Adjuvant Chemotherapy Decreases Recurrences in Stage II Colorectal Cancer
by Dr.C.H. Weaver M.D. updated 9/1/2018
Adjuvant chemotherapy may improve disease-free and overall survival for some but not individuals diagnosed with stage II colon cancer. Research suggests it should be considered for patients with higher risk features.
Characteristics that may indicate a higher risk of recurrence include the following:,
- 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.
These reccomendations are based on several clinical studies.
According to a pivotal clinical trial published in Lancet Oncology, chemotherapy for Stage II colorectal cancer appears to provide a modest improvement in survival.
Colorectal cancer remains the second leading cause of cancer-related deaths in the United States. Stage II (or B) colorectal cancer refers to cancer that has penetrated the wall of the colon but has not spread to any nearby lymph nodes and is not detectable elsewhere in the body.
Depending on specific characteristics of the cancer, 60–75% of patients are cured without evidence of recurrence following surgery alone. However, despite undergoing complete surgical removal of the cancer, disease recurs in 25–40% of patients with Stage II colorectal cancer.
Typically, cancer recurs because small amounts of cancer that had spread outside the colon were not removed by surgery. These cancer cells cannot be detected with currently available tests. Such undetectable areas of cancer outside the colon are referred to as micrometastases, and they cause the relapses that follow surgical treatment. In order to improve the cure rate achieved with surgical removal of the cancer, an effective treatment is needed to cleanse the body of micrometastases.
The effectiveness of chemotherapy administered following surgery (adjuvant chemotherapy) for Stage II colorectal cancer has been debated; results regarding its ability to improve survival for this group of patients have been inconsistent. Adjuvant chemotherapy is used to kill micrometastasis to reduce recurrences and ultimately improve outcomes. But because no clear results regarding adjuvant chemotherapy in Stage II colorectal cancer have been established, researchers continue to evaluate this treatment approach.
Researchers recently conducted a clinical study to further evaluate adjuvant chemotherapy in the treatment of Stage II colorectal cancer. The study, referred to as the QUASAR study, included 3,239 patients with Stage II colorectal cancer who were treated with surgery followed by adjuvant chemotherapy (consisting of a 5-fluorouracil-based regimen) or with no further treatment. Median follow-up was five and a half years.
- The five-year survival was improved by 3.5% among patients who received adjuvant chemotherapy compared with those who did not receive adjuvant therapy.
- The risk of recurrences was reduced by approximately 22% among patients treated with adjuvant chemotherapy.
The researchers concluded that adjuvant chemotherapy in Stage II colorectal cancer is associated with a modest though significant improvement in survival.
Patients diagnosed with Stage II colorectal cancer may wish to speak with their physician regarding their individual risks and benefits of chemotherapy.
The Lancet publication appears to confirm a previously reported clinical trial from the European Society of Clinical Oncology demonstrating a small benefit for patients with stage II colorectal cancer.
This study compared treatment with chemotherapy with observation alone in 3,238 patients diagnosed with colorectal cancer. The study participants were primarily stage II colon cancer patients (92%) and were considered by their physician to be questionable in their need for chemotherapy. The population included both colon (71%) and rectal cancer patients. Patients were treated with 5-fluorouracil (5-FU) and leucovorin, either daily for 5 days or once weekly with a larger dose. Various high and low doses of leucovorin were also given with and without levamisole. Previous studies had shown that different 5-FU schedules and the dose of leucovorin, as well as whether or not levamisole was used, had all resulted in therapeutically equal results. These findings allowed for the variance in treatment regimen within this current study.
Results of the study found that the risk of recurrence was decreased (4%) and overall survival was improved modestly (13%) from treatment with 5-FU and leucovorin. Further analysis found that neither the stage of the disease nor the site of colon cancer changed the treatment efficacy. Rectal cancer patients, however, did have a greater reduction in risk than the colon cancer patients (32% vs. 23%). In addition, it was noted that the relative survival benefit for chemotherapy was almost zero in patients over the age of 70.
Given the modest benefit of adjuvant chemotherapy for the treatment of stage II colo-rectal cancer have tried to identify risk factors that may predict cancer recurrences following surgery.
Researchers from Germany recently analyzed disease characteristics and outcome data in over 300 patients diagnosed with stage II colon cancer who were treated with surgery alone. Researchers found the following disease characteristics predicted a significantly increased risk of cancer recurrence following surgery.
- Emergency presentation (bowel perforation or bowel obstruction)
- “left-sided” initial cancer site (descending colon)
- Greater depth of invasion of the cancer.
The researchers performing this analysis suggest that patients with one or more of these disease characteristics may be appropriate candidates for adjuvant chemotherapy. However, further research on this subject needs to be conducted, including evaluation of surgeons and/or surgical institutions as separate variables. Patients with early-stage colon cancer should speak with a medical and surgical oncologist about the possible benefits from adjuvant chemotherapy.
- Figuerdo A, Coombes ME, Mukherjee S. Adjuvant therapy for completely resected stage II colon cancer.Cochrane Database of Systematic Reviews. 2008;(3):CD005390.
 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.
 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.
 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.
QUASAR Collaborative Group. Adjuvant chemotherapy versus observation in patients with colorectal cancer: a randomized study. Lancet Oncology. 2007;370:2020-2029.
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.
Kerr D, Barnwell J, Hills R, et al. QUASAR Collaborative Group: a randomized study of adjuvant chemotherapy (CT) Vs Observation in Predominately Stage II Colorectal Cancer. Presented at the 2004 Congress of the European Society of Clinical Oncology. Annals of Oncology. 2004;15,supplement 3:iii12, abstract 43IN.
Cancer, Vol 92, Issue 6, pp 1435-1443, 200.