The recommendations contained in this guideline are a consensus of the Alberta Provincial GI Tumour Team and are a synthesis of currently accepted approaches to management, derived from a review of relevant scientific literature. Clinicians applying these guidelines should, in consultation with the patient, use independent medical judgment in the context of individual clinical circumstances to direct care. All cancer drugs described in the guidelines are funded in accordance with the Outpatient Cancer Drug Benefit Program, at no charge, to eligible residents of Alberta, unless otherwise explicitly stated. For a complete list of funded drugs, specific indications, and approved prescribers, please refer to the Outpatient Cancer Drug Benefit Program Master List.# 
Participation of members of the Alberta Provincial GI Tumour Team in the development of this guideline has been voluntary and the authors have not been remunerated for their contributions. There was no direct industry involvement in the development or dissemination of this guideline. CancerControl Alberta recognizes that although industry support of research, education and other areas is necessary in order to advance patient care, such support may lead to potential conflicts of interest. Some members of the Alberta Provincial GI Tumour Team are involved in research funded by industry or have other such potential conflicts of interest. However the developers of this guideline are satisfied it was developed in an unbiased manner.

# BACKGROUND
Colorectal cancer (CRC) is the second most commonly diagnosed cancer in Canada, and is the second leading cause of cancer deaths in Canadian men and the third leading cause of cancer deaths in Canadian women. 1 There were approximately 27,000 new diagnoses in Canada in 2017 (incidence rate: 79.6 per 100,000 in men, 54.9 per 100,000 in women); Alberta patients with newly diagnosed CRC are most commonly diagnosed with stage III disease, accounting for 28.6% of all new CRC cases in 2018. 2 There were 9,400 deaths associated with CRC in Canada in 2017, and the 5-year overall survival rate is 63% in men and 65% in women. 1 Rates of CRC continue to increase among adults younger than 50 years of age in Canada. 3,4 Surgical resection is the primary treatment for 80% of CRC patients with non-metastatic disease. Despite potentially curative surgery and the use of chemotherapy and/or radiotherapy, more than 40% of stage II/III patients will experience disease recurrence following primary therapy. The majority of recurrences occur within the first five years, predominantly in the liver, but also the lungs in patients with distal rectal tumours; a large (N=83,000) SEER analysis reported 5-year disease-specific conditional survival probability 80% for stage I/II/III CRC patients. 5 The rate of recurrence in years 5-10 may be higher in men (8.3%) than women (5.3%). 6 The optimal surveillance protocol for non-metastatic CRC patients post-treatment remains controversial, in part due to wide variation in surveillance protocols in randomized trials. 7 Variable surveillance strategies have been published from different jurisdictions with no clear consensus, and are summarized in Appendix A.

# GUIDELINE QUESTION
What is the appropriate posttreatment surveillance protocol for adult patients who have completed treatment for stage I, II, or III colorectal cancer?

# DEVELOPMENT AND REVISION HISTORY
This guideline was reviewed and endorsed by the Alberta Gastrointestinal (GI) Tumour Team. Members of the Alberta GI Tumour Team include surgeons, radiation oncologists, medical oncologists, gastroenterologists, nurses, pathologists, and pharmacists. Evidence was selected and reviewed by a working group comprised of members from the Alberta GI Tumour Team, and a Knowledge Management Specialist from the Guideline Resource Unit. 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 Feb. 2008Feb. , and was updated in 2009Feb. , 2010Feb. , 2011Feb. , 2013Feb. , 2014Feb. , and 2019. The 2019 updated expanded the scope to include patients with stage I CRC.

# SEARCH STRATEGY
The original literature search for this guideline spanned from 1990-2008, and included primary literature and guidelines from other jurisdictions. The 2019 update expanded the literature search to July 1, 2018, and included primary literature and guidelines from other jurisdictions. The detailed search criteria and resulting evidence tables can be found in Appendix A.

# TARGET POPULATION
The recommendations outlined in this guideline apply to adults over the age of 18 years who have completed treatment for stage I, II, or III CRC. CEA is an oncofetal protein that is elevated in patients with a variety of cancers including CRC. 9 Elevated preoperative CEA levels should return to baseline postoperatively, if they do not then residual disease should be suspected. 10 In patients with successfully resected primary CRC, the sensitivity and specificity of CEA is dependent on the threshold used. A cutoff value of 2.5 g/mL results in pooled sensitivity of 82% but specificity of 80%; 11 a cutoff value of 10.0 g/mL results in lower sensitivity (68%) but higher specificity (97%), reflecting fewer false positives. Serial measurement of CEA can detect disease recurrence in patients with initially normal CEA levels, although the sensitivity is low (27-50%). 12-15 A postoperative CEA elevation indicates recurrence with relatively high probability, however, normal postoperative CEA levels (even if initially elevated) are not useful in excluding disease recurrence. The use of serial CEA surveillance has been criticized because 30-40% of CRC recurrences are not associated with a measurable elevation in serum CEA. 16 In addition, some studies have failed to show CEA testing improves survival or quality of life, 17,18 and cost-effectiveness has been reported to be relatively poor ($22,963 -$4,888,208 per quality adjusted life year saved). 19 The optimal frequency of CEA measurements during posttreatment surveillance is also unclear, and is largely based on consensus. One study has shown more frequent (every 1-2 months) CEA testing is superior, 20 however others have not. Most published clinical practice guidelines recommend testing every 3-6 months for 3-5 years posttreatment (refer to Appendix B for a complete review).

# SUMMARY OF RECOMMENDATIONS

# Investigation
- CT of the chest, abdomen, and pelvis is recommend at years 1 and 2 posttreatment, with an option for year 3, for all non-metastatic patients who would potentially be considered a candidate for additional treatment.
The primary issue in forming CT recommendations is inconsistent protocols reported in randomized controlled trials. 21 In some cases, CT was performed for only the liver or pelvis, and frequency varied. One meta-analysis did report a survival benefit for CRC patients who received posttreatment CT imaging (every 3-12 months) and frequent CEA measurements, 22 and two others reported a survival benefit associated with liver imaging. 17,23 Other data in support of posttreatment CT surveillance comes from adjuvant chemotherapy trials. While the US Intergroup studies did not mandate CT in the follow-up protocol, two European trials reported that 32% and 44% of relapses were detected by imaging, and 38% and 46% of these patients proceeded to potentially curative resection, respectively. 24,25 The utility of CT imaging should be balanced by concerns about radiation exposure and the risk for second malignancies, particularly in younger patients.
Colonoscopy is recommended at 1 year post-surgery and every 3-5 years thereafter, based on findings, for all non-metastatic patients who would potentially be considered a candidate for additional treatment. Patients with high risk hereditary genetic features (i.e., HNPCC, FAP) may require more frequent colonoscopies, at the discretion of their surgeon or oncologist. 26,27 The primary goal of surveillance colonoscopy is to detect metachronous CRCs, polyps, and anastomotic recurrences of the initial primary to allow for potentially curative treatment. Metachronous lesions develop in 1.5% to 3% of patients in the first 3-5 years postoperatively.  Greater than 50% of these lesions arise within 24 months of the initial resection and may represent synchronous cancers that were missed initially. 28,31,32 Anastomotic recurrences occur in 2% to 4% of patients with colon cancer. Rates are higher in patients with rectal cancer, particularly in patients who did not undergo total mesorectal excision and/or pelvic radiation. 28,33,34 At least 80% of anastomotic recurrences occur within 2.5 years of the primary resection. 31,35 Fecal occult blood testing (FOBT) and/or fecal immunochemical test (FIT) should not be used for surveillance for new primary lesions or polyps.  Meta-analyses of randomized trials have shown that patients who undergo surveillance colonoscopy after CRC resection have higher overall, but non disease-specific survival. 8,40 Neither randomized trials nor meta-analyses have shown a survival benefit in performing colonoscopy at shorter than 3-5 year intervals. 17,28,33,41

# Consider periodic clinical assessment.
Patient history and physical examination (H&P) may be performed at the discretion of the responsible physician. The utility of H&P in this setting is unclear, and there is not strong evidence to suggest that routine H&P increases detection of recurrence or impacts outcomes.

# Patient posttreatment surveillance can be led by their general practitioner (GP), a nurse practitioner, surgeon, or their medical/radiation oncologist.
A randomized trial comparing GP-led vs. surgeon-led surveillance for colon cancer found no difference in patient quality of life, anxiety, depression, or satisfaction, with similar time to recurrence detection, and similar survival rates in each group. 42 A systematic review evaluating which provider patients preferred for CRC posttreatment surveillance found 5 studies that supported specialist-led care, and 9 studies that indicated patient willingness to have follow-up by non-specialist providers (primary care or nursing). 43 7. Information about the late effects of CRC treatment, risk reduction strategies, and health promotion recommendations, should be provided to patients completing treatment, as well as their primary healthcare providers. 27 There is a growing body of literature supporting associations between obesity, physical activity, nutrition, and tobacco use on CRC outcomes such as disease progression, recurrence, and mortality. In Alberta, patients and primary healthcare providers are given resources both at the end of active treatment and when the patients is transferred to their primary healthcare provider, including letters and booklets. These tools facilitate further discussions with the patient and presents an opportunity to improve care coordination by clarifying roles. The After Treatment -Information and Resources to Help You Set Priorities and Take Action booklet and sample letters are accessible on the external website. 

# GLOSSARY OF ABBREVIATIONS
Acronym

# DISSEMINATION
- Present the guideline at the local and provincial tumour team meetings and weekly rounds.
- Post the guideline on the Alberta Health Services website.
- Send an electronic notification of the new guideline to all members of CancerControl Alberta.

# MAINTENANCE
A formal review of the guideline will be conducted at the Annual Provincial Meeting in 2020. If critical new evidence is brought forward before that time, however, the guideline working group members will revise and update the document accordingly. It takes into consideration related information presented at local, national, and international meetings, similar guidelines published by the American Society for Clinical Oncology (ASCO), the National Comprehensive Cancer Network (NCCN), and Cancer Care Ontario (CCO), as well as the Alberta Provincial Gastrointestinal Tumour Team's interpretation of the data.

# Search:
Grey Literature: Guidelines related to CRC surveillance published between January 1, 2013 and July 1, 2018 were identified using Google Advanced Search and the National Guidelines Clearinghouse database.
Results: 9 guidelines from other jurisdictions were identified and included (Table 1). Results: 23 articles found, 13 included: 8 relevant trials (Table 2), 5 systematic reviews/ meta-analyses (Table 3) were identified and included o CEA is insufficiently sensitive to be used alone, even with a low threshold; essential to augment CEA monitoring with another diagnostic modality in order to avoid missed cases o trying to improve sensitivity by adopting a low threshold is a poor strategy because of the high numbers of false alarms generated - Recommendation: monitoring for colorectal cancer recurrence with more than one diagnostic modality but applying the highest CEA cut-off assessed (10 g/L)