Adjuvant Therapy for Stage II Colon Cancer

Publication Date: December 20, 2021

Treatment

Recommendation 1.1

Adjuvant chemotherapy (ACT) should not routinely be offered to patients with stage II colon cancer. (CB, H, M, S)
Note: See Recommendations 1.3 and 1.4 for scenarios where ACT may be appropriate for specific subgroups of patients with stage II colon cancer.
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Recommendation 1.2

ACT should not routinely be offered to patients who are at low risk for recurrence, including patients with stage IIA (T3) tumors with at least 12 sampled lymph nodes of the surgical specimen, tumors without perineural or lymphatic invasion, poor or undifferentiated tumor grade, clinical intestinal obstruction, tumor perforation, and less than grade BD3 tumor budding. (EB, H, L, W)
Qualifying statement:
There is no compelling evidence to suggest that age of patient should alter this recommendation. Specifically, there is no evidence that younger low risk stage II patients should be offered ACT based on their age alone.
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Recommendation 1.3

ACT should be offered to patients with stage IIB and stage IIC colon cancer (i.e., T4, lesions either penetrating visceral peritoneum or invasive of surrounding organ, respectively), with a discussion of the potential benefits and risks of harm associated with ACT. (EB, B, M, W)
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Recommendation 1.4

ACT may be offered to patients with stage IIA (i.e., T3) colon cancer with high-risk features, including sampling of fewer than 12 lymph nodes in the surgical specimen, perineural or lymphatic invasion, poorly or undifferentiated tumor grade, intestinal obstruction, tumor perforation, and/or grade BD3 tumor budding (≥10 buds). (EB, B, L, W)
Qualifying statements:
  • The number of risk factors should be considered as part of the shared-decision making process. The presence of more than one risk factor may increase the risk of recurrence; in an exploratory analysis of IDEA collaboration data, 5-year disease free survival (DFS) was 74.8% for stage II patients with 2 or more risk factors, compared to 87.3% for patients with one risk factor.
  • Circulating tumor DNA (ctDNA) was identified as an emerging potential predictive factor, however, insufficient evidence of predictive value of chemotherapy was available to warrant its inclusion in the list of high-risk features within the main recommendation. The Expert Panel anticipates that data on ctDNA will be forthcoming through prospective clinical trials, and included in a future version of this guideline.
  • The Expert Panel notes that there is controversy around the timing of chemotherapy; data on this topic were not reported in the included observational studies. In the Multicenter International Study of Oxaliplatin/5-Fluorouracil/Leucovorin in the Adjuvant Treatment of Colon Cancer (MOSAIC) trial of oxaliplatin in addition to fluoropyrimidine-based chemotherapy, patients were required to have started ACT within 7 weeks of surgery. In the Quick and Simple and Reliable (QUASAR) trial of ACT with FU and folinic acid, therapy was initiated within 6 weeks of surgery, where possible.
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Recommendation 2.1

Adjuvant fluoropyrimidine-only chemotherapy is not routinely recommended for patients with deficient mismatch repair (dMMR)/microsatellite instability (MSI) tumors. (EB, H, M, S)
Qualifying statements:
  • For patients with dMMR or MSI and T4 tumors and/or other high-risk features (with the exception of poor differentiation), oxaliplatin containing chemotherapy may be considered (see Recommendation 3.1, qualifying statements). This qualifying statement is based on indirect evidence of a DFS benefit with the addition of oxaliplatin in the population of patients with stage II or stage III colon cancer in the MOSAIC trial.
  • Poor differentiation is not considered a high-risk prognostic factor in patients with dMMR or MSI tumors.
  • Patients with proficient mismatch repair (pMMR)/microsatellite stable (MSS) tumors are included within Recommendations 1.1 to 1.4.
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Recommendation 3.1

There is insufficient evidence to routinely recommend the addition of oxaliplatin to fluoropyrimidine-based chemotherapy for patients with high-risk stage II colon cancer. (EB, B, L, W)
Qualifying statements:
  • The Expert Panel notes the significant time to recurrence benefit with oxaliplatin-containing ACT in exploratory analyses of the MOSAIC trial. The Panel recommends a shared-decision making approach to guide choice of therapy that includes discussion of potential for benefit and risks of harm with the addition of oxaliplatin to fluoropyrimidine-based chemotherapy.
  • As stated in the qualifying statement to Recommendation 2.1, for patients with dMMR or MSI who have T4 tumors and/or other high-risk features (with the exception of poor differentiation), when shared decision-making results in the choice to proceed with ACT, the Expert Panel recommends oxaliplatin-containing chemotherapy. This statement is based on indirect evidence of benefit in the combined population of patients with stage II and III colon cancer.
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Recommendation 4.1

In patients who are candidates for adjuvant doublet chemotherapy, adjuvant oxaliplatin-containing chemotherapy may be offered for a duration of 3 months or 6 months, after a discussion with the patient of the potential benefits and risks of harm associated with the options for treatment duration. (EB, B, L, W)
Note: Recommendation 4.1 is based on a subgroup analysis of four randomized trials from the IDEA collaboration. Choice of therapy with CAPOX or FOLFOX was non-randomized, and made by treating clinicians prior to randomization to 3- or 6-months duration of treatment. In high-risk stage II patients, five-year DFS, the primary study outcome, was 81.7% vs. 82.0% (p = .09) with 3 vs. 6 months of CAPOX, respectively (hazard ratio [HR], 1.02; 80% confidence interval [CI], 0.88 to 1.17). Five-year DFS was 79.2% vs. 86.5% (p = .88) with 3 months vs. 6 months of FOLFOX, respectively (HR, 1.41; 80% CI, 1.18 to 1.68). Among all patients, the prevalence of peripheral neuropathy of grade 2 or higher during treatment was 13% vs. 36% with 3 months vs. 6 months of treatment, respectively. These findings should be considered during the shared decision-making process.
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Recommendation Grading

Disclaimer

Overview

Title

Adjuvant Therapy for Stage II Colon Cancer

Authoring Organization

Publication Month/Year

December 20, 2021

Document Type

Guideline

Country of Publication

US

Inclusion Criteria

Male, Female, Adult, Older adult

Health Care Settings

Ambulatory, Outpatient, Radiology services

Intended Users

Nurse, nurse practitioner, physician, physician assistant

Scope

Treatment, Management

Diseases/Conditions (MeSH)

D003110 - Colonic Neoplasms

Keywords

colon cancer, colorectal cancer, CRC, stage II

Supplemental Methodology Resources

Data Supplement, Evidence Tables

Methodology

Number of Source Documents
71
Literature Search Start Date
June 1, 2018
Literature Search End Date
April 1, 2021