Overview of The Management of Primary Colon Cancer

15/07/2019 Overview of the management of primary colon cancer - UpToDate
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Overview of the management of primary colon cancer

Authors: Miguel A Rodriguez-Bigas, MD, Axel Grothey, MD
Section Editors: Kenneth K Tanabe, MD, Richard M Goldberg, MD
Deputy Editor: Diane MF Savarese, MD
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Jun 2019. | This topic last updated: Jul 11, 2019.
INTRODUCTION
Colorectal cancer is the third most common cancer affecting both males and females in the United
States; approximately 70 percent of cases arise in the colon [1]. Globally, colorectal cancer is the
third most commonly diagnosed cancer in males and the second in females; however, the incidence
varies markedly. Country-specific incidence rates are available through the World Health
Organization (WHO) GLOBOCAN database.
This topic review will provide an overview of the management and prognosis of primary colon
cancer. Epidemiology, risk factors, clinical presentation, and diagnosis are addressed in detail
separately. (See "Colorectal cancer: Epidemiology, risk factors, and protective factors" and "Clinical
presentation, diagnosis, and staging of colorectal cancer".)
DIAGNOSIS
The diagnosis of colon cancer is usually made by colonoscopy. (See "Clinical presentation,
diagnosis, and staging of colorectal cancer".)
STAGING
"Staging" a cancer provides a standard framework for describing disease extent. The stage of a
colon cancer has three components, primary tumor (T), status of the regional nodes (N), and distant
metastasis (M), which together are combined to form stage groupings from I to IV. Stage groupings
permit the stratification of prognosis, which is useful for the selection of treatment. The T, N, and M
categories for colon cancer are assigned based upon:
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● Whether there are signs of cancer spread on physical examination or radiographic imaging
tests
● Findings from surgical resection and histologic examination of the resected tissues
The current combined American Joint Committee on Cancer (AJCC)/Union for International Cancer
Control (UICC) TNM staging for colorectal cancer (eighth edition, 2017) is illustrated in the table
(table 1) [2].
TNM staging for colorectal cancer is discussed in more detail elsewhere, and colon cancer
prognosis, stratified according to stage, is discussed in more detail below. (See "Pathology and
prognostic determinants of colorectal cancer", section on 'TNM staging' and 'Prognosis' below.)
THE CLINICAL STAGING EVALUATION
Pretreatment clinical staging is best accomplished by physical examination (with particular attention
to ascites, hepatomegaly, and lymphadenopathy), computed tomography (CT) scan of the abdomen
and pelvis, and chest imaging. (See "Clinical presentation, diagnosis, and staging of colorectal
cancer", section on 'Clinical staging evaluation'.)
Radiographic imaging — In patients with newly diagnosed invasive colon cancer, preoperative
chest, abdomen, and pelvis CT scans can demonstrate regional tumor extension, regional lymphatic
and distant metastases, and tumor-related complications (eg, obstruction, perforation, fistula
formation), findings that may assist in selecting the therapeutic approach. An important point is that
the finding of isolated liver or lung metastases on preoperative studies may not necessarily alter the
surgical approach to the primary tumor, particularly in patients who are symptomatic from bleeding
or impending obstruction. (See 'Metastatic disease' below and "Locoregional methods for
management and palliation in patients who present with stage IV colorectal cancer", section on
'Management of the primary cancer' and "Surgical resection of primary colon cancer", section on
'Preoperative evaluation'.)
The necessity of preoperative abdominal/pelvic CT for all patients with colon cancer is controversial,
as is the clinical benefit of a staging chest CT. Nevertheless, the standard practice at most
institutions is that all patients with stage II, III, or IV colon cancer undergo chest, abdomen, and
pelvic CT either prior to or following resection, an approach that is endorsed by the National
Comprehensive Cancer Network (NCCN) [3], the American Society of Clinical Oncology (ASCO),
and the European Society for Medical Oncology (ESMO). It is generally preferable to obtain these
scans prior to, rather than after, operation, as the scan results will occasionally change surgical
planning.
Contrast-enhanced magnetic resonance imaging (MRI) of the liver might identify more hepatic
lesions than are visualized by CT and may be indicated to further define the extent of disease in

patients who have suspected liver metastases on CT. (See "Clinical presentation, diagnosis, and
staging of colorectal cancer", section on 'Liver MRI'.)
Positron emission tomography (PET) scans do not appear to add significant information to CT scans
for routine preoperative staging of colon cancer. PET scan may be helpful for patients who are
thought to be candidates for resection of isolated colorectal cancer liver and lung metastases, in
whom the routine use of PET reduces the number of nontherapeutic laparotomies. (See
"Management of potentially resectable colorectal cancer liver metastases", section on 'Utility of PET
scans'.)
Tumor markers — A variety of tumor markers have been associated with colon cancer, especially
carcinoembryonic antigen (CEA). Serum CEA levels should be obtained preoperatively in patients
with colon cancer, particularly as an aid to posttreatment follow-up. Elevated preoperative CEA
levels that do not normalize following surgical resection can imply the presence of persistent
disease and the need for further evaluation. Serum CEA should NOT be used as a screening test
for colon cancer due to low sensitivity and specificity for early stage disease. (See "Clinical
presentation, diagnosis, and staging of colorectal cancer", section on 'Tumor markers'.)
Colonoscopy — Ideally, each patient should have visualization of the entire colon prior to surgery.
Colonoscopy serves to localize the tumor, provide a tissue diagnosis, characterize the lesion as
mucosal or submucosal, and evaluate the patency of the lumen, the presence of extrinsic colonic
compression, and synchronous carcinomas and adenomas. Synchronous invasive colorectal
cancers are found in 3 to 5 percent of cases, while the prevalence of synchronous adenomas is as
high as 30 percent.
If full colonoscopy cannot be performed prior to elective colon resection because of obstruction or
poor preparation, a barium enema, or (preferably) CT or magnetic resonance colonography can be
used to evaluate the entire large bowel. Alternatively, the entire residual colon can be examined
colonoscopically after resection. (See "Clinical presentation, diagnosis, and staging of colorectal
cancer", section on 'Colonoscopy'.)
Family history — A family history of colorectal and other extracolonic cancers (going back three
generations if possible, but at least first- and second-degree relatives) should be sought, as the
patient may be a member of a kindred with a hereditary predisposition. This finding could alter the
surgical approach, prompting consideration of subtotal or total colectomy in high-risk individuals.
(See 'Genetic issues' below and "Lynch syndrome (hereditary nonpolyposis colorectal cancer):
Clinical manifestations and diagnosis" and "MUTYH-associated polyposis", section on 'Colonic
manifestations'.)
However, use of family history alone is not sufficient to identify most patients with a hereditary colon
cancer syndrome, particularly Lynch syndrome. Clinical practice guidelines from ASCO and others
recommend testing of all colorectal cancer for loss of mismatch repair protein expression (the
underlying defect in Lynch syndrome) or microsatellite instability, the biologic footprint of mismatch

repair protein deficiency [4-6]. (See 'Genetic issues' below and "Lynch syndrome (hereditary
nonpolyposis colorectal cancer): Clinical manifestations and diagnosis", section on 'Tumor-based
strategies'.)
MANAGEMENT OF LOCALIZED DISEASE
Surgical resection — Approximately 80 percent of cancers are localized to the colon wall and/or
regional nodes. Surgery is the only curative modality for localized colon cancer. The goal of surgery
for invasive cancer is complete removal of the tumor, the major vascular pedicle, and the lymphatic
drainage basin of the affected colonic segment (figure 1). Surgical procedures for treatment of
primary colon cancer are discussed in detail separately. (See "Surgical resection of primary colon
cancer".)
Restoration of bowel continuity using a primary anastomosis can be accomplished in most patients
undergoing an uncomplicated colectomy. However, a temporary proximal diverting colostomy or
ileostomy may be necessary in cases of diffuse peritonitis or free perforation if the patient is
medically unstable or, sometimes, for an obstructing left-sided colon cancer, although this is
controversial. (See "Surgical resection of primary colon cancer", section on 'Colonic obstruction'.)
Laparoscopic-assisted colectomy, rather than open colectomy, is favored for patients with
nonobstructed, nonperforated, non-locally advanced colon cancers who have not had prior
extensive abdominal surgery. In experienced hands, appropriately selected patients have
comparable oncologic outcomes, comparable perioperative morbidity and mortality, and faster
recovery with laparoscopic as compared with open surgery. (See "Surgical resection of primary
colon cancer".)
There are reports that robotic surgery has been performed safely for colon cancer, but there are no
randomized trials comparing this approach with either laparoscopic or open colonic surgery. (See
"Surgical resection of primary colon cancer".)
Older adult patients — Surgery for colon cancer (including laparoscopic resection [7,8]) should
not be denied simply based on age. A comprehensive geriatric assessment may be useful in
formulating an appropriate, individualized treatment plan for the older adult patient. (See
"Comprehensive geriatric assessment for patients with cancer".)
Specific issues surrounding the use of adjuvant chemotherapy in older adult patients are discussed
elsewhere. (See "Adjuvant therapy for resected colon cancer in elderly patients".)
Management of carcinoma in a polyp — The majority of colon cancers arise from polyps
(adenomas). Benign adenomas, as well as those with severe dysplasia or carcinoma in situ (no
evidence of invasive cancer, defined as invasion into the submucosa), can be effectively managed
by endoscopic removal (polypectomy) alone as long as the resection margins are free of cancer.
Endoscopic resection is also a reasonable alternative to radical surgery for selected favorable-risk
early stage colon cancers arising in a polyp. The presence of any of the following factors should
prompt consideration of radical surgery, as they indicate a higher risk of residual cancer and/or
nodal metastases (see "Surgical resection of primary colon cancer", section on 'Carcinoma in a
polyp'):
● Poorly differentiated histology

● Lymphovascular invasion
● Cancer at the resection or stalk margin
● Invasion into the muscularis propria of the bowel wall (T2 lesion)
● Invasive carcinoma arising in a sessile (flat) polyp with unfavorable features (eg, lower third
submucosal penetration, lymphovascular invasion, poorly differentiated histology)
Locally advanced primary lesions — Multivisceral resection is an appropriate option for locally
advanced (ie, attached to or invading adjacent organs), potentially resectable primary colon
cancers. The surgical approach to locally advanced colon cancer is reviewed separately. (See
"Surgical resection of primary colon cancer", section on 'Locally advanced cancer'.)
Neoadjuvant chemoradiotherapy or chemotherapy — Neoadjuvant (preoperative)

chemoradiotherapy with or without chemotherapy, rather than initial surgery, is a common approach
for locally advanced rectal cancer that is supported by data from randomized trials. (See
"Neoadjuvant chemoradiotherapy, radiotherapy, and chemotherapy for rectal adenocarcinoma".)
There is no consensus as to which patients with colon cancer, if any, are suitable for neoadjuvant
therapy. In our view, patients with potentially resectable disease with negative margins should
undergo resection, rather than upfront chemotherapy or chemoradiotherapy, if they are surgical
candidates. Patients who are appropriate for initial chemotherapy include those with locally
unresectable colon cancer, those whose margins of resection are judged to be potentially
compromised, or those who are medically inoperable. This position is consistent with consensus-
based guidelines from the National Comprehensive Cancer Network (NCCN) [3]. (See "Systemic
chemotherapy for nonoperable metastatic colorectal cancer: Treatment recommendations".)
Until more recently, most of the data addressing the benefit of neoadjuvant therapies in patients with
colon primaries have been limited to isolated case reports and two small case series [9-14]. While
concurrently administered chemotherapy plus radiation therapy (RT) provides synergistic antitumor
activity, it also increases treatment-related toxicity, which may be prohibitive if the radiation
treatment volume includes a substantial amount of bowel.
The utility of preoperative chemotherapy for patients with primary colon cancers was directly
addressed in the phase III FOxTROT trial, in which 1052 patients with a computed tomography (CT)
scan-predicted, T3-4N0-2, nonobstructed primary colon cancer who had no metastatic disease and
who were fit for chemotherapy were randomly assigned to surgery upfront followed by six months of
adjuvant oxaliplatin-based chemotherapy or to six weeks of preoperative oxaliplatin-based
chemotherapy followed by surgery and then 18 additional weeks of chemotherapy [15]. A shorter

duration of chemotherapy (12 weeks) was an option for investigators, but it was only chosen by 6
percent; 72 percent of patients received FOLFOX (oxaliplatin plus short-term infusional fluorouracil
[FU] and leucovorin [LV]) chemotherapy, with the remainder receiving CAPOX (capecitabine plus
oxaliplatin, also called XELOX). In a preliminary report presented at the 2019 annual meeting of the
American Society of Clinical Oncology (ASCO), 75 percent of the enrolled patients had T4 lesions,
or T3 lesions with CT evidence of ≥5 mm of extramural extension. Preoperative chemotherapy was
not associated with higher rates of perioperative complications, including anastomotic leak, but it
was associated with lower rates of incomplete resection (5 versus 10 percent), and histologic
downstaging of both pathologic tumor and nodal stage (including a 4 percent pathologic complete
response rate [pathologic T0]). However, there was only a trend toward lower rates of disease
recurrence at two years, the primary endpoint (13.6 versus 17.2 percent, hazard ratio [HR] for
recurrence 0.75, 95% CI 0.55-1.04). Although fewer patients in the neoadjuvant chemotherapy
group did not receive any chemotherapy (4 versus 27 percent), the majority of the patients who did
not receive chemotherapy in the surgery upfront group did not receive it because they were
perceived to have low-risk disease (16 percent), and only 11 percent either were too unwell for
chemotherapy or refused it.
Adjuvant chemotherapy — For patients who have undergone potentially curative resection of a
colon cancer, the goal of postoperative (adjuvant) chemotherapy is to eradicate micrometastases,
thereby reducing the likelihood of disease recurrence and increasing the cure rate. The benefits of
adjuvant chemotherapy have been most clearly demonstrated in patients with stage III (node-
positive) disease, who have an approximately 30 percent reduction in the risk of disease recurrence
and a 22 to 32 percent reduction in mortality with modern chemotherapy. (See "Adjuvant therapy for
resected stage III (node-positive) colon cancer".)
Most treatments involve a combination of several chemotherapy drugs, which are given
intravenously in a specific order on specific days. For patients with node-positive colon cancer, a
course of oxaliplatin-containing chemotherapy is generally recommended for most patients,
although the benefits of oxaliplatin are controversial in older adults. (See "Adjuvant therapy for
resected colon cancer in elderly patients", section on 'Oxaliplatin-based regimens' and "Adjuvant
therapy for resected stage III (node-positive) colon cancer", section on 'Oxaliplatin-based therapy'.)
The optimal duration of oxaliplatin-containing chemotherapy is evolving. Six months of therapy has
been the standard approach, but the cumulative and dose-limiting neuropathy associated with
oxaliplatin has prompted interest in a shorter duration of therapy. Results from the International
Duration Evaluation of Adjuvant Chemotherapy (IDEA) collaboration (six randomized trials of six
versus three months of oxaliplatin-based adjuvant therapy) suggest that six months of therapy
remains the standard of care for individuals with high-risk cancers (T4 or N2 (table 1)) [16]. On the
other hand, given the small predicted loss of absolute disease-free survival benefit (absolute
difference 0.9 percent at three years) and the significantly lower rates of oxaliplatin neuropathy seen
in the IDEA collaboration analysis, adjuvant therapy can be limited to three months in patients with
low-risk disease (T1-3N1), which makes up approximately 60 percent of all stage III colon cancers.
These data are discussed in more detail separately. (See "Adjuvant therapy for resected stage III
(node-positive) colon cancer", section on 'Oxaliplatin-based therapy'.)
Among patients with resected node-negative (stage II) disease, the benefits of chemotherapy are
controversial, as is the relative benefit of an oxaliplatin-based as compared with a non-oxaliplatin-
based regimen. Treatment decisions must be individualized. Expert guidelines suggest that the risks
and estimated benefits of adjuvant chemotherapy be discussed with patients who have resected
node-negative colon cancer. Among the issues that need to be taken into consideration when
assessing the risk of recurrence and estimated benefit from specific chemotherapy regimens are the
presence of high-risk clinicopathologic features (fewer than 12 nodes in the surgical specimen, T4
stage (table 1), perforated/obstructed tumor, poorly differentiated histology, lymphovascular or
perineural invasion), mismatch repair enzyme status, assessment of comorbidities and anticipated
life expectancy, and given the relatively good prognosis of stage II disease, the potential risks
associated with treatment. If adjuvant chemotherapy is chosen, most patients receive a
fluoropyrimidine alone, unless they have a tumor with deficient mismatch repair status, in which
case adjuvant fluoropyrimidines alone are ineffective. For patients receiving a non-oxaliplatin-based
adjuvant therapy regimen (ie, a fluoropyrimidine alone), six months of adjuvant therapy remains the
standard approach. (See "Adjuvant chemotherapy for resected stage II colon cancer", section on
'Risk stratification' and "Adjuvant chemotherapy for resected stage II colon cancer", section on
'Choice of regimen' and "Adjuvant therapy for resected colon cancer in elderly patients", section on
'Challenges specific to the elderly' and 'Side effects' below.)
Web-based tools are available that can aid the clinician in estimating the risk of recurrence and
death based on clinicopathologic features, comorbidity, and the relative benefits of specific
chemotherapy regimens. Tools such as these can be valuable aids to enhance the decision making
process. However, use of this program is not a substitute for clinical judgment and careful
consideration of all relevant patient- and tumor-related factors that may impact the decision to
pursue adjuvant therapy. (See "Adjuvant chemotherapy for resected stage II colon cancer", section
on 'Web-based tools'.)
In general, older adult patients gain as much benefit from adjuvant FU-based chemotherapy as do
younger individuals, although it is used less often in older adults, and rates of treatment-related
toxicity may be higher. The role of oxaliplatin as a component of adjuvant therapy in older adult
patients is controversial. Specific issues surrounding the use of adjuvant chemotherapy in older
adult patients and the utility of a comprehensive geriatric assessment in formulating an appropriate,
individualized treatment plan for the older adult patient are discussed elsewhere. (See "Adjuvant
therapy for resected colon cancer in elderly patients" and "Comprehensive geriatric assessment".)
Side effects — Chemotherapy carries a risk of significant toxicities, including mucositis, emesis,
diarrhea, febrile neutropenia, fatigue, hair loss, hand-foot syndrome (a condition in which there is
soreness, redness, and peeling of the skin of the palms and soles of the feet), and cardiotoxicity.
The frequency and severity of these side effects vary according to the specific drugs used and how

they are administered. Fortunately, most of these symptoms are reversible with cessation of
chemotherapy, and late and long-term effects are relatively infrequent, with the exception of
oxaliplatin-related peripheral neuropathy, which may persist. In most modern trials, rates of
treatment-related death range from 0.5 to 1 percent. (See "Cutaneous side effects of conventional
chemotherapy agents", section on 'Hand-foot syndrome (acral erythema)' and "Overview of
neurologic complications of platinum-based chemotherapy", section on 'Cumulative sensory
neuropathy' and "Cardiotoxicity of non-anthracycline cancer chemotherapy agents", section on
'Fluorouracil'.)
The most commonly used oxaliplatin-based regimens are FOLFOX and CAPOX. FOLFOX requires
a central venous access catheter and the use of an ambulatory infusion pump. The oxaliplatin
component of CAPOX can be administered via a peripheral vein, but commonly patients require
administration via a central line due to an infusion-related pain syndrome related to oxaliplatin. (See
"Treatment protocols for small and large bowel cancer".)
Patients with stage II disease are more often offered a regimen that does not include oxaliplatin,
typically LV-modulated FU or single-agent oral capecitabine. The range of treatment-related toxicity
can be illustrated by the following clinical trial data:
● In the X-ACT study, severe toxicities associated with six months of adjuvant treatment with oral
capecitabine alone included hand-foot syndrome in 17 percent, diarrhea in 11 percent, nausea
or vomiting in 3 percent, and stomatitis in 2 percent [17]. (See "Cutaneous side effects of
conventional chemotherapy agents", section on 'Hand-foot syndrome (acral erythema)' and
"Adjuvant therapy for resected stage III (node-positive) colon cancer", section on 'Oral
fluoropyrimidines'.)
● In the control arm of the MOSAIC trial, which demonstrated the benefit of oxaliplatin (FOLFOX)
in stage III disease, severe (grade 3 or worse) toxicity with infusional and bolus FU plus LV
consisted of diarrhea (7 percent), neutropenia (5 percent), nausea (2 percent), and stomatitis (2
percent) [18]. Higher rates of diarrhea, nausea/vomiting, and myelosuppression are usually
seen with bolus FU/LV regimens that do not require central venous access or an ambulatory
infusion pump. (See "Adjuvant therapy for resected stage III (node-positive) colon cancer",
section on 'Infusional versus bolus fluorouracil'.)
In the experimental arm of this MOSAIC trial, the addition of oxaliplatin to infusional plus bolus
FU/LV (the FOLFOX regimen) resulted in severe (grade 3 or worse) neutropenia (43 percent),
diarrhea (11 percent), vomiting (6 percent), and stomatitis (3 percent) [18]. In addition, grade 3
sensory neuropathy developed in 13 percent during therapy but was still present at 48 months
in fewer than 1 percent [19].
● The substitution of capecitabine for infusional FU/LV in combination with oxaliplatin increases
the convenience of treatment but tends to be more toxic than FOLFOX. As an example, in one
adjuvant trial, rates of grade 3 or worse toxicity with CAPOX included diarrhea (19 percent),

sensory neuropathy (11 percent), neutropenia (9 percent), vomiting (6 percent), hand-foot

syndrome (5 percent), and dehydration (3 percent) [20]. Rates of severe diarrhea and
dehydration were significantly higher in patients over the age of 65. In contrast, CAPOX was
associated with less severe neutropenia than FOLFOX in all age groups.
Benefit of postoperative radiation therapy — Postoperative RT is not usually considered a

routine component of care for completely resected colon cancer. This is in contrast to patients with
rectal cancer, in whom effective adjuvant therapy for both transmural and node-positive disease
includes RT. Local recurrence is more frequent with rectal cancer due to the local anatomy and the
difficulty in obtaining adequate resection margins. (See "Adjuvant therapy for resected rectal
adenocarcinoma in patients not receiving neoadjuvant therapy", section on 'Introduction'.)
Selected patients with colon cancer who are at high risk for local recurrence (ie, positive resection
margins, perforation or abscess formation, T4 disease (table 1)) might potentially benefit from
adjuvant RT. However, there is a paucity of high-quality evidence addressing the role of adjuvant RT
(with or without concurrent chemotherapy) in patients with resected locally advanced colon cancer.
A single randomized trial failed to show benefit but was closed prior to achieving its accrual goal
because of slow accrual.
Despite the lack of evidence proving benefit from randomized trials, consensus-based guidelines
from NCCN [3] suggest that adjuvant RT be "considered" for patients with T4 disease with
penetration to a fixed structure. Others suggest that RT be considered on a case-by-case basis for
positive resection margins and disease complicated by perforation or abscess formation. This topic
is addressed in detail separately. (See "Adjuvant therapy for resected stage III (node-positive) colon
cancer", section on 'Adjuvant radiation therapy'.)
Adjunctive therapies — The benefits of diet and exercise, aspirin and other nonsteroidal
antiinflammatory drugs (NSAIDS), vitamin D, and coffee consumption on cancer outcomes are
discussed separately. (See "Adjunctive therapy for patients with resected early stage colorectal
cancer: Diet, exercise, NSAIDs, and vitamin D".)
Management in resource-constrained settings — There are few data to guide the treatment
strategy for localized colorectal cancer in resource-constrained settings. ASCO has developed
consensus-based guidelines for early detection and treatment of early stage (localized) colorectal
cancer that stratify recommendations based on the available level of services (basic, limited,
enhanced, and maximal (table 2)) [21,22].
METASTATIC DISEASE
Approximately 20 percent of newly diagnosed colon cancers are metastatic at presentation

(synchronous metastasis). The most common distant metastatic sites are the liver, lungs, lymph

nodes, and peritoneum. (See "Clinical presentation, diagnosis, and staging of colorectal cancer",
section on 'Metastatic disease'.)
Although major advances in systemic chemotherapy have expanded the therapeutic options for
these patients and improved median survival from less than one year in the single-agent
fluoropyrimidine era to more than 30 months, fewer than 20 percent [23] of those treated with
chemotherapy alone are still alive at five years, and only a few are free of disease, unless resection
or ablation of metastases has been performed. (See "Systemic chemotherapy for metastatic
colorectal cancer: General principles", section on 'Chemotherapy versus supportive care' and
"Systemic chemotherapy for metastatic colorectal cancer: General principles".)
On the other hand, surgery provides a potentially curative option for selected patients with limited
metastatic disease, predominantly in the liver and lung. Long-term survival can be achieved with
metastasectomy in as many as 50 percent of cases, and an aggressive surgical approach to both
the primary and the metastatic sites is warranted in conjunction with systemic chemotherapy.
However, even after complete resection of metastases, most patients who are alive at five years are
alive with active disease; only approximately 20 to 30 percent remain free of recurrence long term
and may be cured. The timing of surgical intervention (particularly in patients who present with
synchronous metastatic disease) is controversial. Management of potentially resectable hepatic
metastases (including a discussion as to integration of systemic chemotherapy into the surgical
paradigm) and resection of pulmonary metastases are discussed in detail separately. (See
"Management of potentially resectable colorectal cancer liver metastases" and "Surgical resection of
pulmonary metastases: Outcomes by histology" and "Surgical resection of pulmonary metastases:
Benefits, indications, preoperative evaluation, and techniques".)
Even patients who are not candidates for a curative resection can benefit from surgical palliation for
symptoms of obstruction and bleeding from the primary tumor, although the overwhelming majority
of patients without symptoms who initiate chemotherapy never require palliative surgery [24]. (See
"Locoregional methods for management and palliation in patients who present with stage IV
colorectal cancer".)
PROGNOSIS
The various prognostic factors for patients with resected colon cancer are discussed in detail
separately, but issues related to general prognosis will be briefly reviewed here. (See "Pathology
and prognostic determinants of colorectal cancer", section on 'Prognostic determinants'.)
The most important indicator of outcome following resection of colon cancer is the pathologic stage
at presentation [25,26]. Five-year survival rates according to tumor stage at diagnosis for patients
with colon cancer, derived from the population-based Surveillance, Epidemiology, and End Results
(SEER) database and stratified according to the current 2010 American Joint Committee on Cancer
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(AJCC)/Union for International Cancer Control (UICC) tumor, node, metastasis (TNM) staging
classification, are illustrated in the figure (figure 2) [25].
For individual patients, a postoperative nomogram has been developed that permits prediction of
the risk of a colon cancer recurrence based upon clinicopathologic factors and whether adjuvant
chemotherapy was administered or not [27]. The nomogram, which has not yet been independently
validated, is available online. It is one of two prognostic tools approved for use in patients with colon
cancer by the AJCC, meeting all quality criteria [28].
In addition, an online calculator based upon data from the large ACCENT database is available for
stage III colon cancer that allows the clinician to calculate the estimated risk of disease recurrence
and mortality based upon an individual patient's clinicopathologic features and the relative benefit to
be gained by different adjuvant chemotherapy strategies. The ACCENT-based web calculator is
approved for use in predicting prognosis for patients with colon cancer by the AJCC, meeting all
quality criteria [28]. The derivation and clinical use of this and other tools are discussed in detail
separately. (See "Adjuvant therapy for resected stage III (node-positive) colon cancer", section on
'Web-based tools' and "Adjuvant chemotherapy for resected stage II colon cancer", section on
'Web-based tools'.)
Most of the available prognostic estimates use five-year survival as the endpoint given that most
recurrences develop within this time frame. In data derived from the 20,800-patient ACCENT
database of patients undergoing adjuvant chemotherapy for stage II or III colon cancer, recurrence
rates after five years never exceeded 1.5 percent annually, and after eight years, they were 0.5
percent per year [29].
As a result, conditional survival (eg, the survival probability after a given length of survival) improves
dramatically after five years. As examples:
● In a study of over 83,000 colon cancer survivors derived from the SEER database, as the time
alive increased to five years after diagnosis, the five-year disease-specific conditional survival
probability was ≥80 percent for all disease stages except stage IV (48 percent) [30].
● Late recurrences may develop more often in men. In an analysis of 3622 patients with colon
cancer derived from two French digestive cancer registries, among men with no recurrence five
years after the diagnosis of colon cancer, 1 in 12 (8.3 percent) developed a subsequent
recurrence between years 5 and 10; the corresponding rate for women was 1 in 19 (5.3
percent) [31].
A web-based tool is available to determine conditional survival expectancy based upon initial stage
at diagnosis, ethnicity, age, gender, and histologic grade.
Prognosis for patients with advanced (metastatic) colorectal cancer is highly variable and dependent
on many factors, including age and performance status, site and number of metastases, molecular
factors such as RAS or BRAF mutations and deficient DNA mismatch repair/microsatellite instability

(MSI), eligibility for surgery or additional chemotherapy, and tumor location. Nomograms for overall
and progression-free survival based on several of these clinicopathologic factors have been
developed that can assist in aiding prognostication and patient-physician communication; however,
they do not include tumor location or MSI status and only apply to patients who are not candidates
for or do not undergo metastasectomy [32].
POSTTREATMENT SURVEILLANCE
Following treatment for a stage II or III colon cancer, posttreatment surveillance usually consists of
periodic history and physical examination, with serial assay of the serum concentrations of the
tumor marker carcinoembryonic antigen (CEA), annual surveillance computed tomography (CT)
scans, and colonoscopy to detect metachronous primaries. Guidelines are available from several
groups and are compared and contrasted in the table (table 3). Whether or not posttreatment
surveillance is needed after resection of a stage I colon cancer is controversial, and the guidelines
differ on this point (table 3). However, most recommend only periodic history and physical
examination and colonoscopy. The rationale for and evidence supporting these guidelines are
discussed elsewhere, as are issues that arise in long-term survivors of colon cancer. (See
"Surveillance after colorectal cancer resection" and "Approach to the long-term survivor of colorectal
cancer".)
GENETIC ISSUES
Although most colorectal cancers are sporadic, specific genetic disorders have been identified, most
of which are autosomal dominant, that are associated with a very high risk of developing the
disease. Familial adenomatous polyposis (FAP; 90 percent risk of colorectal cancer by the age of 45
in the absence of prophylactic colectomy) and Lynch syndrome (hereditary nonpolyposis colorectal
cancer [HNPCC]; lifetime risk of colorectal cancer 25 to 75 percent) are the most common of the
familial colorectal cancer syndromes, but together these two conditions account for fewer than 5
percent of cases. (See "Colorectal cancer: Epidemiology, risk factors, and protective factors",
section on 'Hereditary CRC syndromes' and "Clinical manifestations and diagnosis of familial
adenomatous polyposis" and "Lynch syndrome (hereditary nonpolyposis colorectal cancer): Clinical
manifestations and diagnosis".)
Lynch syndrome is more common than FAP and accounts for approximately 2 to 3 percent of all
colonic adenocarcinomas. The term "Lynch syndrome" is now commonly used for families who have
been genetically determined to have a disease-causing defect (inherited or de novo) in one of the
mismatch repair (MMR) genes. The biologic footprint of a defect in MMR capacity is microsatellite
instability (MSI), detected by polymerase chain reaction. Testing of all colorectal cancers is routinely
used to help establish the diagnosis of Lynch syndrome. Some institutions perform MSI testing
and/or immunohistochemistry (IHC) testing for MMR proteins (which are absent when a disease-

causing genetic defect is present) in colorectal cancers in young patients (diagnosed prior to age 50
years) or in those who meet the Bethesda criteria (table 4). However, increasingly, universal testing
of all colorectal cancers for MSI or loss of MMR proteins by IHC is performed, a practice that is
supported by guidelines from the American Society of Clinical Oncology (ASCO), the European
Society for Medical Oncology (ESMO), and the United States Multi-Society Task Force on
Colorectal Cancer [4-6]:
● Absence of MSI and intact expression of all four MMR proteins on IHC rules out Lynch
syndrome.
● Although over 90 percent of Lynch syndrome-related colorectal cancers will demonstrate MSI,
15 percent of sporadic colorectal cancers also have MSI. Thus, the finding of MSI in a
colorectal cancer does not indicate Lynch syndrome but, instead, identifies those patients who
should be referred for additional testing (IHC or germline mutational testing).
● For individuals with evidence of high MSI (MSI-H) or loss of expression of an MMR protein by
IHC, further evaluation is based on the MSI/IHC results and is outlined in the suggested
algorithm (algorithm 1):
• Absence of protein expression of MLH1 and PMS2, MLH1 alone, or PMS2 alone (which is
rare) may be associated with either sporadic or inherited disease. If these proteins are not
expressed in a tumor, the next step is analysis of BRAF V600E mutation or analysis of
methylation of the MLH1 promoter. The presence of a BRAF mutation suggests sporadic
rather than inherited disease, and there is no need to refer for genetic testing. If there is
methylation of the MLH1 promoter and no BRAF mutation, then a disease-causing genetic
defect should be considered, as 5 to 10 percent of these patients may harbor a germline
mutation [33,34].
• On the other hand, loss of expression of MSH2 alone, MSH2 in combination with MSH6, or
MSH6 alone is highly specific for a disease-causing germline defect, and referral for
genetic testing (for the genes corresponding to the absent proteins) is appropriate. (See
"Lynch syndrome (hereditary nonpolyposis colorectal cancer): Clinical manifestations and
diagnosis" and "Lynch syndrome (hereditary nonpolyposis colorectal cancer): Cancer
screening and management".)
Extracolonic cancers are very common in Lynch syndrome, particularly endometrial carcinomas,
which may occur in up to 60 percent of female mutation carriers in some families. Other sites at
increased risk of neoplasm formation include the ovaries, stomach, small bowel, hepatobiliary
system, brain, renal pelvis or ureter, and sebaceous neoplasms of the skin, such as sebaceous
adenomas or carcinomas. Periodic screening is recommended by expert groups. (See "Lynch
syndrome (hereditary nonpolyposis colorectal cancer): Cancer screening and management", section
on 'General measures'.)

The development of one or more of these cancers in a family member of a colon cancer survivor
may prompt consideration for genetic testing. Family history is seldom updated regularly during
follow-up. However, regularly updating a three-generation family history pedigree from cancer
survivors can be valuable to help determine the potential risk of cancer in family members, as well
as the survivor's own risk of subsequent cancers that may be associated with a previously
unrecognized hereditary syndrome.
MANAGEMENT OF LOCALLY RECURRENT DISEASE
Selected patients with locally recurrent colon cancer can be cured, typically with multimodality
therapy. Prognostic factors for outcome in patients with recurrent colon cancer were addressed in a
large database series of 17,381 patients who were enrolled in 18 randomized phase III trials testing
adjuvant chemotherapy for stage II or III colon cancer conducted mainly before 2000 in the era
when treatment was mainly limited to fluorouracil (FU) [35]. The median survival of all patients
experiencing a recurrence was 13 months. Survival was significantly better in patients with initial
stage II rather than stage III tumors (median 18 versus 13 months), in those with a longer disease-
free interval, and in those who did not receive FU-based adjuvant chemotherapy following resection
of the primary tumor.
Although there are no prospective trials to guide therapy, the management of these patients is
typically multidisciplinary and may include chemotherapy, chemoradiotherapy, or intraoperative
radiation therapy in addition to surgery. While guidelines from the National Comprehensive Cancer
Network (NCCN) [3] recommend six months of adjuvant chemotherapy after resection of colorectal
cancer liver metastases, they do not address the utility of chemotherapy after resection of a local
recurrence. The decision must be individualized and is based in part on whether adjuvant therapy
(particularly an oxaliplatin-containing regimen) was administered previously. (See "Management of
potentially resectable colorectal cancer liver metastases", section on 'Systemic chemotherapy'.)
SOCIETY GUIDELINE LINKS
Links to society and government-sponsored guidelines from selected countries and regions around
the world are provided separately. (See "Society guideline links: Colorectal cancer".)
INFORMATION FOR PATIENTS
UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics."
The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading
level, and they answer the four or five key questions a patient might have about a given condition.
These articles are best for patients who want a general overview and who prefer short, easy-to-read
materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more
detailed. These articles are written at the 10th to 12th grade reading level and are best for patients
who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or
e-mail these topics to your patients. (You can also locate patient education articles on a variety of
subjects by searching on "patient info" and the keyword(s) of interest.)
● Basics topics (see "Patient education: Colon and rectal cancer (The Basics)" and "Patient
education: Colectomy (The Basics)")
● Beyond the Basics topics (see "Patient education: Colon and rectal cancer (Beyond the
Basics)" and "Patient education: Colorectal cancer treatment; metastatic cancer (Beyond the
Basics)")
SUMMARY AND RECOMMENDATIONS
● The diagnosis of colon cancer is usually made by colonoscopy. (See 'Diagnosis' above.)
● The combined American Joint Committee on Cancer (AJCC)/Union for International Cancer
Control (UICC) eighth edition tumor, node, metastasis (TNM) staging for colorectal cancer is
illustrated in the table (table 1). (See 'Staging' above.)
● Pretreatment clinical staging is best accomplished by physical examination and computed

tomography (CT) scan of the chest, abdomen, and pelvis. Serum levels of the tumor marker
carcinoembryonic antigen (CEA) should be obtained preoperatively in most patients. (See
'Radiographic imaging' above and 'Tumor markers' above.)
● Ideally, each patient should have a colonoscopic examination of the entire colon prior to
surgery. If full colonoscopy cannot be performed because of obstruction or poor preparation, CT
or magnetic resonance colonography can be done, or alternatively, the entire residual colon
should be examined colonoscopically soon after resection. (See 'Colonoscopy' above.)
● A family history of colorectal and other extracolonic cancers should be sought prior to therapy,
as an inherited predisposition to colon cancer may alter the surgical approach, prompting
consideration of subtotal or total colectomy in high-risk individuals. (See 'Family history' above.)
● Surgical resection is the only curative modality for localized colon cancer. Endoscopic resection
is a reasonable alternative to radical surgery for selected early stage colon cancers arising in a
polyp, as long as they meet certain criteria for favorable risk. (See 'Surgical resection' above
and 'Management of carcinoma in a polyp' above.)
There is no consensus as to which patients, if any, are suitable for neoadjuvant approaches
rather than upfront surgery. In our view, patients with potentially resectable disease with
negative margins should undergo resection, rather than upfront chemotherapy or

chemoradiotherapy, if they are surgical candidates. Patients who are appropriate for initial
chemotherapy include those with locally unresectable colon cancer, those whose margins of
resection are judged to be potentially compromised, or those who are medically inoperable.
(See 'Neoadjuvant chemoradiotherapy or chemotherapy' above.)
● For patients who have undergone potentially curative resection of a colon cancer, postoperative
(adjuvant) chemotherapy eradicates micrometastases, reduces the likelihood of disease
recurrence, and increases cure rates. The benefits have been most clearly demonstrated in
patients with stage III (node-positive) disease. In this setting, a six-month course of oxaliplatin-
based chemotherapy is generally recommended. The benefit of chemotherapy for resected
stage II disease is controversial, and treatment decisions must be individualized. (See 'Adjuvant
chemotherapy' above.)
● Chemotherapy carries a risk of significant toxicities, including mucositis, emesis, diarrhea,

febrile neutropenia, fatigue, hair loss, hand-foot syndrome, and cardiotoxicity. The frequency
and severity of these side effects vary according to the specific drugs used and how they are
administered. Fortunately, most are reversible when chemotherapy is discontinued. (See 'Side
effects' above.)
● Most patients who present with metastatic disease are not surgical candidates, and palliative
chemotherapy is generally recommended. However, surgery may provide a potentially curative
option for selected patients with limited metastatic disease, predominantly in the liver and lung.
An aggressive surgical approach to both the primary and the metastatic sites is warranted in
such patients in conjunction with systemic chemotherapy. For patients with unresectable distant
metastases, the overwhelming majority of patients without symptoms who initiate
chemotherapy never require palliative surgery. (See 'Metastatic disease' above.)
● The most important indicator of outcome following resection of colon cancer is pathologic stage
(figure 2) (see 'Prognosis' above). Following treatment for a stage II or III colon cancer,
posttreatment surveillance usually consists of periodic history and physical examination and
assay of the serum CEA, annual surveillance CT scans, and periodic colonoscopy.
Recommendations for posttreatment surveillance from a number of expert groups are
compared and contrasted in the table (table 3).
● Following treatment for stage I colorectal cancer, posttreatment surveillance consists only of
periodic history and physical examination and colonoscopy. (See 'Posttreatment surveillance'
above.)
● Regularly updating a three-generation family history pedigree from cancer survivors can be
valuable to help determine the potential risk of cancer in family members, as well as the
survivor's own risk of subsequent cancers that may be associated with a previously
unrecognized hereditary syndrome. (See 'Genetic issues' above.)

● Selected patients with locally recurrent colon cancer can be cured, typically with multimodality
therapy. (See 'Management of locally recurrent disease' above.)
Use of UpToDate is subject to the Subscription and License Agreement.
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5. Giardiello FM, Allen JI, Axilbund JE, et al. Guidelines on genetic evaluation and management
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6. Balmaña J, Balaguer F, Cervantes A, et al. Familial risk-colorectal cancer: ESMO Clinical

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7. Chautard J, Alves A, Zalinski S, et al. Laparoscopic colorectal surgery in elderly patients: a

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11. Mizukami H, Yoshizawa Y, Sasaya S, et al. [A case of advanced colon cancer invading the
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12. Cukier M, Smith AJ, Milot L, et al. Neoadjuvant chemoradiotherapy and multivisceral resection
for primary locally advanced adherent colon cancer: a single institution experience. Eur J Surg
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13. Taylor WE, Donohue JH, Gunderson LL, et al. The Mayo Clinic experience with multimodality
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14. Takenami T, Tsujinaka S, Takahashi J, et al. Efficacy of Neoadjuvant Chemotherapy with

Capecitabine plus Oxaliplatin in the Treatment of Locally Advanced Sigmoid Colon Cancer
Invading the Urinary Bladder: A Report of Three Cases. Case Rep Surg 2019; 2019:8129358.
15. Seymour MT, Morton D, et al. FOxTROT: an international randomised controlled trial in 1052 p
atients (pts) evaluating neoadjuvant chemotherapy (NAC) for colon cancer (abstract). J Clin O
ncol 37, 2019 (suppl; abstr 3504). Abstract available online at https://meetinglibrary.asco.org/r
ecord/171160/abstract (Accessed on June 27, 2019).
16. Grothey A, Sobrero AF, Shields AF, et al. Duration of Adjuvant Chemotherapy for Stage III
Colon Cancer. N Engl J Med 2018; 378:1177.
17. Twelves C, Wong A, Nowacki MP, et al. Capecitabine as adjuvant treatment for stage III colon
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18. André T, Boni C, Mounedji-Boudiaf L, et al. Oxaliplatin, fluorouracil, and leucovorin as adjuvant
treatment for colon cancer. N Engl J Med 2004; 350:2343.
19. André T, Boni C, Navarro M, et al. Improved overall survival with oxaliplatin, fluorouracil, and
leucovorin as adjuvant treatment in stage II or III colon cancer in the MOSAIC trial. J Clin
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20. Schmoll HJ, Cartwright T, Tabernero J, et al. Phase III trial of capecitabine plus oxaliplatin as
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Colorectal Cancer: ASCO Resource-Stratified Guideline. J Glob Oncol 2019; 5:1.
22. Lopes G, Stern MC, Temin S, et al. Early Detection for Colorectal Cancer: ASCO Resource-
Stratified Guideline. J Glob Oncol 2019; 5:1.
23. Heinemann V, von Weikersthal LF, Decker T, et al. FOLFIRI plus cetuximab versus FOLFIRI
plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer (FIRE-

3): a randomised, open-label, phase 3 trial. Lancet Oncol 2014; 15:1065.
24. Poultsides GA, Servais EL, Saltz LB, et al. Outcome of primary tumor in patients with
synchronous stage IV colorectal cancer receiving combination chemotherapy without surgery
as initial treatment. J Clin Oncol 2009; 27:3379.
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Byrd, DR, Compton, CC, et al (Eds) (Eds), Springer, New York 2010. p.143.
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27. Weiser MR, Landmann RG, Kattan MW, et al. Individualized prediction of colon cancer
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ual, 8th, Amin MB (Ed), AJCC, Chicago 2017. p.251.
29. Sargent D, Sobrero A, Grothey A, et al. Evidence for cure by adjuvant therapy in colon cancer:
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Topic 2507 Version 58.0

GRAPHICS
Colorectal cancer TNM staging AJCC UICC 8th edition
Primary tumor (T)

T category T criteria
TX Primary tumor cannot be assessed
T0 No evidence of primary tumor
Tis Carcinoma in situ, intramucosal carcinoma (involvement of lamina propria with no

extension through muscularis mucosae)
T1 Tumor invades the submucosa (through the muscularis mucosa but not into the
muscularis propria)
T2 Tumor invades the muscularis propria
T3 Tumor invades through the muscularis propria into pericolorectal tissues
T4 Tumor invades* the visceral peritoneum or invades or adheres ¶ to adjacent organ or

structure
T4a Tumor invades* through the visceral peritoneum (including gross perforation of the
bowel through tumor and continuous invasion of tumor through areas of inflammation
to the surface of the visceral peritoneum)
T4b Tumor directly invades* or adheres ¶ to adjacent organs or structures
* Direct invasion in T4 includes invasion of other organs or other segments of the colorectum as a result of direct
extension through the serosa, as confirmed on microscopic examination (for example, invasion of the sigmoid colon
by a carcinoma of the cecum) or, for cancers in a retroperitoneal or subperitoneal location, direct invasion of other
organs or structures by virtue of extension beyond the muscularis propria (ie, respectively, a tumor on the
posterior wall of the descending colon invading the left kidney or lateral abdominal wall; or a mid or distal rectal
cancer with invasion of prostate, seminal vesicles, cervix, or vagina).
¶ Tumor that is adherent to other organs or structures, grossly, is classified cT4b. However, if no tumor is present
in the adhesion, microscopically, the classification should be pT1-4a depending on the anatomical depth of wall
invasion. The V and L classification should be used to identify the presence or absence of vascular or lymphatic
invasion whereas the PN prognostic factor should be used for perineural invasion.
Regional lymph nodes (N)

N category N criteria
NX Regional lymph nodes cannot be assessed
N0 No regional lymph node metastasis
N1 One to three regional lymph nodes are positive (tumor in lymph nodes measuring ≥0.2
mm), or any number of tumor deposits are present and all identifiable lymph nodes are
negative
N1a One regional lymph node is positive
N1b Two or three regional lymph nodes are positive
N1c No regional lymph nodes are positive, but there are tumor deposits in the:
Subserosa
Mesentery
Nonperitonealized pericolic, or perirectal/mesorectal tissues
N2 Four or more regional nodes are positive
N2a Four to six regional lymph nodes are positive
N2b Seven or more regional lymph nodes are positive
Distant metastasis (M)

M category M criteria
M0 No distant metastasis by imaging, etc; no evidence of tumor in distant sites or organs.

(This category is not assigned by pathologists.)
M1 Metastasis to one or more distant sites or organs or peritoneal metastasis is identified

M1a Metastasis to one site or organ is identified without peritoneal metastasis
M1b Metastasis to two or more sites or organs is identified without peritoneal metastasis
M1c Metastasis to the peritoneal surface is identified alone or with other site or organ
metastases
Prognostic stage groups

When T is... And N is... And M is... Then the stage group
is...
Tis N0 M0 0
T1, T2 N0 M0 I
T3 N0 M0 IIA
T4a N0 M0 IIB
T4b N0 M0 IIC
T1-T2 N1/N1c M0 IIIA
T1 N2a M0 IIIA
T3-T4a N1/N1c M0 IIIB
T2-T3 N2a M0 IIIB
T1-T2 N2b M0 IIIB
T4a N2a M0 IIIC
T3-T4a N2b M0 IIIC
T4b N1-N2 M0 IIIC
Any T Any N M1a IVA
Any T Any N M1b IVB
Any T Any N M1c IVC
TNM: tumor, node, metastasis; AJCC: American Joint Committee on Cancer; UICC: Union for International Cancer Control.
Used with permission of the American College of Surgeons, Chicago, Illinois. The original source for this information is the
AJCC Cancer Staging Manual, Eighth Edition (2017) published by Springer International Publishing. Corrected at 4th
printing, 2018.
Graphic 111438 Version 6.0

Arterial circulation to the large bowel
IMA: inferior mesenteric artery; SMA: superior mesenteric artery.

American Society of Clinical Oncology (ASCO) framework of resource

stratification [1,2]
Setting Description
Basic Core resources or fundamental services are absolutely necessary for any public
health/primary health care system to function; basic-level services typically are applied in a
single clinical interaction.
Limited Second-tier resources or services are intended to produce major improvements in outcome,
such as incidence and cost effectiveness, and are attainable with limited financial means and
modest infrastructure; limited-level services may involve single or multiple interactions.
Universal public health interventions are feasible for a greater percentage of the population
than the primary target group.
Enhanced Third-tier resources or services are optional but important; enhanced-level resources should
produce further improvements in outcome and increase the number and quality of options
and individual choice (perhaps ability to track patients and links to registries).
Maximal* May use high-resource-setting guidelines.
High-level/state-of-the-art resources or services may be used or are available in some high-

resource countries and/or may be recommended by high-resource-setting guidelines that do
not adapt to resource constraints, but that nonetheless should be considered a lower priority
than those resources or services listed in the other categories on the basis of extreme cost
and/or impracticality for broad use in a resource-limited environment.
* To be useful, maximal-level resources typically depend on the existence and functionality of all lower-level resources.
References:
1. Anderson BO, Shyyan R, Eniu A, et al. Breast cancer in limited-resource countries: An overview of the Breast Health
Global Initiative 2005 guidelines. Breast J 2006; 12:S3.
2. Horton S, Gauvreau CL. Cancer in low- and middle-income countries: An economic overview. In: Cancer: Disease
Control Priorities, 3rd ed, Gelband H, Jha P, Sankaranarayanan R, et al (Eds), The International Bank for
Reconstruction and Development/The World Bank, Washington, DC 2015.
From: Costas-Chavarri A, Nandakumar G, Temin S, et al. Treatment of Patients With Early-Stage Colorectal Cancer: ASCO
Resource-Stratified Guideline. J Glob Oncol 2019; 5:1. Available at: http://ascopubs.org/doi/10.1200/JGO.18.00214.
Copyright © 2019 Costas-Chavarri A, Nandakumar G, Temin S, et al. Reproduced under the terms of the Creative Commons
Attribution License 4.0.

Observed survival rates for 28,491 cases with adenocarcinoma of

the colon
Data from the SEER 1973 to 2005 Public Use File diagnosed in years 1998 to 2000. Stage I
includes 7417; Stage IIA, 9956; Stage IIB, 997; Stage IIC, 725; Stage IIIA, 868; Stage IIIB,
1492; Stage IIIC, 2000; and Stage IV, 5036.
SEER: Surveillance, Epidemiology, and End Results.
Used with the permission of the American Joint Committee on Cancer (AJCC), Chicago, Illinois. The
original source for this material is the AJCC Cancer Staging Manual, Seventh Edition (2010) published
by Springer New York, Inc.

Summary of professional guidelines regarding posttreatment surveillance for

resected colon and rectal cancer
History and
CEA Endoscopic
Organization physical CT scanning Comments
testing surveillance
examination
ASCO [1] and Every 3 to 6 Every 3 to 6 Abdomen and Colonoscopy at 1 Posttreatment

CCO [2] months for 5 months for 5 chest annually year*; subsequent surveillance strategy
years. years. for 3 years; studies dictated by guided by the estimated
pelvis: rectal prior findings. If risk of recurrence and
cancer only, negative, every 5 functional status. These
annually for 3 to years. recommendations are
5 years. Proctosigmoidoscopy for resected stage II
every 6 months for and III colon and rectal
2 to 5 years if rectal cancer.
cancer and no pelvic Recommendations not
RT. provided for resected
stage I or IV disease
due to lack of data to
guide recommendation.
American Cancer Every 3 to 6 Every 3 to 6 Abdomen/pelvis Colonoscopy in year High-risk stage I/II
Society [8] months for the months for and chest every 1; if advanced disease not defined.
first 2 years, then the first 2 12 months for 5 adenoma, repeat
every 6 years, then years for stage in 1 year; otherwise,
months to 5 years. every 6 III and high- repeat in 3 years. If
months to 5 risk stage I/II no advanced
years if the disease. adenoma in year 4,
patient is a repeat every 5
potential years.
candidate for
further
intervention.
NCCN [3] Every 3 to 6 Every 3 to 6 Colon: Colonoscopy at 1 Recommendations apply

months for 2 months for 2 Abdomen/pelvis year ¶; subsequent to stage II, III, and
years, then every years for and chest every studies dictated by resected stage IV colon
6 months for 3 ≥T2 disease, 6 to 12 prior findings. If no cancer, and for stage I,
years. then every 6 months for up advanced adenoma, II, III, or resected stage
months for 3 to 5 years for repeat at 3 years, IV rectal cancer.
years. For those at high then every 5 years;
resected risk of if advanced
metastatic recurrence ¥. For adenoma at 1 year,
disease, rectal cancer, CT repeat at 1 year.
every 3 to 6 chest/abdomen Flexible
months for 2 and pelvis every sigmoidoscopy with
years, then 3 to 6 months EUS or MRI every 3
every 6 for 2 years, then to 6 months for 2
months for 3 every 6 to 12 years, then every 6
to 5 years. months for up months to
to 5 years for complete 5 years for
those at high patients with rectal
risk of cancer undergoing
recurrence ¥. For transanal excision
resected only.
metastatic
disease, CT
abdomen/pelvis
and chest every
3 to 6 months
for 2 years, then
every 6 to 12
months up to

a total of 5
years.
ESMO colon Every 3 to 6 Every 3 to 6 Abdomen and Colonoscopy at 1 Guidelines are for
cancer [4] months for 3 months for 3 chest every 6 to year; every 3 to 5 localized colon cancer;
years, then every years, then 12 months for 3 years thereafter. do not state if
6 to 12 months for every 6 to 12 years; CEUS can applicable to resected
2 years. months for 2 substitute for stage I disease. CTs
years. abdominal CT. recommended for
patients at "higher" risk
of recurrence.
ESMO rectal Every 6 months Every 6 A minimum of 2 Colonoscopy every 5 High-risk patients (eg,
cancer [5] for 2 years Δ. months for CT scans of the years up to age 75. circumferential
the first 3 chest, abdomen, resection margin
years. and pelvis in the positive) may merit
first 3 years. more proactive
surveillance for local
recurrence.
New Zealand [6] Clinical For high-risk All individuals Colonoscopy at 1 Recommendations cover
assessment ◊ cancer with stages I to year §; colonoscopy stages I, II, and III
stratified (stage IIB, III colorectal every 6 to 12 colorectal cancer.
according to risk III): Every 6 cancer should months for 3 years
of recurrence: to 12 months have liver for high-risk patients
High-risk for 3 years, imaging (stages IIB, III),
cancer then between years 1 then annually for at
(stage IIB, annually for and 3. least 5 years.
III): Every 6 2 years. For low-risk
to 12 months For lower patients,
for 3 years, risk (stage I, colonoscopy every 3
then IIA), or with to 5 years. For rectal
annually for comorbidities cancer, proctoscopy
2 years. restricting or sigmoidoscopy at
Lower risk future 3, 6, 12, and 24
(stage I, surgery: months postsurgery;
IIA), or with Annually for colonoscopy at 3- to
comorbidities 5 years. 5-year intervals
restricting thereafter.
future
surgery:
Annual
review for 5
years or
when
symptoms
occur.
US Multi-Society Colonoscopy 1 year

Task Force on after surgery (or 1
Colorectal year after the
Cancer [9] clearing
perioperative
colonoscopy). The
interval to the next
colonoscopy should
be 3 years and
then 5 years. If
neoplastic polyps
are detected, the
intervals between
colonoscopies should
be shorter and in
accordance with
published guidelines
for polyp
surveillance
[10]
intervals [10]. These
intervals do not
apply to patients
with Lynch
syndrome.
For rectal cancer,
flexible
sigmoidoscopy or
EUS every 3 to 6
months for the first
2 to 3 years after
surgery for patients
at high risk for local
recurrence (refer
to text).
British Columbia Every 3 to 6 Every 3 Liver ultrasound Colonoscopy at 1 These guidelines are for
Medical months for 2 months for 3 or CT scans year; if normal, resected stage II and
Association [7] years, then every years, then (preferred) repeat 3 years later III colon and rectal
6 months for 3 every 6 every 6 months and, if normal, every cancer. Patients with
years. months for 2 for 3 years, then 5 years thereafter. significant
years. annually for 2 comorbidities, very
years. Annual advanced age, or
chest CT for 3 limited 5-year life
years. expectancy are not
routinely offered
surveillance.
CEA: carcinoembryonic antigen; CT: computed tomography; ASCO: American Society of Clinical Oncology; CCO: Cancer
Care Ontario; RT: radiation therapy; NCCN: National Comprehensive Cancer Network; EUS: endoscopic ultrasound; MRI:
magnetic resonance imaging; ESMO: European Society for Medical Oncology; CEUS: contrast-enhanced transabdominal
ultrasound.
* Except if no preoperative colonoscopy because of obstructing lesion; do as soon as possible after completion of adjuvant
chemotherapy rather than waiting until 1 year.
¶ Except if no preoperative colonoscopy because of obstructing lesion; recommend at 3 to 6 months rather than waiting
until 1 year.
Δ Minimum provisional recommendation.
◊ Clinical assessment for patients with colon cancer includes physical examination, CEA, chest/abdominal and pelvic CT
scans, colonoscopy, and liver ultrasound. Clinical assessment for rectal cancer patients includes physical examination, CEA,
chest/abdominal and pelvic CT scans, colonoscopy, and proctoscopy or sigmoidoscopy.
§ If no complete colonoscopy before surgery, perform colonoscopy within 6 months.
¥ Features suggesting a high risk of recurrence: poorly differentiated histology, lymphatic or venous invasion.
References:
1. Meyerhardt JA, Mangu PB, Flynn PJ, et al. Follow-Up Care, Surveillance Protocol, and Secondary Prevention Measures
for Survivors of Colorectal Cancer: American Society of Clinical Oncology Clinical Practice Guideline Endorsement. J
Clin Oncol 2013; 31:4465.
2. Cancer Care Ontario. www.cancercare.on.ca.
3. National Comprehensive Cancer Network. Available at: www.nccn.org.
4. Labianca R, Nordlinger B, Beretta GD, et al. Early colon cancer: ESMO Clinical Practice Guidelines for diagnosis,
treatment and follow-up. Ann Oncol 2013; 24 Suppl 6:vi64.
5. Glynne-Jones R, Wyrwicz L, Tiret E, et al. Rectal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment
and follow-up. Ann Oncol 2017; 28 (suppl 4):iv22.
6. Guidance on Surveillance for People at Increased Risk of Colorectal Cancer. Published by the New Zealand Guidelines
Group for the Ministry of Health PO Box 10 665, Wellington 6143, New Zealand. Available at:
http://www.health.govt.nz/publication/guidance-surveillance-people-increased-risk-colorectal-cancer.
7. British Columbia Medial Association. Follow-up of Colorectal Polyps or Cancer (2013).
http://www.bcguidelines.ca/pdf/colorectal_followup.pdf.
8. American Cancer Society Colorectal Cancer Survivorship Care Guidelines. CA Cancer J Clin 2015; 65:427.
9. Colonoscopy surveillance after colorectal cancer resection: Recommendations of the US Multi-Society Task Force on
Colorectal Cancer (American Gastroenterological Association, American College of Gastroenterology, American
Society for Gastrointestinal Endoscopy). Gastroenterology 2016; 150:758.
10. Guidelines for colonoscopy surveillance after screening and polypectomy from the US Multi-Society Task Force on
Colorectal Cancer. Gastroenterology 20121; 143:844.

The revised Bethesda guidelines for testing colorectal tumors for microsatellite
instability (MSI)
Tumors from individuals should be tested for MSI in the following situations:
1. Colorectal cancer diagnosed in a patient who is less than 50 years of age.
2. Presence of synchronous, metachronous colorectal, or other HNPCC-associated tumors *, regardless of age.
3. Colorectal cancer with the MSI-H ¶-like histology Δ diagnosed in a patient who is less than 60 years of age ◊.
4. Colorectal cancer diagnosed in a patient with one or more first-degree relatives with an HNPCC-related tumor, with
one of the cancers being diagnosed under age 50 years.
5. Colorectal cancer diagnosed in a patient with two or more first- or second-degree relatives with HNPCC-related
tumors, regardless of age.
HNPCC: hereditary nonpolyposis colorectal cancer; MSI-H: microsatellite instability-high.

* HNPCC-related tumors include colorectal, endometrial, stomach, ovarian, pancreas, ureter and renal pelvis, biliary tract,
and brain (usually glioblastoma as seen in Turcot syndrome) tumors, sebaceous gland adenomas and keratocanthomas in
Muir-Torre syndrome, and carcinoma of the small bowel.
¶ MSI-H in tumors refers to changes in two or more of the five National Cancer Institute-recommended panels of
microsatellite markers.
Δ Presence of tumor infiltrating lymphocytes. Crohn's-like lymphocytic reaction, mucinous/signet-ring differentiation, or
medullary growth pattern.
◊ There was no consensus among the Workshop participants on whether to include the age criteria in guideline 3 above;
participants voted to keep less than 60 years of age in the guidelines.
Reproduced with permission from Umar A, et al. J Natl Cancer Inst 2004; 96:261. Copyright © 2004 Oxford University
Press.

Testing algorithm for Lynch syndrome
MSI: microsatellite instability; IHC: immunohistochemistry; MSI-L: low MSI; MSS: microsatellite stable; MSI-H: high
MSI; MMR: mismatch repair.
* Proceeding with MLH1 methylation studies and BRAF v600E mutation analysis on tumor before germline genetic
testing can be considered, particularly if the individual does not meet revised Bethesda guidelines.
Reproduced with permission from: Goodenberger M, Lindor NM. Lynch syndrome and MYH-associated polyposis:
review and testing strategy. J Clin Gastroenterol 2011; 45:488. Copyright © 2011 Lippincott Williams & Wilkins.

Contributor Disclosures
Miguel A Rodriguez-Bigas, MD Consultant/Advisory Boards: Astra Zeneca [Gastrointestinal (colorectal)
oncology (Durvalumab)]. Axel Grothey, MD Nothing to disclose Kenneth K Tanabe,
MD Grant/Research/Clinical Trial Support: Enanta Pharmaceuticals [Liver fibrosis (EDP2305, EDP2191,
EDP6556, EDP7750, EDP5513, EDP2294, EDP6591, EDP6856, EDP7315, EDP3533, EDP4297)]; Zafgen
Pharmaceuticals [Hepatocellular carcinoma (ZGN-1345, ZGN-1136)]. Consultant/Advisory Boards: Best
Doctors [GI cancers, melanoma (Medical care)]; Cancer Expert Now [GI cancers, melanoma (Medical care)];
Advanced Medical [GI cancers, melanoma (Medical care)]; Leidos [Melanoma, GI cancers (Grant application
review for the Congressionally Directed Medical Research Program)]. Patent Holder: EGF SNP to determine
risk for HCC [Cirrhosis, hepatocellular carcinoma]; Use of EGFR inhibitors to prevent HCC [Cirrhosis,
hepatocellular carcinoma]. Equity Ownership/Stock Options: Helix12 [Breast cancer (Company owns IP on
selective estrogen receptor modulators for breast cancer)]. Richard M Goldberg, MD Grant/Research/Clinical
Trial Support: Merck [Colon cancer (Pembrolizumab)]. Consultant/Advisory Boards: EMD Serono [Drug
development (Multiple experimental agents)]; Taiho [Drug development (TAS 102)]; Merck [GI cancers
(Pembrolizumab)]; Merck KGA [GI cancers (Multiple experimental agents)]; Novartis [new drug development],
Amgen [paid lecture and travel]. Diane MF Savarese, MD Nothing to disclose
Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are
addressed by vetting through a multi-level review process, and through requirements for references to be
provided to support the content. Appropriately referenced content is required of all authors and must conform to
UpToDate standards of evidence.
Conflict of interest policy

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Official reprint from UpToDate®

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THE CLINICAL STAGING EVALUATION

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MANAGEMENT OF LOCALIZED DISEASE

● Poorly differentiated histology

Neoadjuvant chemoradiotherapy or chemotherapy — Neoadjuvant (preoperative)

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sensory neuropathy (11 percent), neutropenia (9 percent), vomiting (6 percent), hand-foot

Benefit of postoperative radiation therapy — Postoperative RT is not usually considered a

Approximately 20 percent of newly diagnosed colon cancers are metastatic at presentation

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MANAGEMENT OF LOCALLY RECURRENT DISEASE

SOCIETY GUIDELINE LINKS

INFORMATION FOR PATIENTS

SUMMARY AND RECOMMENDATIONS

● Pretreatment clinical staging is best accomplished by physical examination and computed

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● Chemotherapy carries a risk of significant toxicities, including mucositis, emesis, diarrhea,

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Use of UpToDate is subject to the Subscription and License Agreement.

6. Balmaña J, Balaguer F, Cervantes A, et al. Familial risk-colorectal cancer: ESMO Clinical

7. Chautard J, Alves A, Zalinski S, et al. Laparoscopic colorectal surgery in elderly patients: a

9. Yoh T, Yamamichi K, Oishi M, et al. [A case of effective neoadjuvant chemoradiotherapy with

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14. Takenami T, Tsujinaka S, Takahashi J, et al. Efficacy of Neoadjuvant Chemotherapy with

21. Costas-Chavarri A, Nandakumar G, Temin S, et al. Treatment of Patients With Early-Stage

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3): a randomised, open-label, phase 3 trial. Lancet Oncol 2014; 15:1065.

Topic 2507 Version 58.0

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Colorectal cancer TNM staging AJCC UICC 8th edition

Primary tumor (T)

TX Primary tumor cannot be assessed

T0 No evidence of primary tumor

Tis Carcinoma in situ, intramucosal carcinoma (involvement of lamina propria with no

T2 Tumor invades the muscularis propria

T3 Tumor invades through the muscularis propria into pericolorectal tissues

T4 Tumor invades* the visceral peritoneum or invades or adheres ¶ to adjacent organ or

T4b Tumor directly invades* or adheres ¶ to adjacent organs or structures

Regional lymph nodes (N)

NX Regional lymph nodes cannot be assessed

N0 No regional lymph node metastasis

N1a One regional lymph node is positive

N1b Two or three regional lymph nodes are positive

N2 Four or more regional nodes are positive

N2a Four to six regional lymph nodes are positive

N2b Seven or more regional lymph nodes are positive

Distant metastasis (M)

M0 No distant metastasis by imaging, etc; no evidence of tumor in distant sites or organs.