colorectal%20cancer
COLORECTAL CANCER
Colorectal cancer is a carcinoma arising from the luminal surface of the colon.
It is the 2nd most common cancer in women and third most common cancer in male worldwide. It commonly arises from adenomatous polyps.
It is strongly linked to age with 83% occurring in people ≥60 years old.
Rectal cancer is defined as cancerous lesions located within 12 cm of the anal verge.

Physical Examination

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

Laboratory Tests

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
  • Fecal immunohistochemical test (FIT) or immunochemical fecal occult blood test (iFOBT)
    • Is done in clinical laboratories
    • Depends on the reaction with globin
    • Appears to be superior to gFOBT with respect to detection rate & positive predictive value for adenomas & cancer
    • Less likely to react to upper GI bleeding
    • 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 & adenomas
  • Does not require any preparation but is more expensive than other stool tests
  • As with other stool tests, a colonoscopy is required to investigate further should results become positive

Flexible Proctosigmoidoscopy

  • Safe & 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 & specificity for detecting colonic cancers, premalignant lesions & other symptomatic colonic diseases
  • Allows biopsy & histologic confirmation of any suspected colonic lesion & allows excision of adenomatous polyps
  • Incomplete colonoscopy may result from obstructing lesions, poor tolerance of procedure, insufficient bowel preparation & presence
  • Patients with incomplete colonoscopy should be offered either one of the following:
    • Repeat colonoscopy or
    • Barium enema or
    • Computed tomographic (CT) colonography
  • 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 & areas that are difficult to reach like the cecum (double-contrast BE may be done if colonoscopy fails to reach cecum)

Tumor Markers

  • Eg RAS mutation, BRAF mutation, microsatellite instability (MSI) testing
  • May be used to predict prognosis, recurrence rates, & outcome marker
  • RAS testing should be obtained in all patients with metastatic CRC & prior to treatment with Cetuximab or Panitumumab
  • MSI & 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 & toxicity include dihydropyrimidine dehydrogenase (DPD) test & 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

Assessment

Risk Stratification

Average Risk

  • Includes individuals ≥50 years with no history of colorectal cancer, adenoma, inflammatory bowel disease & negative family history

Increased Risk

  • Includes individuals with personal history of colorectal cancer, adenomatous/sessile serrated polyps, 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)

Staging

Revised Tumors, Nodes & 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), & the presence or absence of distant metastasis (M)
  • Colon cancer & rectal cancer share the same staging system since TNM categories show very similar survival outcomes for colon & rectal cancer
Assessment of Primary Tumor (T)
TX Primary tumor cannot be evaluated
T0 No evidence of primary tumor
Tis Carcinoma in situ (intraepithelial penetration of lamina propia)
T1 Tumor reaches submucosa
T2 Tumor penetrates muscularis propia
T3 Tumor reaches muscularis propia into the pericolorectal tissues
T4a Tumor reaches the surface of the peritoneal viscera
T4b Tumor adheres to other organs or structures

Assessment of Regional Lymph Nodes (N)
NX Regional lymph nodes cannot be evaluated
N0 No regional nodal metastasis
N1 Metastasis involves 1-3 regional lymph nodes
N1a Metastasis involves 1 regional lymph node
N1b Metastases involves 2-3 regional lymph nodes
N1c No regional lymph node metastasis but with tumor spread in the subserosa, mesentery, or nonperitonealized pericolic or perirectal tissues
N2 ≥4 regional lymph node metastases
N2a Metastases in 4-6 regional lymph nodes
N2b Metastases in ≥7 regional lymph nodes

Assessment for Distant Metastasis (M)
M0 No distant metastasis
M1 Presence of distant metastasis
M1a Metastasis in one organ or site (eg lung, liver, ovary, nonregional node)
M1b Metastases in more than one organ or site or to the peritoneum

Staging of Colorectal Cancer

  • Pathologic staging is the single most important prognostic factor following surgical resection of tumors
Stage 0 Tis N0 M0
Stage I T1-T2 N0 M0
Stage IIA T3 N0 M0
Stage IIB T4a N0 M0
Stage IIC T4b N0 M0
Stage IIIA T1-T2 N1/N1c M0
T1 N2a M0
Stage IIIB T3-T4a N1/N1c M0
T2-T3 N2a M0
T1-T2 N2b M0
Stage IIIC T4a N2a M0
T3-T4a N2b M0
T4b N1-N2 M0
Stage IVA Any T Any N M1a
Stage IVB Any T Any N M1b
  • Staging Evaluation
  • CT Scan (with contrast) of the chest, abdomen & pelvis is recommended to estimate the stage of colorectal cancer
    • No further routine imaging is needed for colon cancer patients
  • Locoregional extent of colorectal cancer is best evaluated during surgical exploration & 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 & 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 approx 80%
    • While it is the most accurate method to preoperatively stage rectal cancer, endorectal ultrasound is not indicated for all rectal cancer
    • Largely useful for: (1) early rectal cancer (T1) that is being considered for local surgery (either by transanal endoscopic microsurgery or by transanal local excision; & (2) advanced (T3-4) rectal cancer where neoadjuvant therapy is being considered
  • 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 & NRAS)
    • Performed only in certified laboratories
  • All patients with a V600 BRAF mutation appear to have a poorer prognosis
    • Testing for BRAF mutation is done in qualified/certified laboratories
  • KRAS/NRAS 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

Imaging

Computed Tomographic Colonography (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 & distention of the colon are required for success
  • Inaccurate for lesions measuring <1 cm in size
    • Studies showed high average sensitivity & 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

  • Does not require patient sedation
  • Has the capacity to accurately detect colorectal cancer but false-negative results (ranging from 2-61%) with double-contrast BE may result from poor preparation, misinterpretation, difficulties in detecting smaller lesions
  • Does not provide adequate visualization of rectum & rectosigmoid colon (sigmoidoscopy or colonoscopy are recommended for these regions)
  • Single-contrast barium enema has no role in colorectal cancer diagnosis

Endoscopic Ultrasound

  • Studies have shown its high sensitivity (94%) for assessing the depth of tumor penetration & high specificity (86%) in evaluating local tumor invasion

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
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