Colon Cancer Guidelines

Updated: Dec 01, 2022
  • Author: Tomislav Dragovich, MD, PhD; Chief Editor: N Joseph Espat, MD, MS, FACS  more...
  • Print

Guidelines Summary

Guidelines contributor:  Elwyn C Cabebe, MD Physician Partner, Valley Medical Oncology Consultants; Medical Director of Oncology, Clinical Liason Physician, Cancer Care Committee, Good Samaritan Hospital

Guidelines on colorectal screening have been issued by the following organizations:

  • American Cancer Society (ACS), US Multi-Society Task Force on Colorectal Cancer, and American College of Radiology
  • U.S. Preventive Services Task Force (USPSTF)
  • American College of Physicians (ACP)
  • American College of Gastroenterology (ACG)
  • National Comprehensive Cancer Network (NCCN)
  • European Society for Medical Oncology (ESMO)

While all the guidelines recommend routine screening for colorectal cancer and adenomatous polyps in asymptomatic adults, they differ with regard to frequency of screening and age at which to discontinue screening, as well as the preferred screening method. Although the customary age for starting screening in persons at average risk has been 50 years, the increasing incidence of colorectal cancer in younge people has prompted several organizations to lower the recommended starting age to 45 years. For high-risk patients, the recommendations differ regarding the age at which to begin screening, as well as the frequency and method of screening.

American Cancer Society (ACS), US Multi-Society Task Force on Colorectal Cancer, and American College of Radiology

A joint guideline developed by the American Cancer Society, US Multi-Society Task Force on Colorectal Cancer, and the American College of Radiology, published in 2008, recommends that screening for colorectal cancer and adenomatous polyps start at age 50 years in asymptomatic men and women. [59]

In addition, individuals with any of the following colorectal cancer risk factors should undergo colonoscopy at an earlier age and more frequently than those at average risk:

  • Family history of colorectal cancer or polyps

  • Family history of a hereditary colorectal cancer syndrome such as familial adenomatous polyposis (FAP) or hereditary non-polyposis colon cancer (HNPCC)

  • Personal history of colorectal cancer

  • Personal history of chronic inflammatory bowel disease (ulcerative colitis or Crohn disease)

  • Screening options for average risk adults consist of tests that detect adenomatous polyps and cancer, and tests that primarily detect cancer. Any one of these tests can be used for screening.

Tests that detect adenomatous polyps and cancer, and their recommended frequency, include the following:

  • Flexible sigmoidoscopy every 5 years
  • Colonoscopy every 10 years
  • Double-contrast barium enema every 5 years
  • Computed tomographic (CT) colonography every 5 years

Tests that primarily detect cancer, and their recommended frequency, include the following:

  • Annual guaiac-based fecal occult blood test (FOBT) with high test sensitivity for cancer
  • Annual fecal immunochemical test (FIT) with high test sensitivity for cancer
  • Stool DNA test with high sensitivity for cancer, interval uncertain

American Cancer Society update

In 2018 the ACS revised its colorectal screening guidelines, advising that regular screening for people at average risk start at age 45 years. [155]  Additional ACS recommendations include the following:

  • For people in good health and with a life expectancy of more than 10 years, regular colorectal cancer screening should continue through the age of 75.
  • People ages 76 through 85 should make a decision with their medical provider about whether to continue screening, based on their own personal preferences, life expectancy, overall health, and prior screening history.
  • People over 85 should discontinue colorectal cancer screening.          

U.S. Preventive Services Task Force (USPSTF)

The USPSTF recommends that screening for colorectal cancer start at age 50 years and continue until age 75 years (grade A recommendation) but offers a grade B recommendation for screening adults age 45 to 49 years. For adults aged 76 to 85 years, the decision to screen should be individualized, taking into account the patient’s overall health, prior screening history, and preferences (grade C recommendation). The USPSTF advises that in those older patients, screening is more likely to benefit those who have never been screened than those who have undergone screening, and is more likely to benefit patients who are healthy enough to undergo treatment for colorectal cancer treatment and who do not have other medical conditions limiting their life expectancy. [156]

The USPSTF does not recommend colorectal cancer screening for adults older than 85 years. [156]

The USPSTF notes that colorectal screening is substantially underused. As part of a strategy to increase screening rates, the guidelines provide a range of screening options rather than a ranking of tests.

Stool-based screening tests and intervals are as follows:

  • Guaiac-based fecal occult blood test (FOBT), every year
  • Fecal immunochemical test (FIT), every year
  • FIT-DNA, every 1 to 3 years

Direct visualization screening tests and intervals are as follows:

  • Colonoscopy, every 10 years
  • Computed tomographic (CT) colonography, every 5 years
  • Flexible sigmoidoscopy, every 5 years
  • Flexible sigmoidoscopy with FIT; sigmoidoscopy every 10 years, with FIT every year

American College of Physicians (ACP)

In 2019, the American College of Physicians recommended that average-risk adults aged 50 to 75 years should be screened for colorectal cancer by one of the following strategies [157] :

  • FIT or high-sensitivity FOBT or FIT every 2 years
  • Colonoscopy every 10 years
  • Flexible sigmoidoscopy every 10 years plus FIT every 2 years

Clinicians should discontinue screening for colorectal cancer in average-risk adults older than 75 years or in adults with a life expectancy of 10 years or less. [157]

American College of Gastroenterology (ACG)

American College of Gastroenterology (ACG) 2021 guidelines recommend colorectal cancer screening in average-risk individuals of age 50 to 75 years, and suggest screening in average-risk individuals of age 45 to 49 years. The ACG recommends colonoscopy and FIT as the primary modalities for colorectal cancer screening. [47]  Further ACG suggestions regarding colorectal cancer screening include the following:

  • Initiate colorectal cancer screening with a colonoscopy at age 40 or 10 years before the youngest affected relative, whichever is earlier, in individuals in whom a first-degree relative has had colorectal cancer or an advanced polyp before age 60 years or in whom two or more first-degree relatives have had colorectal cancer or an advanced polyp at any age; perform interval colonoscopy every 5 years.
  • Consider genetic evaluation in individuals with a higher familial colorectal cancer burden (higher number and/or younger age of affected relatives).
  • In individuals in whom a first-degree relative has had colorectal cancer or an advanced polyp at age 60 years or older, initiate colorectal cancer screening at age 40 or 10 years before the youngest affected relative, then resume screening according to average-risk screening recommendations.
  • In individuals with a second-degree relative with colorectal cancer or an advanced polyp, follow average-risk colorectal cancer screening recommendations.
  • Decide whether to continue screening beyond age 75 years on an individualized basis.
  • In individuals unable or unwilling to undergo colonoscopy or FIT, consider screening with flexible sigmoidoscopy, multitarget stool DNA test, CT colonography, or colon capsule.
  • Do not use the Septin 9 methylated DNA test Septin 9 for screening.

The National Comprehensive Cancer Network (NCCN)

The National Comprehensive Cancer Network (NCCN) has released separate guidelines for average-risk and high-risk individuals. [158, 159]  For average individuals, the recommendations are nearly identical to those of the joint American Cancer Society (ACS), US Multi-Society Task Force on Colorectal Cancer, and American College of Radiology. However, in 2021 the NCCN lowered the age for starting screening in average-risk individuals from 50 years to 45 years. [158]

The NCCN guidelines provide screening recommendations for patients at increased risk due to any of the following [158] :

  • Personal history of adenoma or sessile serrated polyp
  • Personal history of colorectal cancer
  • Inflammatory bowel disease
  • Positive family history

The guidelines also specify recommendations for patients with the following high-risk syndromes [159] :

  • Lynch syndrome
  • Familial adenomatous polyposis (FAP)
  • Attenuated familial adenomatous polyposis (AFAP)
  • MUTHYH-associated polyposis
  • Peutz-Jeghers syndrome (PJS)
  • Juvenile polyposis syndrome (JPS)
  • Serrated polyposis syndrome (SPS)
  • No syndrome, but familial risk present

Individuals meeting one or more of the following criteria should receive further evaluation for high-risk syndromes:

  • Individuals meeting the revised Bethesda Guidelines (Lynch Syndrome)
  • Family members meeting Amsterdam criteria (Lynch Syndrome)
  • Individuals with more than 10 adenomas detected ( MUTYH)
  • Individuals with multiple GI hamartomatous polyps (PJS and JPS)
  • Family members with a known high-risk syndrome associated with colorectal cancer, with or without a known mutation
  • Individuals with a desmoid tumor

European Society for Medical Oncology

The ESMO guidelines note that colonoscopic techniques, despite being invasive, have the advantage of being both diagnostic and therapeutic. [160] Recommendations for invasive screening are as follows:

  • A complete colonoscopy is the recommended method for colorectal cancer screening in average-risk men and women. The optimal age range for testing is 50-74 years, with an optimal repetition interval for a negative test of 10 years.

  • Flexible sigmoidoscopy (FS) every 5–10 years may be an alternative for patients who refuse colonoscopy. The combination of FS with a yearly fecal occult blood test (FOBT) is recommended to reduce the risk of a right colon tumor.

  • Other invasive tests, including capsule colonoscopy, are not recommended for screening.

The ESMO guidelines recommend non-colonoscopic tests in average-risk men and women age ≥50 years who are not already taking part in colonoscopic screening programs. The optimal frequency of testing is every year and no later than every 3 years. When the test results are positive, a colonoscopy must be carried out at the earliest convenience. FIT appears to be superior to high-resolution guaiac FOBT with respect to the detection rate and positive predictive value for adenomas and cancer.

For patients with Lynch syndrome, ESMO guidelines recommend colonoscopy every 1-2 years, starting at age 25 years in those with MLH1/MSH2 mutations and at age 35 years in those with MSH6/PMS2 mutations. For patients with FAP, ESMO guidelines recommend sigmoidoscopy every 1-2 years, starting at age 12-15 years; every 1-2 years; if adenomas are found at sigmoidoscopy, colonoscopy should be performed annually until the patient undergoes colectomy. [161]


Familial Risk

Hereditary nonpolyposis colorectal cancer (HNPCC), also known as Lynch syndrome, is a common autosomal dominant syndrome characterized by early age at onset, neoplastic lesions, and microsatellite instability (MSI). Guidelines for Lynch syndrome screening have been developed by the National Cancer Institute (Bethesda guidelines) and the National Comprehensive Cancer Network (NCCN). [97]

The American Gastroenterological Association recommends testing all patients with colorectal cancer for Lynch syndrome; the tumor should be tested for MSI or with immunohistochemistry for MLH1, MSH2, MSH6, and PMS2 proteins. [162]

The European Society for Medical Oncology (ESMO) guidelines for familial risk-colorectal cancer, [163] which have been endorsed by the American Society of Clinical Oncology (ASCO), [164]  includes the following recommendations:

  • Tumor testing for DNA mismatch repair (MMR) deficiency with immunohistochemistry for MMR proteins and/or MSI should be assessed in all patients with colorectal cancer. As an alternate strategy, tumor testing should be carried out in individuals with CRC younger than 70 years, or those older than 70 years who fulfill any of the revised Bethesda guidelines
  • If loss of MLH1/PMS2 protein expression is observed, analysis of BRAF V600E mutation or analysis of methylation of the MLH1 promoter should be conducted to rule out a sporadic case. If tumor is MMR deficient and somatic BRAF mutation is not detected or MLH1 promoter methylation is not identified, testing for germline mutations is indicated.

  • If loss of any of the other proteins (MSH2, MSH6, PMS2) is observed, germline genetic testing should be carried out for the genes corresponding to the absent proteins (eg, MSH2, MSH6, EPCAM, PMS2, or MLH1).

  • Full germline genetic testing for Lynch syndrome should include DNA sequencing and large rearrangement analysis.

The American College of Gastoenterology recommendations are in general agreement with ESMO. [165]  The NCCN guidelines note that although high MSI status or MMR deficiency associated with the BRAF V600E mutation is usually due to epigenetic mechanisms and is not inherited, it does not rule out Lynch syndrome; approximately 1% of cancers with BRAF V600E mutations (and loss of MLH1) are Lynch syndrome. Germline testing  in such patients is recommended if there is a strong family history. [97]

Revised Bethesda guidelines for Lynch syndrome and microsatellite instability

Because cancers with MSI account for approximately 15% of all colorectal cancers, in 1996 the National Cancer Institute developed the Bethesda guidelines for the identification of individuals with HNPCC who should be tested for MSI. These guidelines, which were most recently revised in 2002, recommend testing tumors for MSI in the following situations [48] :

  • Colorectal cancer (CRC) diagnosed in a patient who is younger than 50 years of age
  • Presence of synchronous or metachronous colorectal or other Lynch syndrome–related tumors, regardless of age
  • CRC with MSI-high histology diagnosed in a patient who is younger than 60 years of age
  • CRC diagnosed in a patient with one or more first-degree relatives with a Lynch syndrome–related cancer, with one of the cancers being diagnosed before age 50
  • CRC diagnosed in a patient with two or more first- or second-degree relatives with Lynch syndrome–related cancer, regardless of age

Postpolypectomy Surveillance

A 2020 update of US Multi-Society Task Force on Colorectal Cancer guidelines provides recommendations on postpolypectomy surveillance. The recommendations assume high-quality baseline colonoscopy, defined as meeting all the following criteria [65] :

  • Adequate bowel preparation
  • Performance by a colonoscopist with adequate adenoma detection rate
  • Complete examination to the cecum
  • Attention to complete polyp excision

Screening colonoscopy findings and recommended scheduling of surveillance colonoscopy are as follows [65] :

  • Normal colonoscopy, or  < 20 hyperplastic polyps < 10 mm: 10 years
  • 1–2 adenomas < 10 mm: 7–10 years
  • 3–4 adenomas < 10 mm: 3–5 years
  • 5–10 adenomas, adenoma ≥10 mm, or adenoma with villous component or high-grade dysplasia: 3 years
  • More than 10 adenomas: 1 year, with consideration for genetic testing based on adenoma burden, age, and family history
  • Piecemeal resection of adenoma ≥20 mm: 6 months, then 1 year later, then 3 years after the second examination
  • 1–2 sessile serrated polyps (SSPs) < 10 mm: 5–10 years
  • 3–4 SSPs < 10 mm or hyperplastic polyp ≥10 mm: 3–5 years
  • 5–10 SSPs, SSP ≥10 mm, SSP with dysplasia, or traditional serrated adenoma:  3 years

In 2020, the British Society of Gastroenterology (BSG), the Association of Coloproctology of Great Britain and Ireland (ACPGBI) and Public Health England (PHE) released joint guidelines for surveillance after polypectomy and colorectal cancer resection.  According to the guidelines, the criteria for high-risk for future colorectal cancer (CRC) following polypectomy comprise either of the following [166] :

  • Two or more premalignant polyps, including at least one advanced colorectal polyp (defined as a serrated polyp of at least 10 mm in size or containing any grade of dysplasia, or an adenoma of at least 10 mm in size or containing high-grade dysplasia)  or
  • Five or more premalignant polyps

Patients who meet the high-risk criteria should undergo a single surveillance colonoscopy at 3 years.  Patients who have undergone CRC resection should have a colonoscopy at 1 year post-surgery and every 3 years thereafter. [166]

Patients who do not meet high-risk criteria postpolypectomy should participate in national bowel screening when invited. For patients who are more than 10 years younger than the national bowel screening lower age limit, colonoscopy may be considered after 5 or 10 years and individualized to age and other risk factors. [166]


Familial Adenomatous Polyposis

The European Society of Medical Oncology offers the following recommendations for suveillance of patients with familial adenomatous polyposis (FAP) [163] :

Classic FAP

  • Colon and rectum: Sigmoidoscopy (or colonoscopy) every 1 to 2years, starting at age 10 to 11 years and continued lifelong in mutation carriers. Once adenomas are detected, annual colonoscopy until colectomy. Surgery is indicated if there are large numbers of adenomas, including adenomas showing a high degree of dysplasia.

  • Gastroduodenal adenomas: Gastroduodenal endoscopy starting when colorectal polyposis is diagnosed or at age 25 to 30 years, whichever comes first. Surveillance intervals are based on the Spigelman stage.

  • Thyroid cancer:  Consider annual cervical ultrasonography starting at age 25 to 30 years.

  • Desmoid tumors: Consider baseline computed tomography (CT) or magnetic resonance imaging (MRI) scan in presence of risk factors (positive family history for desmoids and site of the mutation in APC).

Attenuated FAP

  • Colon and rectum: Colonoscopy every 1 to 2 years, starting at age 18 to 20 years and continued lifelong in mutation carriers. Once adenomas are detected, colonoscopy should be carried out annually.

  • Gastroduodenal adenomas: Gastroduodenal endoscopy starting when colorectal polyposis is diagnosed or at age 25 to 30 years, whichever comes first. Surveillance intervals are based on the Spigelman stage.

  • Thyroid cancer: Annual cervical ultrasonography may be consideredstarting at age 25 to 30 years.

  • Desmoid tumors: A baseline CT scan or MRI should be considered if risk factors (positive family history for desmoids and site of the mutation in APC).

The American Society of Colon and Rectal Surgeons recommends that patients with familial adenomatous polyposis (FAP) or with personal or family risk factors for FAP be referred to center registries and genetic counselors with experience in the multidisciplinary management of these individuals. [167]

Additional recommendations include [167] :

  • Prophylactic colectomy or proctocolectomy should be routine; the frequency and type of surgery should depend on the severity of the polyposis phenotype
  • Use of chemoprevention as primary therapy is not recommended
  • Small tubular adenomas with mild dysplasia can be kept under surveillance, but adenomas with severe dysplasia must be removed
  • Duodenectomy or pancreaticoduodenectomy is recommended for persistent or recurrent severe dysplasia in the papilla or duodenal adenomas
  • Clinically inert tumors should be treated with sulindac or not treated at all
  • Slowly growing or mildly symptomatic tumors may be treated with less toxic regimens such as sulindac and tamoxifen or with vinblastine and methotrexate
  • Rapidly growing tumors need aggressive therapy with either very-high-dose tamoxifen or antisarcoma-type chemotherapy
  • Radiation is an option if collateral damage is not a major concern



Surgical Treatment

The American Society of Colon and Rectal Surgeons practice parameters for the management of colon cancer recommend colectomy as the primary treatment for localized resectable colon cancer. [168]

Additional recommendations are as follows:

  • The extent of resection of the colon should correspond to the lymphovascular drainage of the site of the colon cancer; the lymphadenectomy should be complete and en bloc with the bowel segment
  • Clinically positive lymph nodes located outside the standard field of resection that are suspected to contain metastatic disease should be biopsied or removed at the time of primary resection
  • Resection of involved adjacent organs should be en bloc

National Comprehensive Cancer Network (NCCN) guidelines also recommend colectomy, with en bloc removal of regional lymph nodes, for treatment of resectable, nonobstructing colon cancer. [97]  In addition, for clinical T4b disease, neoadjuvant chemotherapy may be considered. The NCCN states that laparoscopic-assisted colectomy may be considered, based upon the following criteria:

  • The surgeon has experience performing laparoscopically assisted colorectal operations
  • No locally advanced disease, acute bowel obstruction, or perforation from cancer is present
  • Thorough abdominal exploration is required
  •  Preoperative marking of small lesions should be considered 

NCCN recommendations for lymphadenectomy are as follows [97] :

  • Lymph nodes at the origin of feeding vessel should be identified for pathologic exam
  • Clinically positive lymph nodes outside the field of resection that are considered suspicious should be biopsied or removed, if possible
  • Positive nodes left behind indicate an incomplete (R2) resection
  • A minimum of 12 lymph nodes need to be examined to establish N stage

European Society for Medical Oncology (ESMO) recommendations for surgical treatment of localized colon cancer include the following [160] :

  • For noninvasive adenocarcinomas (pTis—ie, intraepithelial or intramucosal), en bloc endoscopic resection of the polyp is sufficient.

  • Invasive carcinoma (pT1) in a polyp requires a thorough review with the pathologist and surgeon. High-risk features mandating surgical resection with lymphadenectomy include lymphatic or venous invasion, grade 3 differentiation, and significant (grade >1) tumor budding.

  • Laparoscopic colectomy can be safe when technical expertise is available, in the absence of contraindications.

  • Obstructive colon cancers can be treated in one- or two-stage procedures, as indicated.


Adjuvant and Neoadjuvant Therapy

National Comprehensive Cancer Network (NCCN) guidelines list numerous adjuvant therapy regimens for colon cancer. Regimens for metastatic colon cancer include molecular-targeted agents chosen on the basis of testing for KRAS, NRAS, and BRAF mutations. [97]

NCCN preferred regimens for adjuvant therapy for patients with resected, nonmetastatic colon cancer depend on the stage of disease, as follows:

  • Stage I disease and low-risk stage II disease with high microsatellite instability (MSI-H): No adjuvant therapy required; patients with low-risk stage II disease can be enrolled in a clinical trial, observed without adjuvant therapy, or considered for 6 months of capecitabine or 5-fluorouracil (FU)/leucovorin (LV).
  • High-risk stage II disease: 5-FU/LV, capecitabine, FOLFOX (5-FU, LV, oxaliplatin), or capecitabine/oxaliplatin (CapeOx); observation without adjuvant therapy is also an option
  • Low-risk stage III (pathologic stages T1-3/N1): CapeOx for 3 months or FOLFOX for 3 to 6 months 
  • High-risk stage III disease (pathologic stages T4/N1-2 and anyT/N2): CapeOx for 3 to 6 months or FOLFOX for 6 months

The American Society of Clinical Oncology (ASCO) recommends against the routine use of adjuvant chemotherapy in patients with stage II colon cancer who are at low risk of recurrence, including in younger patients. However, ASCO recommends offering adjuvant chemotherapy to patients with stage IIB colon cancer (ie, T4) and stage IIC colon cancer (ie, lesions either penetrating visceral peritoneum or invasive of surrounding organ), with a discussion of the potential benefits and risks of harm. In addition, ASCO suggests offering adjuvant therapy to patients with stage IIA colon cancer who have any of the following high-risk factors (with consideration of the number of risk factors as part of the shared decision-making process, since the presence of more than one risk factor may increase the risk of recurrence):

  • Sampling of fewer than 12 lymph nodes in the surgical specimen
  • Perineural or lymphovascular invasion
  • Poorly differentiated or undifferentiated tumor grade
  • Intestinal obstruction
  • Tumor perforation
  • Grade BD3 tumor budding (≥ 10 buds)

ASCO guidelines do not routinely recommend the addition of oxaliplatin to fluoropyrimidine-based adjuvant therapy, but consider that it may be offered as a result of shared decision making. ASCO recommends against routinely offering adjuvant therapy to patients with mismatch repair deficiency/microsatellite instability (dMMR/MSI) tumors, but if the combination of dMMR/MSI and high-risk factors results in a decision to offer adjuvant therapy, ASCO recommends including oxaliplatin in the chemotherapy regimen. In patients who are candidates for adjuvant doublet chemotherapy, the duration of adjuvant oxaliplatin-containing chemotherapy may be 3 or 6 months, [77]

European Society for Medical Oncology (ESMO) guidelines for localized colon cancer recommend starting adjuvant chemotherapy as soon as possible after surgery and ideally not later than 8 weeks. ESMO recommendations for adjuvant treatment regimens vary by disease stage and risk category. [160] For stage II disease, recommendations are as follows:

  • Low risk: Follow-up without chemotherapy
  • Intermediate risk (lymphatic, perineural, or vascular invasion; histologic grade 3; tumor obstruction; or preoperative CEA > 5 ng/ml): If MSI, follow-up only; if MSS, de Gramont regimen for 6 months or capecitabine for 6 months
  • High risk (pT4, < 12 lymph nodes, multiple risk factors from intermediate risk group): FOLFOX for 6 months or CapeOx for 3 or 6 months

For adjuvant treatment of stage III colon cancer, ESMO guidelines recommend combinations of fluoropyrimidines—either 5-FU or capecitabine—and oxaliplatin. Dihydropyrimidine dehydrogenase (DPD) genotyping or phenotyping is strongly recommended before initiating fluoropyrimidine-based adjuvant therapy.

  • Low risk (pT1-3, N1): FOLFOX for 6 months or CapeOx for 3 months
  • High risk (pT4 and/or N2): FOLFOX or CapeOx for 6 months

Neoadjuvant Therapy

Guidelines from the American Society of Colon and Rectal Surgeons include the following recommendations on neoadjuvant therapy for colon cancer [168] :

  • In patients with locally advanced colon cancer, neoadjuvant chemotherapy or radiotherapy can result in tumor regression and may facilitate margin-negative excision of locally advanced cancers.
  • In patients with initially resectable colon cancer liver metastasis, an individualized decision should be made on neoadjuvant chemotherapy followed by surgical resection or up-front surgery.
  • Patients with initially unresectable colon cancer liver metastasis should be considered for neoadjuvant chemotherapy to attempt to convert to resectability.
  • Hepatic artery infusion of chemotherapy combined with systemic chemotherapy or immunotherapy may increase resectability of colon cancer liver metastasis, but should be performed only in centers with the appropriate expertise.

For more information on chemotherapy regimens, see Colon Cancer Treatment Protocols.


Follow-up Care in Stage II and III Colorectal Cancer

Guidelines on follow-up care for survivors of stage II and stage III colorectal cancer were issued by the following organizations:

  • Cancer Care Ontario endorsed by American Society of Clinical Oncology (ASCO)
  • European Society for Medical Oncology (ESMO)
  • National Comprehensive Cancer Network (NCCN)
  • American Society of Colon and Rectal Surgeons (ASCRS)

All four guidelines agree that patients with resected colon cancer (stage II and III) should undergo regular surveillance for at least 5 years following resection, and that surveillance should include regular reviews of medical history, physical examination, and carcinoembryonic antigen assays, as well as colonoscopy and abdominal and chest computed tomography (CT [140, 141, 97, 169] The frequency of the surveillance testing differs as shown in the table below.

Table 1. (Open Table in a new window)



ESMO (2013) [141]

ASCO (2013) [140]

NCCN  (2016) [97]

ASCRS (2015) [169]

History and physical exam

Every 3-6 mo for 3 y, then every 6 -12 mo at 4 and 5 y

Every 3-6 mo for 3 y, then every 6 mo to 5 y

Every 3-6 mo for 2 y, then every 6 mo to 5 y

Every 3-6 mo for 2 y, then every 6 mo to 5 y


Every 3-6 mo for 3 y, then every 6 -12 mo at 4 and 5 y

Every 3 mo for 3 y*

Every 3-6 mo for 2 y, then every 6 mo to 5 y

Every 3-6 mo for 2 y, then every 6 mo to 5 y

Chest CT*

Every 6-12 mo for first 3 y

Every 1 y for 3 y

Every 1 y for 5 y

Every 1 y for 5 y


At y 1 after surgery, and every 3-5 y thereafter

At 1 y, then every 5 y, dictated by the findings on the previous colonoscopy

At 1 y, 3 y, and 5 y if negative

At y 1 after surgery, and every 3-5 y dictated by the findings on the first postoperative examination.

Abdominal CT*

Every 6-12 mo for first 3 y

Every 1 y for 3 y

Every 1 y for 5 y; scans to include pelvis

Every 1 y for 5 y

ESMO = European Society of Medical Oncology; ASCO = American Society of Clinical Oncology; NCCN = National Comprehensive Cancer Network; American Society of Colon and Rectal Surgeons = ASCRS CEA = carcinoembryonic antigen; CT = computed tomography * For patients at high risk for recurrence (eg, lymphatic or venous invasion, or poorly differentiated tumors). **Colonoscopy should be performed 3-6 mo postoperatively if preoperative colonoscopy was not done, due to an obstructing lesion; otherwise, colonoscopy in 1 y; if abnormal, repeat in 1 year; if no advanced adenoma (ie, villous polyp, polyp >1 cm, or high-grade dysplasia), repeat in 3 y, then every 5 y.

In 2016, the US Multi-Society Task Force on Colorectal Cancer issued guidelines on colonoscopy after colorectal cancer resection, which included the following recommendations [170] :

  • Patients with colorectal cancer (CRC) should undergo high-quality perioperative clearing with colonoscopy. The procedure should be performed preoperatively, or within a 3- to 6-mo interval after surgery in the case of obstructive CRC. The goals of perioperative clearing colonoscopy are detection of synchronous cancer and detection and complete resection of precancerous polyps.
  • Patients who have undergone curative resection of either colon or rectal cancer should receive their first surveillance colonoscopy 1 yr after surgery (or 1 yr after the clearing perioperative colonoscopy).
  • Patients with localized rectal cancer who have undergone surgery without total mesorectal excision, those who have undergone transanal local excision (ie, transanal excision or transanal endoscopic microsurgery) or endoscopic submucosal dissection, and those with locally advanced rectal cancer who did not receive neoadjuvant chemoradiation and then surgery using total mesorectal excision techniques, are at increased risk for local recurrence. In these situations, it is suggested that patients undergo local surveillance with flexible sigmoidoscopy or endoscopic ultrasound (EUS) every 3−6 mo for the first 2−3 yr after surgery. These surveillance measures are in addition to recommended colonoscopic surveillance for metachronous neoplasia.
  • In patients with obstructive CRC precluding complete colonoscopy, CT colonography (CTC) is recommended as the best alternative to exclude synchronous neoplasms. Double-contrast barium enema is an acceptable alternative if CTC is not available.

Molecular Testing in Metastatic Disease

 In 2015, the American Society for Clinical Pathology (ASCP), the College of American Pathologists (CAP), the Association for Molecular Pathology (AMP), and the American Society of Clinical Oncology (ASCO) issued a provisional clinical opinion regarding gene mutation testing to predict response to anti–epidermal growth factor receptor (EGFR)  monoclonal antibody (MoAb) therapy in patients with metastatic colorectal carcinoma (mCRC). Among the recommendations are the following [171] :

  • RAS mutational testing of colorectal carcinoma tissue should be performed in a Clinical Laboratory Improvement Amendments–certified laboratory for patients who are being considered for anti-EGFR therapy

  • Analysis should include KRAS and NRAS codons 12 and 13 of exon 2; 59 and 61 of exon 3; and 117 and 146 of exon 4.

  • Anti-EGFR MoAb therapy (currently cetuximab and panitumumab) should only be considered for treatment of patients with mCRC who are identified as having tumors with no mutations detected after extended RAS mutation analysis

The 2016 European Society for Medical Oncology (ESMO) guidelines for the management of patients with mCRC concur with the ASCP/CAP/AMP/ASCO RAS mutational testing recommendations above. Additional recommendations include the following [172] :

  • Tumor  BRAF mutation status should be assessed alongside the assessment of tumor  RAS mutational status for prognostic assessment (and/or potential selection for clinical trials)
  • Dihydropyrimidine dehydrogenase (DPD) testing before 5-FU administration remains an option but is not routinely recommended 

  • UGT1A1 phenotyping remains an option and should be carried out in patients with a suspicion of UGT1A1 deficiency as reflected by low conjugated bilirubin and in patients where an irinotecan dose of >180 mg/m2 per administration is planned 

  • TS activity and TSER genotyping are not recommended for use in clinical practice

  • ERCC1 expression for treatment decisions involving the use of oxaliplatin is not recommended outside of clinical trial



Targeted Therapy

For BRAF V600E–mutated colorectal cancer unresponsive to previous oxaliplatin-based therapy without irinotecan, National Comprehensive Cancer Network (NCCN) guidelines include any of the following options for subsequent therapy [97] :

  • Irinotecan plus vemurafenib plus cetuximab or panitumumab (EGFR antibody)
  • Dabrafenib (BRAF inhibitor) plus trametinib (MEK inhibitor) plus cetuximab or panitumumab 
  • Encorafenib (BRAF inhibitor) plus binimetinib (MEK inhibitor) plus cetuximab or panitumumab

Other targeted treatment options are as follows: 

  • Larotrectinib or entrectinib are treatment options for patients with metastatic colorectal cancer that is NTRK gene fusion positive.
  • Combination immunotherapy options for dMMR/MSI-high advanced colorectal cancer are now included. In the first-line setting, nivolumab or pembrolizumab, or a combination of nivolumab and ipilimumab, are listed as category 2B recommendations for patients with dMMR/MSI-high disease who are not appropriate candidates for treatment with cytotoxic combinations.
  • Modified FOLFOXIRI (fluorouracil, leucovorin, oxaliplatin, irinotecan) plus panitumumab or cetuximab is recommended for patients with unresectable metastatic colorectal cancer with synchronous liver and/or lung metastases alone, KRAS/NRAS/BRAF wild-type, and left-sided tumors.