Screening and Diagnosis
Fecal occult blood testing
Fecal occult blood testing (FOBT) consists of guaiac-based testing (gFOBT), which can be performed in the doctor's office, or a fecal immunohistochemical test (FIT), which is usually processed in clinical laboratories. The difference between these tests is based on the detected analyte. Blood in the stool detected by gFOBT depends on the reaction of a pseudoperoxidase with heme or hemoglobin, whereas FIT depends on the reaction with globin. For these tests, two samples should be collected from three consecutive bowel movements. The majority of the adenomas and CRCs go undetected because they usually are not bleeding at the time of the test. Newer gFOBT and FIT appear to have a better sensitivity than older tests without sacrificing specificity.
Three large, prospective, randomized, controlled clinical trials have demonstrated a 15% to 33% decrease in CRC mortality over an 8- to 13-year period of follow-up in those individuals randomized to undergo FOBT. A positive FOBT result should be followed by colonoscopy.
Stool DNA testing
Stool DNA (sDNA) testing takes advantage of molecular changes or mutations that occur in the carcinogenesis of CRC. DNA shed in the stool is analyzed for molecular changes. Multiple targets, including mutations in KRAS, p53, APC, and BAT 26 (which can be a surrogate marker for MSI), are analyzed. There are no data on the performance of sDNA for screening; however, the test has been shown to be able to detect both significant adenomas and CRCs.
Digital rectal examination
Digital rectal examination should be an integral part of the physical examination. It can detect lesions up to 7 cm from the anal verge.
Sigmoidoscopy
Flexible proctosigmoidoscopy is safe and more comfortable than examination using a rigid proctoscope. Almost 50% of all colorectal neoplasms are within the reach of a 60-cm sigmoidoscope. Even though flexible sigmoidoscopy visualizes only the distal portion of the colorectum, the identification of adenomas can lead to colonoscopy. When we add the percentage of colorectal neoplasms in the distal 60 cm of the colorectum to the percentage of patients with distal polyps leading to complete colonoscopy, 80% of those individuals with a significant neoplasm anywhere in the colorectum can be identified. Four prospective, randomized, controlled trials evaluating flexible sigmoidoscopy for screening have been conducted in the United States and Europe, but not all the results are yet available. In the United Kingdom, in a prospective randomized study of more than 100,000 individuals aged 55 to 64 years, a single flexible sigmoidoscopy reduced CRC incidence by 33% and mortality by 43%. Similar results were reported in the Italian randomized study in which in the per-protocol analysis, CRC incidence was reduced by 31% and CRC-related mortality was reduced by 38% in those individuals aged 55 to 64 years who underwent single flexible sigmoidoscopy compared with controls. Based on the area examined by the sigmoidoscopy, the incidence of distal CRC (rectum and sigmoid colon) was reduced by 50% (hazard ratio [HR] = 0.50; 95% CI, 0.42–0.59; secondary outcome).
Colonoscopy
This color atlas includes images of adenomatous and nonadenomatous polyps, adenocarcinomas, surgical anastomosis, diverticula, lipoma, and scattered and clustered pseudopolyps
Optical. This form of colonoscopy provides information on the mucosa of the entire colon, and its sensitivity in detecting tumors is extremely high. Most physicians consider colonoscopy to be the best screening modality for CRC. Colonoscopy can be used to obtain biopsy specimens of adenomas and carcinomas and permits the excision of adenomatous polyps. For this reason, colonoscopy is the only screening modality ever shown to reduce the incidence of cancer in screened individuals. Colonoscopy is the best follow-up strategy for evaluating patients with a positive gFOBT and the best screening modality for high-risk patients.
Limitations of colonoscopy include its inability to detect some polyps and small lesions because of blind corners and mucosal folds and the fact that sometimes the cecum cannot be reached. A supplementary double-contrast barium enema may be needed if a colonoscopic examination fails to reach the cecum.
CT virtual. This form of colonoscopy utilizes CT images that are reconstructed to visualize the colon. It requires a bowel preparation and adequate distention of the colon for success. There is no prospective randomized study demonstrating that colonoscopic CT reduces CRC mortality. However, a trial comparing optical colonoscopy with colonoscopic CT resulted in similar detection rates for advanced neoplasia.
Barium enemas
Barium enemas can accurately detect CRC; however, the false-negative rate associated with double-contrast barium enemas ranges from 2% to 61% because of misinterpretation, poor preparation, and difficulties in detecting smaller lesions. A supplementary colonoscopy may be needed if a double-contrast barium enema does not adequately visualize the entire colon or to obtain histopathology or perform polypectomy in the event of abnormal findings. There is no role for single-contrast barium enema. If this modality is to be used, a well-conducted double-contrast barium enema needs to be performed.
American Cancer Society guidelines on screening and surveillance for the early detection of colorectal adenomas and cancer—Average risk
A joint guideline from the American Cancer Society, the US Multi-Society Task Force on CRC, and the American College of Radiology for screening and surveillance in high-risk individualsRecommendations for average-risk individuals
Adults at average risk should begin CRC screening at age 50. The ACS guidelines on screening and surveillance for the early detection of colorectal adenomatous polyps and cancer provide several options for screening average-risk individuals (Table 4).
Recommendations for screening and surveillance of high-risk individuals are given in Table 5.
Treatment of endoscopically removed polyps
Adenomatous colon polyps should be completely removed endoscopically to prevent progression to malignancy. Colon polyps with severe dysplasia or carcinoma in situ can also be managed with colonoscopic polypectomy as long as the entire polyp is removed. A malignant polyp is defined as one with cancer invading through the muscularis mucosa and into the submucosa (pT1).
Management of malignant polyps removed by colonoscopy is somewhat controversial. In general, malignant polyps can be removed colonoscopically as long as they can be removed with a confirmed negative margin and do not invade the submucosa beneath the polyp stalk, do not have lymphovascular invasion, or are poorly differentiated. These characteristics increase the risk of nodal metastases.
Studies from Japan and the United States have correlated the incidence of lymph node metastases with the level of submucosal involvement. Individuals with cancer in polyps invading the upper third of the submucosa have a low risk of nodal metastases, whereas those invading the lower third have up to a 25% incidence of nodal metastases. Sessile polyps with submucosal invasion should probably be removed by colon resection. Each situation should be individualized according to the histology, prognostic factors, extent of submucosal invasion, and completeness of excision. The comorbidities and general health of the patient are also factors to consider.
Initial workup
An initial diagnostic workup for patients with suspected colorectal tumors should include a complete history, including a three-generation family history, and a physical examination. It should also include:
• Digital rectal examination and FOBT
• Colonoscopy
• Biopsy of any detected lesions
Adequate staging prior to surgical intervention requires:
• CT scan of the chest, abdomen, and pelvis
• Endorectal ultrasonography or MRI to evaluate and appropriately stage a rectal cancer for potential neoadjuvant therapy
• Complete blood cell count with platelet count
• Liver and renal function tests
• Urinalysis
• Measurement of carcinoembryonic antigen (CEA) level; if CEA levels are elevated preoperatively, postoperative CEA levels should be monitored every 3 months for 3 years in patients with stage II or III CRC and every 6 to 12 months thereafter
• Endoscopic ultrasonography or MRI of the pelvis for rectal cancers
In monitoring response to therapy for metastatic cancer, CEA levels should be measured every 1 to 8 months during active treatment.
FDG-PET scanning
18F-fluorodeoxyglucose (FDG)-positron emission tomographic (PET) scanning has emerged as a highly sensitive study for the evaluation of patients who have metastatic disease. Although not usually recommended in the evaluation of early-stage primary disease, this modality can aid in the staging of recurrence.
Pathology
Adenocarcinomas
Adenocarcinomas constitute 90% to 95% of all large-bowel neoplasms. These tumors consist of cuboidal or columnar epithelia with multiple degrees of differentiation and variable amounts of mucin.
Mucinous adenocarcinoma
Mucinous adenocarcinoma is a histologic variant characterized by huge amounts of extracellular mucus in the tumor and the tendency to spread within the peritoneum. Approximately 10% of colorectal adenocarcinomas are mucinous. It is more commonly seen in younger patients.
Signet-ring cell carcinoma
Signet-ring cell carcinoma is an uncommon variant, accounting for 1% of colorectal adenocarcinomas. These tumors contain large quantities of intracellular mucinous elements (causing the cytoplasm to displace the nucleus) and tend to involve the submucosa, making their detection difficult with conventional imaging techniques.
Other tumor types
Squamous cell carcinomas, small-cell carcinomas, carcinoid tumors, and adenosquamous and undifferentiated carcinomas also have been found in the colon and rectum. Nonepithelial tumors, such as sarcomas and lymphomas, are exceedingly rare.
Metastatic spread
CRC has a tendency toward local invasion by circumferential growth and for lymphatic, hematogenous, transperitoneal, and perineural spread. Longitudinal spread is usually not extensive, with microscopic spread averaging only 1 to 2 cm from gross disease, but radial spread is common and depends on anatomic location.
The most common site of extralymphatic involvement is the liver, with the lungs the most frequently affected extra-abdominal organ (more common site than liver in rectal cancer). Other sites of hematogenous spread include the bones, kidneys, adrenal glands, and brain, although metastases can spread to any organ.
Staging and Prognosis
The TNM staging classification, which is based on the depth of tumor invasion in the intestinal wall, the number of regional lymph nodes involved, and the presence or absence of distant metastases, has largely replaced the older Dukes' classification scheme (Table 6).
AJCC staging for cancer of the colon and rectumPathologic stage
Pathologic stage is the single most important prognostic factor following surgical resection of colorectal tumors. The prognosis for early stages (I and II) is favorable overall, in contrast to the prognosis for advanced stages (III and IV). However, there appears to be superior survival for patients with stage III disease whose disease is confined to the bowel wall (ie, ≤ T2, N+).
Histologic grade
Histologic grade may be correlated with survival. Five-year survival rates of 56% to 100%, 33% to 80%, and 11% to 58% have been reported for grades 1, 2, and 3 colorectal tumors, respectively.
Other prognostic factors
Other prognostic factors (such as age at diagnosis, presurgical CEA level, sex, presence and duration of symptoms, site of disease, histologic features, obstruction or perforation, perineural invasion, venous or lymphatic invasion, ploidy status, and S-phase fraction) have not consistently been correlated with overall disease recurrence and survival. Furthermore, the size of the primary lesion has had no influence on survival. Elevated expression of thymidylate synthase (TS) and allelic loss of chromosome 18 have been correlated with a poor prognosis. MSI or deficient mismatch repair status has been correlated as an independent prognostic factor for survival, favoring patients with unstable tumors (MSI-H).
