Following surgical removal of colon cancer, the cancer is referred to as Stage II if the final pathology report shows that the cancer has penetrated the wall of the colon into the abdominal cavity, but does not invade any of the local lymph nodes and cannot be detected in other locations in the body.
Stage II adenocarcinoma of the colon is a common and curable cancer. Depending on features of the cancer, 60-75% of patients are cured without evidence of cancer recurrence following treatment with surgery alone. Stage II cancer can be further divided into two stages, Stage IIA and Stage IIB. In Stage IIA, the tumor has grown through the outermost layers of the colon but is confined to the colon. In Stage IIB, the tumor has grown through the colon wall and has extended to adjacent tissues or organs. In both stages, there are no lymph nodes containing tumor cells and no distant metastases.
Despite undergoing complete surgical removal of the cancer, 25-40% of patients with Stage II colon carcinoma experience recurrence of their cancer. Typically, cancer recurs because there are small amounts of cancer that had spread outside the colon and were not removed by surgery. These cancer cells cannot be detected with any of the currently available tests. Undetectable areas of cancer outside the colon are referred to as micrometastases. The presence of micrometastases causes the relapses that follow surgical treatment. An effective treatment is needed to eliminate micrometastases and improve cure rates of Stage II cancer. Efforts are currently underway to find such a therapy.
The following is a general overview of treatment for Stage II colon cancer. Treatment may consist of surgery, radiation, chemotherapy and/or targeted therapy (drugs which act by a different mechanism than chemotherapy to target tumor cells). Multi-modality treatment, which is treatment using two or more techniques, is increasingly recognized as an important approach for increasing a patient’s chance of cure or prolonging survival. In some cases, participation in a clinical trial utilizing new, innovative therapies may provide the most promising treatment. Circumstances unique to each patient’s situation may influence how these general treatment principles are applied and whether the patient decides to receive treatment. The potential benefits of multi-modality care, participation in a clinical trial, or standard treatment must be carefully balanced with the potential risks. The information on this website is intended to help educate patients about their treatment options and to facilitate a mutual or shared decision-making process with their treating cancer physician.
The delivery of cancer treatment following local treatment with surgery is referred to as “adjuvant” therapy and may include chemotherapy, radiation therapy, and/or targeted therapy. Adjuvant chemotherapy improves outcomes among patients with Stage III colon cancer, but the benefits among patients with Stage II colon cancer are less clear. A review of previously published clinical trials reported that adjuvant chemotherapy may improve disease-free survival, but does not appear to improve overall survival, among patients with Stage II colon cancer.1 Routine use of adjuvant chemotherapy is not recommended for patients with Stage II colon cancer, but it may be considered for some patients, particularly those whose cancers have high-risk features.2
Characteristics that may indicate a higher risk of recurrence 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)
The overall health of the patient must also 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.
Oncotype DX Testing
A newer test that may help guide treatment decisions for patients with Stage II colon cancer is the Oncotype DX colon cancer test. This test—which is similar to a test that is commonly used for patients with early-stage breast cancer—is performed after surgery but before final decisions are made about adjuvant (post-surgery) therapy. The test estimates the risk of cancer recurrence by evaluating the activity of certain genes in a sample of tumor tissue. Risk of recurrence can vary greatly among patients with Stage II colon cancer, and use of the Oncotype DX test in combination with other markers of risk may help to individualize treatment decisions.
TREATMENT OF THE ELDERLY
A large percentage of patients with colon cancer are 65 years or older. Sometimes elderly patients and/or their physicians may believe that 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.
To explore the risks and benefits of chemotherapy by age, researchers analyzed data from 7 separate clinical trials that were conducted to evaluate adjuvant chemotherapy in patients with Stage II or III colon cancer. Patients were divided into four age groups: 50 years and younger, 51 to 60 years, 61 to 70 years and 70 years and older. In these trials, patients received either surgery alone or surgery followed by adjuvant chemotherapy consisting of either fluorouracil plus leucovorin or fluorouracil plus levamisole. Five years following treatment, the overall survival rate was 71% for patients treated with adjuvant chemotherapy versus only 64% for those treated with surgery alone. There were no differences in survival rates between the age groups. The incidence of side effects from adjuvant chemotherapy was not increased in the elderly, except for one clinical trial reporting a higher rate of leukopenia (low white blood cell levels) in the elderly group. The analysis from this large sum of data confirms that elderly patients with colon cancer who are in otherwise good health tolerate chemotherapy as well as younger patients.5
STRATEGIES TO IMPROVE TREATMENT
The development of more effective cancer treatments requires that new and innovative therapies be evaluated with cancer patients. Clinical trials are studies that evaluate the effectiveness of new drugs or treatment strategies. Future progress in the treatment of Stage II colon cancer will result from the continued evaluation of new treatments in clinical trials. Participation in a clinical trial may offer patients access to better treatments and advance the existing knowledge about treatment of this cancer. Patients who are interested in participating in a clinical trial should discuss the risks and benefits of clinical trials with their physician. Areas of active exploration to improve the treatment of Stage II colon cancer include the following:
New Adjuvant Chemotherapy
Several new chemotherapy and biological drugs demonstrate promising activity for the treatment of colon cancer. Clinical research is ongoing to develop new multi-drug treatment regimens that incorporate new anti-cancer therapies for use as adjuvant treatment. Eloxatin® (oxaliplatin) and Xeloda® (capecitabine) are chemotherapy drugs that have been recently approved for the treatment of Stage III colon cancer and may provide benefit in the adjuvant treatment of Stage II disease.
Eloxatin® (oxaliplatin): Eloxatin is a platinum-based chemotherapy drug that was approved for the treatment of advanced colon cancer in early 2004. In the treatment of patients with Stage II or Stage III colon cancer that had been completely removed with surgery, adjuvant treatment with Eloxatin®/5-FU/LV (FOLFOX) helped patients survive longer without cancer than 5FU/LV. This was a large trial that involved 2246 patients, half of which were treated with Eloxatin plus 5-FU/LV and the other half were treated with 5-FU/LV. The Stage II patients who received Eloxatin experienced fewer cancer-related events and approximately 87% were disease-free for 3 years or more, compared to 84% who did not receive Eloxatin.6 Eloxatin is now FDA-approved for the adjuvant treatment of Stage III colon cancer. Since doctors can prescribe medication for treatment of conditions other than that which they are approved, some patients with Stage II colon cancer may be able to receive treatment with Eloxatin.
Xeloda® (capecitabine): Xeloda is a form of the chemotherapy drug fluorouracil that is administered orally, as a pill, rather than into a vein. Intravenous (IV) drug administration is associated with more side effects than oral administration. Side effects of IV fluorouracil may include pain and infection at the injection site. Current research evaluating Xeloda in the treatment of various cancers indicates comparable efficacy to 5-FU in colorectal cancer 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 go up to 30 times.7 Xeloda has been FDA-approved for the treatment of Stage III colon cancer and may also benefit patients with Stage II disease.
Advances in Surgery for Colon Cancer
Surgical removal of cancer remains an integral part of the treatment strategy for patients with Stage II colon cancer and many patients are cured with this treatment alone. Conventional surgery involves opening the pelvis and/or abdomen to gain access to the large intestine. As with any surgery, there are risks associated with removing cancer, including infection, blood loss, and other possible complications of surgery.
Clinical trials have shown that a less invasive surgical technique, called laparoscopic surgery, may be more tolerable than and similarly effective as conventional surgery. Laparoscopic surgery involves the placement of small probes into the area of surgery. The probes contain cameras and instruments for removing the cancer. The surgeon performs the surgery through the probes while watching his or her movements captured by the camera and projected on a large screen. This type of procedure prevents the need for large surgical incisions, and may be associated with fewer complications, especially infections (abdominal infections, urinary tract infections and pneumonia). In addition, patients undergoing laparoscopic surgery generally experience less discomfort post-operatively and have a quicker recovery time (return to normal activities).
A recent study of 233 patients in the United Kingdom evaluated the long-term survival rates of open resection compared with laparoscopic resection. The overall survival rates were similar in both groups, but traditional, open surgery was associated with a lower cumulative recurrence rate.8 The results mean that patients undergoing traditional surgery had a lower rate of cancer recurrence compared with the laparoscopic group.
An analysis of over 100 hospitals and 3,000 patients has shown that laparoscopic surgery is better tolerated in the short term compared with open abdominal surgery in the short term. Laparoscopic patients stayed fewer days in the hospital and had fewer infections.9
Another investigation of laparoscopic surgery for colon cancer involved 872 patients; approximately half of the patients underwent laparoscopic surgery to remove their cancer, and the other half underwent conventional surgery. The number of patients that experienced a recurrence of their cancer and the number of patients that survived three years or more were approximately the same for both procedures. Patients who underwent laparoscopic surgery spent one less day in the hospital and required less pain medication compared to patients that underwent standard surgery.10
When choosing between open and laparoscopic abdominal surgery, patients and their doctors must weigh the potential short-term benefits of laparoscopic surgery with a possible small increase in cancer recurrence that may be associated with laparoscopic resection. Patients may choose based on their own health and the expertise and recommendations of their surgeon.
Targeted therapies are anticancer drugs that interfere with specific pathways involved in cancer cell growth or survival. Some targeted therapies block growth signals from reaching cancer cells; others reduce the blood supply to cancer cells; and still others stimulate the immune system to recognize and attack the cancer cell. Depending on the specific “target”, targeted therapies may slow cancer cell growth or increase cancer cell death. Targeted therapies may be used in combination with other cancer treatments such as conventional chemotherapy.
Avastin® (bevacizumab): Avastin is type of targeted therapy that slows or prevents the growth of new blood vessels, a process called angiogenesis. Cancer cells require food, oxygen, and proteins in order to grow and spread. New blood vessels are necessary to deliver these essential components of cellular growth. Avastin starves cancer cells by inhibiting angiogenesis. Avastin has been shown to improve outcomes among patients with metastatic colon cancer,11 and is being studied among patients with earlier-stage colon cancer as well.
Erbitux® (cetuximab): Erbitux is a type of targeted therapy called a monoclonal antibody. It works by binding to a protein receptor located on many cancer cells called the epidermal growth factor receptor (EGFR). EGFR is involved in cellular growth and replication, and by targeting EGFR, the spread of cancer can be reduced or delayed.
Erbitux administered alone or with the chemotherapy drug Camptosar® (irinotecan) has been shown to improve survival for patients with advanced, EGFR-positive colorectal cancer that has progressed on first line therapy.12 13
Managing Side Effects
Techniques designed to prevent or control the side effects of cancer and its treatments are called supportive care. Side effects not only cause patients discomfort, but also may prevent the delivery of therapy at its planned dose and schedule. In order to achieve optimal outcomes from treatment and improve quality of life, it is imperative that treatment is delivered as planned and that side effects resulting from cancer and its treatment are appropriately managed. For more information, go to Managing Side Effects.
1 Figuerdo A, Coombes ME, Mukherjee S. Adjuvant therapy for completely resected stage II colon cancer.Cochrane Database of Systematic Reviews. 2008;(3):CD005390.
2 Benson AB, Schrag D, Somerfield MR. American Society of Clinical Oncology recommendations on adjuvant chemotherapy for stage II colon cancer. Journal of Clinical Oncology. 2004;15:3408-19.
3 Benson A, Schrag D, Somerfield M, et al. American Society of Clinical Oncology recommendations on adjuvant chemotherapy for stage II colon cancer. Journal of Clinical Oncology. 2004; 22: 3408-3419.
4 Figueredo A, Charette M, 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. Journal of Clinical Oncology. 2004;22: 3395-3407.
5 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.
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8 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 Technique 2008;18(5):679-685.
9 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.
10 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.
11 Hurwitz H, Fehrenbacher L, Novotny W, et al. Bevacizumab plus Irinotecan, Fluorouracil, and Leucovorin for Metastatic Colorectal Cancer. New England Journal of Medicine. 2004;350:2335-2342.
12 Cunningham D, Humblet Y, Siena S, et al. Cetuximab Monotherapy and Cetuximab plus Irinotecan in Irinotecan-Refractory Metastatic Colorectal Cancer. New England Journal of Medicine 2004;351:337-345.
13 Hriesik C, Ramanathan R, Hughes S. Update for Surgeons: recent and noteworthy changes in therapeutic regimens for cancer of the colon and rectum. Journal of the American College of Surgeons2007; 205: 468-478.