eMedicine Specialties > Oncology > Carcinomas of the Gastrointestinal Tract

Rectal Cancer: Differential Diagnoses & Workup

Author: Burt Cagir, MD, FACS, Assistant Professor of Surgery, State University of New York, Upstate Medical Center; Consulting Staff, Director of Surgical Research, Robert Packer Hospital; Associate Program Director, Department of Surgery, Guthrie Clinic
Coauthor(s): Douglas R Trostle, MD, MBA, FACS,, Chairman of Surgery, The Guthrie Clinic and Robert Packer Hospital; Clinical Professor of Surgery, The Medical College of Pennsylvania
Contributor Information and Disclosures

Updated: Sep 25, 2009

Workup

Laboratory Studies

Routine laboratory studies should include a complete blood count; 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 ...

Diagnostics. Staging and workup of rectal cancer patients.

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Diagnostics. Staging and workup of rectal cancer ...

Diagnostics. Staging and workup of rectal cancer patients.


Other Tests

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.
 
Average-risk screening (see Table 1, below): 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 75.14

  • Guaiac-based Fecal Occult Blood Test (gFOBT) 

Perform FOBT yearly by testing 2 samples from each of 3 consecutive stools. If any of the 6 samples 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)

Stool DNA screening is done using polymerase chain reaction of sloughed mucosal cells in stool. This test evaluates for genetic alterations leading 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 gastrointestinal 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 gastrointestinal tract.

  • 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 highly reproducible method of determining the level of rectal cancer and it is not dependent 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, since 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.15

  • 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.15  

  • Combined gFOBT and Flexible Sigmoidoscopy

Theoretically, the combination of these 2 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 (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, and that its use as a screening test for colorectal cancer is declining.14

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. Since 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.

Table 1: Average Risk Colon and Rectal Cancer Patients Who Should be Screened

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Table
Risk Category
Signs and Symptoms
Average risk
No symptoms and age between 50 and 75 years
Average risk
No symptoms requesting screening
Average risk
Change in bowel habits
Rectal and anal bleeding
Unclear abdominal pain
Unclear iron-deficiency anemia
Risk Category
Signs and Symptoms
Average risk
No symptoms and age between 50 and 75 years
Average risk
No symptoms requesting screening
Average risk
Change in bowel habits
Rectal and anal bleeding
Unclear abdominal pain
Unclear iron-deficiency anemia
 

The US Multi-Society Task Force on Colorectal Cancer (USMSTF) has endorsed a variety of cost-effective screening regimens (http://cme.medscape.com/viewarticle/571201).
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 (http://cme.medscape.com/viewarticle/571201).  Testing options that primarily detect cancer in asymptomatic adults 50 years and older include annual gFOBT 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. (http://cme.medscape.com/viewarticle/571201)
 
In summary; 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. 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. (http://cme.medscape.com/viewarticle/571201)

In the United States, colon and rectal cancer screening rates have been averaging between 50% and 60%. In a recent study, 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 Caucasians. Also, overall lower screening rates were identified in patients younger than 65 years of age. Although ethnicity-, gender-, and age-related disparities were observed, screening rates were improved in this equal-access health care system when compared with national averages.16
  • Screening of high-risk patients (see Table 2, below)

People at increased risk for colorectal cancer include those with affected first-degree relatives, those with a family history of FAP or HNPCC, and those with a personal history of adenomatous polyps, colorectal cancer, or IBD.

    • 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 (see Table 2): 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 (see Table 2): 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 localized disease. Random biopsies are performed at specific intervals throughout the colon and rectum. Colectomy is recommended when dysplasia is present.

Table 2: High-Risk Colon and Rectal Cancer Patients Who Should be Included in Surveillance Programs

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Table
Risk Category
Signs and Symptoms
High-risk patients due to family history
Family history of colon and rectal cancer
First-degree relative with adenoma aged younger than 60 years
Genetic family syndromes
HNPCC
FAP
High-risk patients due to personal history
Personal history of inflammatory bowel disease
Personal history of adenomas
Personal history of colon and rectal cancer
Personal history of genetic family syndromes
Risk Category
Signs and Symptoms
High-risk patients due to family history
Family history of colon and rectal cancer
First-degree relative with adenoma aged younger than 60 years
Genetic family syndromes
HNPCC
FAP
High-risk patients due to personal history
Personal history of inflammatory bowel disease
Personal history of adenomas
Personal history of colon and rectal cancer
Personal history of genetic family syndromes

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.17

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 3 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 (see Table 3).

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)

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)

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)

MX - Presence of metastasis cannot be assessed

M0 - No distant metastasis

M1 - Distant metastasis

Table 3: Comparison of AJCC Definition of TNM Staging System to Dukes Classification. Five year stage specific survival is also summarized.
 

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Table
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%
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 follows17 :

Stage I: 90%

Stage II: 60% to 85%

Stage III: 27% to 60%

Stage IV: 5% to 7%

More on Rectal Cancer

Overview: Rectal Cancer
Differential Diagnoses & Workup: Rectal Cancer
Treatment & Medication: Rectal Cancer
Follow-up: Rectal Cancer
Multimedia: Rectal Cancer
References
Further Reading
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Keywords

rectal carcinoma, rectal adenocarcinoma, rectal polyp, rectal cancer, squamous cell carcinoma, anal carcinoma, squamous cell carcinoma of the rectum, colorectal cancer

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Contributor Information and Disclosures

Author

Burt Cagir, MD, FACS, Assistant Professor of Surgery, State University of New York, Upstate Medical Center; Consulting Staff, Director of Surgical Research, Robert Packer Hospital; Associate Program Director, Department of Surgery, Guthrie Clinic
Burt Cagir, MD, FACS is a member of the following medical societies: American College of Surgeons, American Medical Association, and Society for Surgery of the Alimentary Tract
Disclosure: Nothing to disclose.

Coauthor(s)

Douglas R Trostle, MD, MBA, FACS,, Chairman of Surgery, The Guthrie Clinic and Robert Packer Hospital; Clinical Professor of Surgery, The Medical College of Pennsylvania
Douglas R Trostle, MD, MBA, FACS, is a member of the following medical societies: Alpha Omega Alpha, American Association of Clinical Endocrinologists, American Association of Endocrine Surgeons, American College of Physician Executives, American College of Surgeons, American College of Surgeons Oncology Group, American Society of General Surgeons, Pennsylvania Medical Society, Society for Surgery of the Alimentary Tract, Society of Critical Care Medicine, Society of Laparoendoscopic Surgeons, and Wilderness Medical Society
Disclosure: Nothing to disclose.

Medical Editor

Philip Schulman, MD, Chief, Medical Oncology, Department of Medicine, Memorial Sloan-Kettering Cancer Center; Clinical Professor, Department of Medicine, New York University School of Medicine
Philip Schulman, MD is a member of the following medical societies: American Association for Cancer Research, American College of Physicians, American Society of Hematology, and Medical Society of the State of New York
Disclosure: celgene Honoraria Speaking and teaching; Amgen Honoraria Speaking and teaching; genetech/idec Honoraria Speaking and teaching

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Wendy Hu, MD, Consulting Staff, Department of Hematology/Oncology and Bone Marrow Transplantation, Huntington Memorial Medical Center
Wendy Hu, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians, American Society for Blood and Marrow Transplantation, American Society of Hematology, and Physicians for Social Responsibility
Disclosure: Nothing to disclose.

CME Editor

Rajalaxmi McKenna, MD, FACP, Southwest Medical Consultants, SC, Department of Medicine, Good Samaritan Hospital, Advocate Health Systems
Rajalaxmi McKenna, MD, FACP is a member of the following medical societies: American Society of Clinical Oncology, American Society of Hematology, and International Society on Thrombosis and Haemostasis
Disclosure: Nothing to disclose.

Chief Editor

Jules E Harris, MD, Clinical Professor of Medicine, Division of Hematology/Medical Oncology, Department of Internal Medicine, University of Arizona College of Medicine at Tucson; Consulting Staff, Arizona Cancer Center
Jules E Harris, MD is a member of the following medical societies: American Association for Cancer Research, American Association for the Advancement of Science, American Association of Immunologists, American Society of Hematology, and Central Society for Clinical Research
Disclosure: GlobeImmune Salary Consulting; Amplimed Consulting fee Consulting; FibroGen Consulting fee Consulting

 
 
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