxaliplatin Plus Fluorouracil/Leucovorin Administered Bimonthly in Elderly Patients with Colorectal Cancer. Journal of Clinical Oncology. 2006;24:4085-4091.

11 Sanoff HK, Carpenter WR, Stürmer T, et al. Effect of adjuvant chemotherapy on survival of patients with stage III colon cancer diagnosed after age 75 years. Journal of Clinical Oncology. 2012; 30(21): 2624-2634.

12 http://abstracts.asco.org/199/AbstView_199_194502.html

13 Mirza MS, Longman RJ, Farrokhyar F, et al. Long-term outcomes for laparoscopic versus open resection of nonmetastatic colorectal cancer. Journal of Laparoendoscopic Advances in Surgical Technique2008;18(5):679-685.

14 Bilimoria KY, Bentrem DJ, Merkow RP, et al. Laparoscopic-assisted vs. Open Colectomy for Cancer: Comparison of Short-term Outcomes from 121 Hospitals. Journal of Gastrointestinal Surgery [early online publication]. June, 2008.

15 Nelson H, Sargent D, Wie H, et al. A Comparison of Laparoscopically Assisted and Open Colectomy for Colon Cancer. New England Journal of Medicine 2004;350:2050-2059.