2/1/2018 Rectal Cancer Workup: Laboratory Studies, Screening for Colon and Rectal Cancer, Histologic Findings

Rectal Cancer Workup

Updated: Jan 30, 2018
Author: Burt Cagir, MD, FACS; Chief Editor: N Joseph Espat, MD, MS, FACS more...

WORKUP

Laboratory Studies
Routine laboratory studies should include a complete blood count (CBC); serum chemistries,
including liver and renal function tests; and a carcinoembryonic antigen (CEA) test. A cancer
antigen (CA) 19-9 assay, if available, may also be useful to monitor the disease.

Screening CBC may demonstrate a hypochromic, microcytic anemia, suggesting iron deficiency.
The combined presence of vitamin B-12 or folate deficiency may result in a normocytic or
macrocytic anemia. All men and postmenopausal women with iron deficiency anemia require a GI
evaluation.

Liver function tests are usually part of the preoperative workup. The results are often normal, even
in patients with metastases to the liver.

Perform a CEA test in all patients with rectal cancer. A baseline level is obtained before surgery
and a follow-up level is obtained after surgery. If a previously normalized CEA begins to rise in the
postoperative period, this suggests possible recurrence. A CEA level higher than 100 ng/mL
usually indicates metastatic disease and warrants a thorough investigation. The steps of the
workup are outlined in Figure 1.

Diagnostics. Staging and workup of rectal cancer patients.

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Fecal immunochemical tests appear to be accurate for detecting colorectal cancer. In a meta-
analysis that examined 8 different brands of fecal immunochemical tests (FITs), Lee and
colleagues found that FITs had high accuracy, high specificity, and moderately high sensitivity for
the detection of colorectal cancers. [28, 29] The meta-analysis, which included 19 studies with
sample sizes ranging from 80 to 27,860, showed that FITs had sensitivity of 0.79, specificity of
0.94, a positive likelihood ratio of 13.10, and a negative likelihood ratio of 0.23. The overall
diagnostic accuracy of FITs was 95%.

Screening for Colon and Rectal Cancer

The process of malignant transformation from adenoma to carcinoma takes several years. The
purpose of screening is to eradicate potential cancers while they are still in the benign stage of the
adenoma-carcinoma sequence. Screening also increases the likelihood of discovering existing
cancers while they are still in the early stage.

Screening techniques
Screening techniques include the following:

Guaiac-based fecal occult blood test (FOBT): Perform FOBT yearly by testing 2 samples
from each of 3 consecutive stools. If any of the 6 sample findings is positive, recommend that
the patient have the entire colon studied via colonoscopy or flexible sigmoidoscopy. FOBT
has significant false-positive and false-negative rates.
Stool DNA screening (SDNA): SDNA screening is done using polymerase chain reaction of
sloughed mucosal cells in stool. This test evaluates for genetic alterations that lead to the
cancer formation. Compared with no testing, SDNA testing is cost effective and has high
sensitivity for invasive cancer.
Fecal immunochemical test (FIT): Fecal immunochemical testing uses a monoclonal antibody
assay to identify human hemoglobin. This test is more specific for lower GI tract lesions. The
presence of the globin molecule is indicative of bleeding in the colon and rectum because the
globin molecule is broken down during passage through the upper GI tract. This test is
probably the wave of the future in fecal occult blood testing and may serve as screening in
certain populations. FIT has comparable sensitivity for the detection of proximal and distal
advanced neoplasia. [30]
Rigid proctoscopy: Rigid proctosigmoidoscopy can be performed without an anesthetic,
allows direct visualization of the lesion, and provides an estimation of the size of the lesion
and degree of obstruction. This procedure is used to obtain biopsies of the lesion, assess
ulceration, and determine the degree of fixation. The rigid proctoscopy is proven to be a
highly reproducible method of determining the level of rectal cancer and does not depend on
the operator and on the technique. Therefore, it gives an accurate measurement of the
distance of the lesion from the anal verge; the latter is critical in deciding which operation is
appropriate. The anal verge should be used as preferred landmark because the lowest edge
of the rectal cancer and the anal verge can be visualized simultaneously during rigid
proctoscopy evaluation. In conclusion, the level of rectal cancer must be confirmed by rigid
proctoscopy. [31]
Flexible sigmoidoscopy (FSIG): Perform this test every 5 years. Biopsy any lesions identified,
and perform a full colonoscopy. With flexible sigmoidoscopy, lesions beyond the reach of the
sigmoidoscope may be missed. FSIG introduces significant variability for the level of rectal
cancer and level of rectum itself. Therefore, FSIG should not be used to determine the level
of the rectal cancer. [31] Screening with flexible sigmoidoscopy is associated with significant
decreases in the incidence of colorectal cancer (in both the distal and proximal colon) and in
colorectal cancer mortality (distal colon only). [32]
Combined glucose-based FOBT and flexible sigmoidoscopy: Theoretically, the combination
of these two tests may overcome the limitations of each test.
Double-contrast barium enema (DCBE): Although barium enema is the traditional diagnostic
test for colonic polyps and cancer, the United States Preventive Services Task Force
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(USPSTF) did not consider barium enema in its 2008 update of colorectal cancer screening
recommendations. The USPSTF noted that barium enema has substantially lower sensitivity
than modern test strategies and has not been studied in trials of screening trials; its use as a
screening test for colorectal cancer is declining. [33]
CT colonography (CTC): Virtual colonoscopy (CTC) was introduced in 1994. After bowel
preparation, the thin-cut axial colonic images are gathered in both prone and supine positions
with high-speed helical CT scanner. Then, the images are reconstituted into a 3-dimensional
replica of the entire colon and rectum. This provides a good visualization of the entire colon,
including the antegrade and retrograde views of the flexures and haustral folds. Because this
is a diagnostic study, patients with positive findings should undergo colonoscopic evaluation
the same day.
Fiberoptic flexible colonoscopy (FFC): FFC is recommended every 5-10 years. Colonoscopy
allows full visualization of the colon and excision and biopsy of any lesions. The likelihood is
extremely low that a new lesion could develop and progress to malignancy between
examinations.

Average-risk screening
People who are asymptomatic, younger than 50 years, and have no other risk factors are
considered at average risk for developing colorectal cancer. Screening of the average-risk
population should begin at age 50 years and end at age 75 years. [33] Indications for screening in
patients at average risk for colon and rectal cancer include the following:

No symptoms and age 50-75 years

No symptoms, but requesting screening
Change in bowel habits
Rectal and anal bleeding
Unclear abdominal pain
Unclear iron-deficiency anemia

A French study found that even in patients with no personal or family history of colorectal polyps or
cancer, starting colonoscopy screening at age 45 instead of age 50 can be valuable. In a
prospective study that included 6027 consecutive screening colonoscopies, Karsenti et al found
that for the 515 patients age 45 to 49 years, the average polyp detection rate was 26% and the
average neoplasia detection rate was nearly 4%. By comparison, for the 4438 patients older than
50 years, the average polyp detection rate exceeded 35% and the average neoplasia detection
rate exceeded 5%. Both rates were markedly lower in the 1076 study patients age 44 years and
younger. [34]

The US Multi-Society Task Force on Colorectal Cancer (USMSTF) has endorsed various cost-
effective screening regimens. Screening options for the detection of adenomatous polyps and
cancer for asymptomatic adults 50 years and older include FSIG every 5 years, colonoscopy every
10 years, DCBE every 5 years, or CTC every 5 years. Testing options that primarily detect cancer
in asymptomatic adults 50 years and older include annual glucose-based FOBT with high-test
sensitivity for cancer; annual FIT with high-test sensitivity for cancer; or SDNA with high-test
sensitivity for cancer, although the optimal interval for SDNA is uncertain.

Each screening test has unique advantages. They have been shown to be cost-effective and have
associated risks and limitations. Ultimately, patient preferences and availability of testing resources
guide the selection of screening tests.

The main disadvantage of the structural tests is their requirement for bowel preparation. The
primary advantage of structural tests is that they can detect polyps as well as cancer. Conscious
sedation is usually used for colonoscopy. FSIG is uncomfortable, and screening benefit is limited to
sigmoid colon and rectum. Risks for colonoscopy, DCBE, and CTC may rarely include perforation;
colonoscopy may also be associated with bleeding. Positive findings on FSIG, DCBE, and CTC
usually result in referral for colonoscopy.
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The advantages of the stool tests are that they are noninvasive, do not require bowel preparation,
can be done in the privacy of the patient's home, and are more readily available to patients without
adequate insurance coverage or local resources.

In the United States, colon and rectal cancer screening rates have been averaging between 50%
and 60%. Brounts and colleagues studied colorectal cancer screening in the Military Healthcare
System. In this study, overall screening rates were lower in minority groups than in whites. Also,
overall lower screening rates were identified in patients younger than 65 years. Although ethnicity-
related, gender-related, and age-related disparities were observed, screening rates were improved
in this equal-access health care system when compared with national averages. [35]

Screening of high-risk patients

A patient's family history or personal history may indicate increased risk for colorectal cancer.
Patients at high risk for colon and rectal cancer due to family history who should be included in
surveillance programs include those with the following:

Family history of colon and rectal cancer

First-degree relative with adenoma aged younger than 60 years
Genetic cancer syndromes
Hereditary nonpolyposis colorectal cancer (HNPCC)
Familial adenomatous polyposis (FAP)

Patients at high risk for colon and rectal cancer due to personal history who should be included in
surveillance programs includes the following:

Personal history of inflammatory bowel disease (IBD)

Personal history of adenomas
Personal history of colon or rectal cancer

Screening recommendations by risk factor are as follows:

First-degree relative affected: Offer family members the same screening tests as the general
population; however, begin the screening at age 40 years rather than age 50 years. These
people often undergo colonoscopy as their initial screening test, particularly if the relative was
diagnosed with cancer at a young age.
Family history of FAP: Genetic counseling and genetic testing are recommended to
determine whether the person is a gene carrier. Current tests are approximately 80%
accurate. In the remaining 20%, the mutation cannot be identified. Genetic testing is useful
only if the test result is positive or if the test is a true negative (ie, mutation present in other
family members are not identified in the patient being tested). Flexible sigmoidoscopy should
be offered to known gene carriers and persons with an indeterminate carrier status every
year to look for polyps. When polyposis develops, consider colectomy.
Family history of HNPCC: Genetic counseling and genetic testing should be offered to
individuals whose family histories meet the Amsterdam criteria (see Causes, above). Patients
with documented HNPCC should undergo colonoscopy every 1-2 years when 20-40 years of
age and every year when older than 40 years. Since these cancers tend to be located on the
right side of the colon, flexible sigmoidoscopy is not recommended.
Personal history of adenomatous polyps: Patients who have adenomatous polyps removed
during colonoscopy should have a repeat examination at 1 to 3 years. If the findings of this
examination are normal, follow up at 5 years.
Personal history of colorectal cancer: Patients who have colorectal cancer and undergo
resection for cure should have a repeat colonoscopy after 1 year. If this examination reveals
no abnormalities, follow up at 3 years. In the absence of disease, perform colonoscopy every
5 years thereafter.
Personal history of IBD: Surveillance colonoscopy is performed to look for dysplasia as a
marker for colorectal cancer in patients with long-standing IBD. These patients should
undergo colonoscopy every 1-2 years after 8 years of diffuse disease or after 15 years of
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localized disease. Random biopsies are performed at specific intervals throughout the colon
and rectum. Colectomy is recommended when dysplasia is present.

Histologic Findings
Histopathologic features such as poor differentiation, lymphovascular and/or perineural invasion,
T4 tumor stage, and clinical findings such as obstruction or perforation, and elevated preoperative
CEA levels are all associated with increased recurrence rates and worse survival. [36]

Staging
Dukes Classification
In 1932, Cuthbert E. Dukes, a pathologist at St. Mark Hospital in England, introduced a staging
system for rectal cancer. His system divided tumor classification into three stages, as follows:

Those limited to the rectal wall (Dukes A)

Those that extended through the rectal wall into extra-rectal tissue (Dukes B)
Those with metastases to regional lymph nodes (Dukes C).

This system was modified by others to include subdivisions of stages B and C, as follows:

Stage B was divided into B1 (ie, tumor penetration into muscularis propria) and B2 (ie, tumor
penetration through muscularis propria).

Stage C was divided into C1 (ie, tumor limited to the rectal wall with nodal involvement) and C2 (ie,
tumor penetrating through the rectal wall with nodal involvement).

Stage D was added to indicate distant metastases

Tumor, Node, Metastasis (TNM) System

This system was introduced in 1954 by the American Joint Committee on Cancer (AJCC) and the
International Union Against Cancer (IUAC). The TNM system is a universal staging system for all
solid cancers that is based on clinical and pathologic information. Each category is independent.

Neither the Dukes nor the TNM system includes prognostic information such as histologic grade,
vascular or perineural invasion, or tumor DNA ploidy. TNM staging of rectal cancer correlates well
with 5-year survival rates of patients with rectal cancer (see the TNM stage-dependent 5-year
survival rate for rectal carcinomas).

TNM classification for cancer of the colon and rectum (AJCC)

Primary tumor (T) includes the following:

TX - Primary tumor cannot be assessed or depth of penetration not specified

T0 - No evidence of primary tumor
Tis - Carcinoma in situ (mucosal); intraepithelial or invasion of the lamina propria
T1 - Tumor invades submucosa
T2 - Tumor invades muscularis propria
T3 - Tumor invades through the muscularis propria into the subserosa or into non-
peritonealized pericolic or perirectal tissue
T4 - Tumor directly invades other organs or structures and/or perforates the visceral
peritoneum

Regional lymph nodes (N) include the following:

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NX - Regional lymph nodes cannot be assessed

N0 - No regional lymph node metastasis
N1 - Metastasis in 1-3 pericolic or perirectal lymph nodes
N2 - Metastasis in 4 or more pericolic or perirectal lymph nodes
N3 - Metastasis in any lymph node along the course of a named vascular trunk

Distant metastasis (M) include the following:

MX - Presence of metastasis cannot be assessed

M0 - No distant metastasis
M1 - Distant metastasis

Table 1. Comparison of AJCC Definition of TNM Staging System to Dukes Classification. (Open
Table in a new window)

Rectal Cancer Stages TNM Staging Duke Staging 5-Year Survival

Stage I T1-2 N0 M0 A >90%

Stage II A T3 N0 M0 B 60%-85%

B T4 N0 M0 60%-85%

Stage III A T1-2 N1 M0 C 55%-60%

B T3-4 N1 M0 35%-42%

C T1-4 N2 M0 25%-27%

Stage IV T1-4 N0-2 M1 5%-7%

The TNM stage – dependent 5-year survival rate for rectal carcinomas is as follows [36] :

Stage I - 90%
Stage II - 60-85%
Stage III - 27-60%
Stage IV - 5-7%

Treatment & Management

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