In 2022, it is estimated that in Canada, 24300 people will develop colorectal cancer (13500 males and 10800 females). 1 A patient may be predisposed to develop colorectal cancer by a hereditary condition (e.g.: hereditary non-polyposis colon cancer, familial adenomatous polyposis) or a personal history of either inflammatory bowel disease (e.g.: Crohn's disease, ulcerative colitis) or adenomatous polyps. Over 60 percent of colorectal cancers are without a clearly identifiable predisposing factor, however.
In the absence of hereditary cancer syndromes, the progression from adenoma to adenocarcinoma occurs sporadically as a result of acquired genetic alterations. Allelic loss, chromosomal amplifications, or translocations account for 85 percent of such cases. In the other 15 percent, epigenetic silencing of a component of the DNA mismatch repair system allows frame-shift mutations and base-pair substitutions to persist. The resultant accumulation of tandemly repeated nucleotide sequences ("microsatellites") facilitate further changes during replication ("genetic instability"). While most microsatellites fail to occur within regulatory genes, microsatellites within critical coding regions of genes involved in the regulation of cell growth predispose to loss of function of a tumor suppressor genes or to the gain of function of an oncogene.
Patients with tumours that display "high-frequency microsatellite instability" achieve a better five-year overall survival than patients with tumours that display microsatellite stability or low-frequency instability (HR 0.31, CI95% 0.14-0.72, p = 0.004). 2 The use of adjuvant 5-Fluorouracil and Leucovorin chemotherapy fails to improve overall survival in patients with tumours that display high-frequency microsatellite instability (HR 1.07, CI95% 0.62-1.86, p = 0.80).
After a diagnosis of colorectal cancer, prognosis depends upon the stage at diagnosis; that is, prognosis is better with less penetration of tumour into the bowel wall, fewer involved regional lymph nodes, and no evidence of metastatic disease.
Because the prognosis is better when colorectal cancer is identified at an earlier stage, because of the relatively high incidence of colorectal cancer, and because of the simplicity and accuracy of screening tests, screening for colorectal cancer represents an important component of routine care for all adults aged fifty years or older. This is especially important in patients with first-degree relatives with colorectal cancer.

# Search Strategy
This guideline was developed to promote evidence-based practice in Alberta. It was compiled from the results of randomized controlled trials and systematic reviews, derived from an English language and relevant term search of PubMed and MEDLINE from 1990 forward. It takes into consideration related information presented at local, national, and international meetings as well as the Alberta Provincial Gastrointestinal Tumour Team's interpretation of the data. For the 2023 update of this guideline, recommendations were modified based on a consensus discussion at the 2023 Annual Gastrointestinal Tumour Team Meeting. However, no formal update of the literature was performed.

# Target Population
The recommendations outlined in this guideline apply to adults over the age of 18 years with early stage colon cancer. Different principles may apply to pediatric patients.

# Recommendations and Discussion

# Suggested Diagnostic Work-Up
- Prior to an attempt at resection of an intraluminal mass, it is recommended that, in the absence of a complete bowel obstruction, a colonoscopy be completed to exclude synchronous neoplasms. - A CT scan of the thorax, abdomen, and pelvis is recommended to exclude the possibility of metastatic disease and to provide a baseline for the surveillance CT scans. To evaluate an abnormality identified on CT scan, further imaging (e.g.: MR, ultrasound) may be required. - A pre-operative CEA is recommended for future comparison. A post-operative CEA should be requested to ensure that it has normalized if it was elevated before surgery. ASCO recommends tumour budding should be assessed pre-operatively as well, however, at this time we believe the evidence is not strong enough to recommend adjuvant chemotherapy solely based on high levels of tumour budding. 3 - 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. 4

# Goal of Therapy
To render the patient free of disease and to delay or prevent recurrence.
- After surgical resection of the tumour, the patient's need for adjuvant chemotherapy should be defined based upon the stage and the medical oncologist's assessment of the patient's relevant comorbidities (e.g.: diabetes mellitus, hypertension, cardiac status, etc.). The presence of at least one high-risk feature should prompt consideration for systemic adjuvant chemotherapy in stage II disease. 2. Ideally, adjuvant chemotherapy should be initiated as soon as possible (once the patient has recovered from surgery). 5 If this is not possible due to post-operative complications, adjuvant chemotherapy could still be considered up to twelve weeks after surgery. 3. Consider treatment on a clinical trial, if available. 4. To optimize the care of patients with resected colon cancer, the patient's case should be reviewed with the multidisciplinary team. Refer to "Capecitabine: A Guide for Patient Care." NO16968 demonstrated an improvement in both the disease-free survival (66.1% versus 59.8%, HR 0.80, CI95% 0.69-0.93, p = 0.0045) and relapse-free survival (67.8% versus 60.9%, HR 0.78, CI95% 0.67-0.92, p = 0.0024) when compared 5-Fluorouracil and Leucovorin by either the Mayo or Roswell Park regimens. Although overall survival was not statistically significantly superior (77.6% versus 74.2%, HR 0.87, CI95% 0.72-1.05, p = 0.1486), the Kaplan-Meier curves continue to separate. Modified FOLFOX6 12,21 This regimen requires placement of a central venous catheter (CVC), peripherally inserted central catheter (PICC line), or port. For the subset of patients with stage III disease, the MOSAIC trial suggested that the addition of Oxaliplatin to 5-Fluorouracil and Leucovorin improves five-year disease-free (66.4% versus 58.9%, HR 0.78, CI95% 0.65-0.93, p = 0.005) and six-year overall survival (72.9% versus 68.7%, HR 0.80, CI95% 0.65-0.97, p = 0.023). The benefit of Oxaliplatin in patients over seventy years of age has been questioned. 20 Capecitabine 22 Refer to "Capecitabine: A Guide for Patient Care." Capecitabine has been shown to be equally efficacious as, but less toxic and less resource intensive than, the "Mayo Regimen" (see below). The optimal duration of Oxaliplatin-based adjuvant chemotherapy (CAPOX or FOLFOX) is 6 months. Based on the primary analysis of the IDEA collaboration, the non-inferiority of 3 months is not proven (HR1.07 95% CI 1.00-1.15) using a non-inferiority margin 1.12. 23 However, given the cumulative-dose dependent toxicity of oxaliplatin, 24 a duration of 3 months may be considered in select patients after an informed discussion about the relative risks and benefits (Shi, JCO, 2017). Based on sub-group analyses from the IDEA collaboration, both regimen and risk group can be considered, though not randomized (regimen and risk group) or pre-planned (risk group) (Shi, JCO, 2017

# Appendix B: Chemotherapy Dosing and Schedule
Chemotherapy Dose/Schedule CAPOX/XELOX Eight three-week cycles where Oxaliplatin 130 mg/m 2 is administered IV Q21d and Capecitabine 1,000 mg/m 2 is administered PO Q12h for fourteen days. FOLFOX Twelve two-week cycles where - Oxaliplatin (85 mg/m 2 IV over two hours) and Leucovorin (400 mg/m 2 IV over two to six hours) are administered concurrently, - Followed by 5-Fluorouracil (400 mg/m 2 IV bolus),
- Followed by a continuous intravenous infusion of 5-Fluorouracil (2,400 mg/m 2 over forty-six hours).
Eight three-week cycles where Capecitabine 1,250 mg/m 2 is administered PO Q12h for fourteen days.

# Development and Revision History
This guideline was developed by a multidisciplinary working group comprised of members from the Alberta Provincial GI Tumour Team, external participants identified by the Working Group Lead, and a methodologist from the Guideline Resource Unit. The draft guideline was externally reviewed and endorsed by members of the Alberta Provincial GI Tumour Team who were not involved in the guideline's development, including surgical oncologists, radiation oncologists, medical oncologists, gastroenterologists, nurses, pathologists, and pharmacists. A detailed description of the methodology followed during the guideline development process can be found in the Guideline Resource Unit Handbook.
This guideline was originally developed in 2008.

# Levels of Evidence