Colorectal%20cancer Diagnosis

• Digital rectal examination (DRE) is an important part of the physical examination
• It can detect lesions located up to 7 cm from the anal verge

Fecal Occult Blood Testing

• Guaiac-based testing (gFOBT)
  • Can be performed in the physician’s clinic
  • Blood in the stool is detected via the reaction of pseudoperoxidase with heme or hemoglobin
  • Colonoscopy should be done following a positive gFOBT
  • Should be performed on 3 consecutive stool samples in a patient on a prescribed diet

• Fecal immunohistochemical test (FIT) or immunochemical fecal occult blood test (iFOBT)
  • Is done in clinical laboratories
  • Depends on the reaction with human globin
  • Appears to be superior to gFOBT with respect to detection rate and positive predictive value for adenomas and cancer
  • Less likely to react to upper GI bleeding
  • Advantage: Does not detect hemoglobin from nonhuman dietary sources
  • Like gFOBT, FIT may not detect a tumor which is not bleeding, hence, may require multiple stool testing

Stool DNA (sDNA)

• DNA shed from the stool is tested for molecular changes
• Has been shown to detect significant colorectal cancers and adenomas

Tumor Markers

• Eg carcinoembryonic antigen (CEA), RAS mutation, BRAF mutation, microsatellite instability (MSI) testing
• May be used to predict prognosis, recurrence rates, and outcome marker
• Preoperative CEA levels may be obtained as baseline measurement for assessment of patient’s response to treatment and prediction of prognosis
• RAS testing should be obtained in all patients with metastatic CRC 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 mCRC
• 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

Risk Stratification

• Average Risk
  • Includes individuals ≥45 years with no history of colorectal cancer, adenoma or sessile serrated polyps (SSP), inflammatory bowel disease and negative family history
• Increased Risk
  • Includes individuals with personal history of colorectal cancer, adenomatous/SSP, inflammatory bowel disease, as well as those with positive family history of colorectal cancer or advanced adenomatous polyps
• High Risk
  • Includes individuals with personal or family history of polyposis syndromes
  • Also includes those with family history of hereditary nonpolyposis colorectal cancer (Lynch syndrome)

Revised Tumors, Nodes and Metastasis (TNM) System

• Proposed by the American Joint Committee on Cancer
• TNM staging is based on the depth of tumor invasion on the colorectal lining (T), the number of regional lymph nodes affected (N), and the presence or absence of distant metastasis (M)
• Colon cancer and rectal cancer share the same staging system since TNM categories show very similar survival outcomes for colon and rectal cancer

Staging of Colorectal Cancer

• Pathologic staging is the single most important prognostic factor following surgical resection of tumors

Staging Evaluation

• CT Scan (with contrast) of the chest, abdomen and pelvis is recommended to estimate the stage of colorectal cancer beyond the rectum
  • Chest CT scan is mandatory for assessment of distal metastasis in rectal cancer

• Locoregional extent of colorectal cancer is best evaluated during surgical exploration and by pathologic examination of the specimen
  • A minimum of 12 lymph nodes need to be examined to establish N stage
  • In selected cases, preoperative CT scan will aid in identifying involved neighboring structures
  • In locoregional staging of colonic cancer, MRI has no advantage over CT scan

• Preoperative locoregional staging of rectal cancer is needed to plan surgery and when considering need for preoperative adjuvant chemotherapy
• For patients with rectal cancer, magnetic resonance imaging (MRI) should be offered to evaluate the risk of local recurrence
• Endorectal ultrasound may be done in rectal cancer if MRI is contraindicated or if MRI shows disease amenable to local excision
  • Overall accuracy for detecting lymph node metastases is approximately 80%
  • Not a very accurate method for staging rectal cancer
  • Cannot fully visualize large or bulky rectal tumors or areas beyond the immediate primary tumor (eg vascular invasion, tumor deposits)

• Findings from DRE should not be used in staging of colorectal cancer
• All patients with metastatic colorectal cancer should have tumor tissue genotyped for RAS mutations (KRAS and NRAS) and BRAF mutations
  • Performed only in certified laboratories

• All patients with a V600 BRAF mutation appear to have a poorer prognosis

• KRAS/NRAS/BRAF testing may be done on archived specimens, using either the primary tumor or a metastasis
• Fresh biopsies should not be performed solely for the purpose of KRAS/NRAS genotyping
• Testing for universal mismatch repair (MMR) or MSI is recommended for all newly diagnosed colon and rectal cancer patients
  • Performed only in certified laboratories

Flexible Proctosigmoidoscopy

• Safe and more comfortable compared with rigid proctoscopy
• Able to 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)

• High sensitivity and specificity for detecting colonic cancers, premalignant lesions and other symptomatic colonic diseases
• Allows biopsy and histologic confirmation of any suspected colonic lesion and allows excision of adenomatous polyps
• Incomplete colonoscopy may result from obstructing lesions, poor tolerance of procedure, insufficient bowel preparation and presence
• Patients with incomplete colonoscopy should be offered either one of the following:
  • Repeat colonoscopy or
  • Barium enema (BE) or
  • Computed tomographic (CT) colonography (CTC)

• Potential complications include colonic perforation, effects of sedation which may preclude its use in patients with serious neurological or cardiorespiratory disorders
• Limitations include inability to detect small lesions due to blind corners and areas that are difficult to reach like the cecum (double-contrast BE may be done if colonoscopy fails to reach cecum)

Computed Tomographic Colonography (CTC/Virtual Colonoscopy)

• An alternative to colonoscopy or flexible sigmoidoscopy
  • Probably the best alternative for patients with an incomplete colonoscopy or those unable to undergo colonoscopy

• Makes use of CT images that are reconstructed to visualize the colon
• Adequate bowel preparation and distention of the colon are required for success
• 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 CT colonography, perform colonoscopy with biopsy to confirm the diagnosis, unless it is contraindicated

Double-contrast Barium Enema

• No longer recommended as a screening option
• Less sensitive compared to colonoscopy

Endoscopic Ultrasound

• Studies have shown its high sensitivity (94%) for assessing the depth of tumor penetration and high specificity (86%) in evaluating local tumor invasion
• Alternative tool if pelvic MRI is contraindicated

Magnetic Resonance Imaging (MRI)

• Has a high sensitivity for assessing tumor depth but is less specific compared with endoscopic ultrasound
• Has the potential to provide useful information in the prediction of circumferential resection margin prior to radical surgery in patients with rectal CA
• Has the advantage of being able to provide images of the soft tissue structures in the mesorectum