Colorectal Cancer Diagnostics

Laboratory Tests and Ancillaries

Fecal Occult Blood Testing  

Guaiac-based testing (gFOBT)  

Guaiac-based testing can be performed in the physician’s clinic. Blood in the stool is detected via the reaction of pseudoperoxidase with heme or hemoglobin. A colonoscopy should be done following a positive gFOBT. It should be performed on three consecutive stool samples in a patient on a prescribed diet.  

Fecal immunohistochemical test (FIT) or immunochemical fecal occult blood test (iFOBT)  

A fecal immunohistochemical test or immunochemical fecal occult blood test is done in clinical laboratories. The principle behind this test depends on the reaction with human globin. It also appears to be superior to gFOBT with respect to detection rate and positive predictive value for adenomas and cancer. Its advantage is that it does not detect hemoglobin from nonhuman dietary sources. It is less likely to react to upper gastrointestinal bleeding and like gFOBT, FIT may not detect a tumor that is not bleeding, hence, may require multiple stool testing.  

Stool DNA (sDNA)  

DNA shed from the stool is tested for molecular changes. It has been shown to detect significant colorectal cancers and adenomas.  

Flexible Proctosigmoidoscopy  

Flexible proctosigmoidoscopy is safe and more comfortable compared with rigid proctoscopy. It can visualize only the distal portion of the colorectum but almost 50% of colorectal cancers are within the reach of a 60-cm sigmoidoscope.  

Colonoscopy (Optical Colonoscopy)  

Colonoscopy has a high sensitivity and specificity for detecting colonic cancers, premalignant lesions, and other symptomatic colonic diseases. It allows biopsy and histologic confirmation of any suspected colonic lesion and allows excision of adenomatous polyps.  

An incomplete colonoscopy may result from obstructing lesions, poor tolerance of the procedure, and insufficient bowel preparation. Patients with incomplete colonoscopy should be offered either a repeat colonoscopy or barium enema (BE) or computed tomographic (CT) colonography (CTC).  

The potential complications of colonoscopy include colonic perforation and the effects of sedation which may preclude its use in patients with serious neurological or cardiorespiratory disorders. Its limitations include the inability to detect small lesions due to blind corners and areas that are difficult to reach like the cecum (double-contrast barium enema may be done if colonoscopy fails to reach the cecum).  

Tumor Markers  

Examples of tumor markers include carcinoembryonic antigen (CEA), KRAS mutation, NRAS exon 2, 3, and 4 mutation, NTRK fusion, BRAF mutation, and mismatch repair (MMR)/MSI testing. They may be used to predict prognosis, recurrence rates, and outcome markers.  

Preoperative CEA levels may be obtained as a baseline measurement for assessment of the patient’s response to treatment and prediction of prognosis. RAS testing should be obtained in all patients with metastatic colorectal cancers (mCRC) and prior to treatment with Cetuximab or Panitumumab.  

MSI and BRAF testing should be conducted together with RAS test for the prognostic measurement of patients with metastatic colorectal cancer.  Universal MSI or mismatch repair (MMR) testing is recommended in all newly diagnosed patients with colon cancer. HER2 amplification by immunohistochemistry or fluorescence in situ hybridization (FISH) is recommended in RAS wild-type patients prior to treatment initiation.  

Biomarkers that may be used for chemotherapy sensitivity and toxicity include dihydropyrimidine dehydrogenase (DPD) test and uridine diphosphate glucuronosyltransferase I family polypeptide A1 (UGT1A1) phenotyping. Excision repair cross-complementation (ERCC1) protein expression test is an option for patients enrolled in clinical trials.  

Imaging

Computed Tomographic Colonography (CTC) or Virtual Colonoscopy  

Computed tomographic colonography is an alternative to colonoscopy or flexible sigmoidoscopy. It is probably the best alternative for patients with incomplete colonoscopy or those unable to undergo colonoscopy. It makes use of CT images that are reconstructed to visualize the colon. Adequate bowel preparation and distention of the colon are required for success. It is inaccurate for lesions measuring <1 cm in size. Studies showed high average sensitivity and specificity for neoplasia ≥10 mm.  

Should a suspicious lesion be detected on computed tomographic colonography, perform colonoscopy with biopsy to confirm the diagnosis, unless it is contraindicated.  

Endoscopic Ultrasound  

Studies have shown that endoscopic ultrasound has high sensitivity (94%) for assessing the depth of tumor penetration and high specificity (86%) for evaluating local tumor invasion. It is an alternative tool if pelvic magnetic resonance imaging (MRI) is contraindicated.  

Magnetic Resonance Imaging (MRI)  

MRI has a high sensitivity for assessing tumor depth and has the potential to provide useful information in the prediction of circumferential resection margin prior to radical surgery in patients with rectal cancer. It has the advantage of being able to provide images of the soft tissue structures in the mesorectum.  

Double-contrast Barium Enema  

Double-contrast barium enema is no longer recommended as a screening option. It is less sensitive compared to a colonoscopy.  

Fluorodeoxyglucose (FDG)-Positron Emission Tomography (PET)  

Fluorodeoxyglucose may be used in patients with increased tumor markers without evidence of metastatic disease, or to identify the extent of metastatic disease prior to surgery.