PEPID Connect Help
View Tutorial
Contact PEPID Support
Suggest an edit
Current tool:
Current monograph:
Hello, PEPID User
PEPID
Hello, PEPID User
| | |
Subsections
Colon Cancer: Overview

Oncology

Colon Cancer: Overview

Background

  1. Most common GI malignancy
  2. is the third most common cancer in men and women in the United States
  3. Approximately 140,000 new cases/year, 60,000 deaths/year; low incidence in underdeveloped countries; risk increases with age
  4. Over time, these abnormal growths enlarge and ultimately degenerate to become adenocarcinomas
  5. In the United States, colorectal cancer (CRC) ranks second to lung cancer as a cause of cancer mortality
  6. A study estimated that in 2020 approximately 147,950 new CRC cases would have been diagnosed and 53,200 individuals would have died of the disease
  7. Between 2011 and 2015, the average annual incidence rates per 100,000 population were 45.9 and 34.6 for men and women respectively
  8. CRC incidence and mortality rates have shown a steady decline of approximately 1.7% and 3.2%, respectively per year.
  9. The decline began in the mid-1980s and has accelerated since the early 2000s.
  10. It is believed to be driven by changes in risk factors, early detection of cancer through CRC screening, and removal of precancerous polyps with colonoscopy, in addition to advances in surgical and treatment approaches.

Pathophysiology

  1. Majority of colorectal cancers arise from adenomatous polyps or clusters of abnormal cells in the glands covering the inner wall of the colon
  2. Proposed mechanisms of oncogenesis 7, 8
    • Chromosomal instability pathway (CIN); most common
      • Somatic BRAF mutation
        • Present in 5-15% of CRCs
        • Associated with increased kinase activity
        • Poor prognostic indicator
      • Somatic KRAS mutation
        • Occurs early in carcinogenesis
        • Confers elevated Ras activity, ERK activity, and EGFR activity
      • Somatic TP53 mutation
        • Inhibits apoptosis
        • Increasingly found in malignant polyps and invasive CRCs
      • Earliest identifiable CIN pathway lesion is the dysplastic aberrant crypt focus which precedes the development of a polyp
    • CpG island methylator phenotype pathway (CIMP); second most common pathway to sporadic CRC
      • Methylation of the CG-rich segments of DNA, inactivating expression of key tumor suppressor genes
      • Sessile serrated adenomas are the main pathological precursor
    • Microsatellite instability pathway (MSI)
      • Microsatellites are nucleotide repeat sequences
      • Instability refers to a discrepancy in the number of nucleotide repeats found within the microsatellite regions in tumor versus germline DNA
      • Mismatch repair dysfunction and/or mutations in associated heterodimers (e.g., MLH1, MLH2) results in MSI
      • MSI pathway is implicated in hereditary nonpolyposis colorectal cancer (HNPCC)
  3. Risk factors include
  4. Location colon cancers changing 2/3 CA in left colon; rectum 22%; sigmoid 35%; descending colon 6%; transverse 13%; ascending 8%; cecum 15%
  5. Risk of malignancy proportional to size of polyp (>1 cm)

Diagnostics

  1. Signs and symptoms: Over 50 years old with Iron deficiency anemia, rectal bleed, or positive fecal occult blood
    • Bowel symptoms with large tumors include a change in bowel habits (frequency, consistency), new-onset constipation, alternating diarrhea & constipation; decreased caliber stools & tenesmus suggest rectal lesions
  2. +/- Abdominal mass, or periumbilical mass (metastasis to umbilical remnant)
    • Virchow's node: Left supraclavicular node from the thoracic duct
    • Rectal exam: mass (intraluminal) narrowed opening (circumferential lesion) metastasis in rectovesical pouch
  3. Diagnostic workup: colonoscopy, CEA, CXR, CT abdomen, and pelvis
    • CEA elevated with carcinoma, but non-specific (not a screening tool)
    • Barium enema: +/- irregular mass creating contour defect, encircling constricting mass ("napkin-ring")
    • Colonoscopy: diagnosis by biopsy; treatment is removal of polyps
    • CT abdomen: oral contrast for GI organs in the abdomen and pelvis; rectal administration of contrast enhances images of the distal gastrointestinal tract (Go to Evidence-Based Inquiry)
  4. Staging is dependent on depth of tumor invasion and extent of disease; TNM staging preferred over Duke's
  5. For TNM staging, see AJCC Colon Cancer Stages
  6. Modified Dukes Staging (View image)
    • Dukes A: tumor limited to mucosa; 5-year survival 95%
    • Dukes B: tumor through submucosa; 5-year 60-80%
      • B1: not extending beyond muscularis propria
      • B2: penetrates muscularis propria to serosa
    • Dukes C: tumor involving local lymph nodes; 5-year survival 20-50%; C1 + LN and not invading muscularis propria; C2 + LN and through muscularis propria to serosa
    • Dukes D: tumor with distant metastasis; 5-year survival <5%
  7. Fong Clinical Risk Score for Colorectal Cancer Recurrence (Open Calc)
  8. Graded Prognostic Assessment for GI Cancer (GI-GPA) (Open Calc)

Therapeutics

  1. Primarily surgery alone or surgery with chemotherapy before or after according to stage (see www.nccn.org for detailed treatment guidelines)
    • Stage I
      • If completely resected with biopsy, no additional surgery required
      • If deep invasion into stalk of polyp, high grade, lymphatic invasion or positive margins = colectomy advised
      • May consider colectomy with broad-based villous or villoglandular adenoma or fragmented specimen
    • Stage II
      • Usually resection alone (as above)
      • Adjuvant chemotherapy (can suggest clinical trial) for perforations, close margins or clinical obstruction
      • Consider adjuvant radiation/chemoradiotherapy with T3 or T4 with close, indeterminate or positive margins
    • Stage III
      • Fluorouracil (5FU) plus leucovorin
      • Varied opinions re: the efficacy of high, intermediate or low dose at different durations
      • Consider post-op radiotherapy with T4N1, perforation or fistula
    • Stage IV
      • May defer surgery for chemotherapy if asymptomatic right-sided lesion
      • May resect isolated ovarian metastases
      • Post-hepatic resection, hepatic artery infusion plus systemic chemotherapy better than systemic alone
      • Chemotherapy at this stage usually 5FU / leucovorin and irinotecan (oxaliplatin)
  2. Chemotherapy & radiation are effective for rectal cancer; may receive neoadjuvant chemo prior to tumor resection
  3. Synchronous colon cancers 10
    • May be treated by two separate resections or subtotal colectomy
  4. Tumor-related emergencies 10
    • Acute hemorrhaging
      • Resuscitation indicated followed by attempts to localize bleeding site
      • Options for preoperative localization include
        • CT angiography (preferred); combine with angiographic embolization
        • Radionuclide imaging
        • Conventional angiography, and
        • Colonoscopy; also offers a therapeutic option
      • When nonsurgical options fail to localize or control bleeding, surgical intervention is indicated
    • Perforated colon cancer
      • Resection of tumor should be performed according to surgical principles
    • Obstruction
      • Left-sided obstructive colon cancer, curable
        • Consider initial colectomy or initial endoscopic stent decompression and interval colectomy
      • Right or transverse obstructive colon cancer, curable
        • Oncologic segmental resection with ileocolic anastomosis in most cases
        • Consider also endoscopic stent decompression and laparoscopic technique for interval colectomy
        • Alternative: emergent colectomy

American College of Radiology (ACR) Appropriateness Criteria for Local Excision of Rectal Cancer

  1. uT1N0 rectal cancers
    • Negative margins
    • No clinical or histological factors associated with risk for local recurrence
    • Excellent local control following local excision (LE) alone
    • Risk factors associated with increased risk for local recurrence include
      • Tumor size >2.5 cm
      • Adverse pathologic features (high-grade tumors and lymphovascular or perineural space invasion)
      • Tumors occupying >40% of the rectum
  2. uT2N0 rectal cancers
    • May be less reliably staged with endorectal ultrasound (EUS), indicating a higher risk for subclinical nodal involvement and risk for recurrence
    • Larger tumor size may increase risk for local recurrence even if margins are uninvolved and no other adverse features are identified on final pathology
    • Addition of pelvic radiation with or without chemotherapy may reduce the risk of local recurrence
    • Neoadjuvant therapy should be considered
  3. uT3N0 rectal cancers
    • Standard of care remains low anterior resection (LAR) or abdominoperineal resection (APR) following neoadjuvant therapy
    • Use of LE should be considered only in setting of clinical trial or for patients with severe comorbidities limiting surgery
  4. Workup
    • All patients should receive
      • Full colonoscopy with biopsy
      • Pathology review
      • Proctoscopy
      • Carcinoembryonic antigen
      • CT of the chest, abdomen, and pelvis
  5. Patient selection
    • Best candidates for LE include small (<4 cm), low-lying tumors confined to the muscularis propria
    • LE is not recommended in
      • Patients with adverse pathologic features (mucinous/signet ring histology, poor differentiation, lymphovascular space invasion)
      • Patients with tumors that occupy more than 40% of the rectum (high risk for local recurrence)
  6. Surgical technique
    • Three operative approaches for LE of a distal rectal lesion
      • Transanal endoscopic microsurgery
        • Most used
        • Allows for complete excision of rectal neoplasm
        • Associated with less morbidity
        • Safe following chemoradiation therapy
      • Posterior trans-sphincteric (York-Mason procedure)
        • Posterior approach with dissection above or below the levator ani to the rectum
      • Posterior proctotomy (Kraske procedure)
        • Same approach as York-Mason procedure

Guidelines on Colorectal Cancer by the American Society of Clinical Oncology

  1. ASCO endorses 2014 European Society for Medical Oncology (ESMO) guidelines for persons at risk for hereditary colorectal cancer syndromes with some specific stipulations
    • All colorectal patients should be assessed for a hereditary cancer syndrome at time of cancer diagnosis
      • Full germline genetic testing for Lynch syndrome should include DNA sequencing and large rearrangement analysis
      • For non-Caucasians, consider full sequencing of MUTYH (founder mutations differ in other ethnic groups)
      • Consider analysis of BRAF V600E mutation, or methylation of MLH1 promoter, when loss of MLH1/PMS2 protein expression is observed
      • Corresponding germline genetic testing should be performed if loss of any other protein is observed (MSH2, MSH6, PMS2)
    • In patients with colorectal cancer, a diagnosis of Lynch syndrome, familial adenomatous polyposis (FAP) or other genetic syndromes can influence clinical management
    • Tumors should be tested for DNA mismatch repair (MMR) deficiency using immunohistochemistry for MMR proteins and/or microsatellite instability (MSI)
      • MMR/MSI testing may be useful to identify a subset of stage II patients who are at a low risk of recurrence and in whom the benefits of chemotherapy are unlikely
  2. ASCO screening guidelines in families with classic FAP
    • Carriers of APC mutations, or those at risk, should undergo sigmoidoscopy once every 2 years beginning at age 10 years, and repeated every 1-2 years
  3. ASCO FAP post-surgical surveillance
    • Post-surgical surveillance interval should be on a case-by-case basis
      • Recommended interval
        • Every 6-12 months if rectal tissue remains
        • Every 6 months to 5 years if an ileoanal pouch is present

ESMO Localized colon cancer 2020 guidelines

  1. Invasive Screening
    • A complete colonoscopy is the recommended method for colorectal cancer (CRC) screening in average-risk men and women
      • The optimal age range for testing is 50-74 years, with an optimal repetition interval for a negative test of 10 years.
    • Flexible sigmoidoscopy (FS) every 5–10 years may be an alternative for patients who refuse colonoscopy.
      • The combination of FS with a yearly FOBT is recommended to reduce the risk of a right colon tumor
    • Other invasive tests, including capsule colonoscopy, are not recommended for screening
  2. Noninvasive Screening
    • Non-colonoscopic tests are recommended in average-risk men and women age ≥50 years who are not already taking part in colonoscopic screening programs.
      • The optimal frequency of testing is every year and no later than every 3 years
      • When the test results are positive, a colonoscopy must be carried out at the earliest convenience
      • Fecal immunochemical testing (FIT) appears to be superior to high-resolution guaiac FOBT with respect to the detection rate and positive predictive value for adenomas and cancer
  3. Diagnosis
    • In the absence of indications for urgent tumor resection, a total colonoscopy is recommended for diagnostic confirmation of colon cancer and to rule out synchronous tumors.
    • If full colonoscopy is not possible, left-sided colonoscopy may be combined with CT colonoscopy.
      • If a complete colonoscopy is not done before or during the surgical procedure, it should be carried out within 3–6 months following tumor resection.
    • The recommended workup also includes the following:
      • Comprehensive physical examination
      • Laboratory studies
        • Complete blood count
        • Coagulation studies
        • Liver function panel
        • Kidney function panel
        • Albumin level,
        • Carcinoembryonic antigen (CEA) assay
      • Thoracic, abdominal, and pelvic CT with contrast
      • Contrast-enhanced MRI if needed, to evaluate the relationship of locally advanced tumors with surrounding structures or to define ambiguous liver lesions
  4. Treatment
    • En bloc endoscopic resection of the polyp is sufficient for noninvasive adenocarcinomas (pTis—i.e., intraepithelial or intramucosal)
    • Invasive carcinoma (pT1) in a polyp requires a thorough review with the pathologist and surgeon.
      • High-risk features mandating surgical resection with lymphadenectomy include
        • Lymphatic or venous invasion,
        • Grade 3 differentiation
        • Significant (grade >1) tumor budding

Follow-Up

  1. Recommended follow-up protocol
    • Periodic history and physical, serial serum tumor markers, annual CT and colonoscopy
    • Assess for signs/symptoms of obstruction
    • Assess for treatment complications, recurrence; provide reassurance
  2. If no evidence of disease or complication
    • Colonoscopy within 1 year of resection; if no polyps, every 3-5 years
    • Office exams every 3 months for 2 years then every 6 months for 3 years
    • Abdominal CT if any abnormality
  3. Assess mental health status in both acute and long-term survivorship; refer for cognitive therapy when indicated

Prevention

  1. Screening
    • USPSTF
      • USPSTF recommends screening for colorectal cancer in adults aged 45 to 49 years (grade B recommendation)
      • USPSTF recommends screening for colorectal cancer in all adults aged 50 to 75 (grade A recommendation)
      • The USPSTF recommends that clinicians selectively offer screening for colorectal cancer in adults aged 76 to 85 years,
        • Based on consideration of the patient's overall health, prior screening history, and preferences (grade C recommendation).
    • Cologuard
      • A non-invasive DNA screening test for colorectal cancer, FDA approved 2014
      • Using a stool sample detects hemoglobin and certain mutations associated with colorectal cancer in the DNA of cells shed by adenomas
      • Patients with positive test results are advised to undergo a diagnostic colonoscopy
  2. American Cancer Society CRC Screening Recommendations (2021)
    • We recommend CRC screening in average-risk individuals between ages 50 and 75 years to reduce incidence of advanced adenoma, CRC, and mortality from CRC.
    • We suggest CRC screening in average-risk individuals between ages 45 and 49 years to reduce incidence of advanced adenoma, CRC, and mortality from CRC.
    • We suggest that a decision to continue screening beyond age 75 years be individualized.
    • We recommend colonoscopy and FIT as the primary screening modalities for CRC screening.
    • We suggest consideration of the following screening tests for individuals unable or unwilling to undergo colonoscopy or FIT: flexible sigmoidoscopy, multitarget stool DNA test, CT colonography or colon capsule.
    • We suggest against Septin 9 for CRC screening.
    • Screening options
      • We recommend that the following intervals should be followed for screening modalities:
        • FIT every 1 year
        • Colonoscopy every 10 years
          Strong recommendation; low-quality evidence
      • We suggest that the following intervals should be followed for screening modalities:
        • Multitarget stool DNA test every 3 years
        • Flexible sigmoidoscopy every 5–10 years
        • CTC every 5 years
        • CC every 5 years
          Conditional recommendation; very low-quality evidence

Evidence-Based Content

  1. Is aspirin effective for primary prevention of colon cancer?
  2. What's the most effective way to screen patients with a family history of colon cancer?
  3. Is cold loop resection as safe and effective as loop cautery for polypectomy?
  4. Does dietary fiber prevent colorectal cancer?
  5. How should we screen patients with a family history of colon cancer?
  6. When is contrast indicated for thoracic and abdominal computed tomography scanning?
  7. Is screening colonoscopy more effective than annual FOBT in improving morbidity and mortality for colon cancer screening in adults?

References

  1. Stoffel EM, Mangu PB, Gruber SB, et al. Hereditary colorectal cancer syndromes: American Society of Clinical Oncology Clinical Practice Guideline endorsement of the familial risk-colorectal cancer: European Society for Medical Oncology Clinical Practice Guidelines. J Clin Oncol. 2015;33(2):209-217.
  2. Balmana J, Balaguer F, Cervantes A, Arnold D, Group EGW. Familial risk-colorectal cancer: ESMO Clinical Practice Guidelines. Ann Oncol. 2013;24 Suppl 6:vi73-80.
  3. Jones WE, 3rd, Thomas CR, Jr., Herman JM, et al. ACR appropriateness criteria (R) resectable rectal cancer. Radiation oncology. 2012; 7:161.
  4. Alberts SR, Sargent DJ, Nair S, et al. Effect of oxaliplatin, fluorouracil, and leucovorin with or without cetuximab on survival among patients with resected stage III colon cancer: a randomized trial. JAMA. 2012;307(13):1383-1393.
  5. Lao IH, Wang YJ, Mak CW, et al. Computed tomography has low sensitivity for the diagnosis of early colon cancer. Colorectal Dis. 2013.
  6. Matuchansky C. Screening flexible sigmoidoscopy for colon cancer. N Engl J Med. 2012;367(11):1065; author reply 1065-1066.
  7. Patel P, Yang VW. Colorectal Neoplasms. In: Srinivasan S, Friedman LS, eds. Sitaraman and Friedman's Essentials of Gastroenterology 2nd ed. Hoboken, NJ: Wiley-Blackwell; 149-163.
  8. Worthley DL, Leggett BA. Colorectal cancer: molecular features and clinical opportunities. Clin Biochem Rev. 2010;31(2):31-38.
  9. Wolf AMD, Fontham ETH, Church TR, et al. Colorectal cancer screening for average-risk adults: 2018 guideline update from the American Cancer Society. CA Cancer J Clin. 2018.
  10. Vogel JD, Eskicioglu C, Weiser MR, Feingold DL, Steele SR. The American Society of Colon and Rectal Surgeons Clinical Practice Guidelines for the Treatment of Colon Cancer. Dis Colon Rectum. 2017;60(10):999-1017.
  11. Localized Colon Cancer Clinical Practice Guidelines (ESMO, 2020). Available at: Localized Colon Cancer Guidelines (ESMO, 2020)
  12. ACG Clinical Guidelines: Colorectal Cancer Screening 2021.Available at: https://journals.lww.com/ajg/Fulltext/2021/03000/ACG_Clinical_Guidelines__Colorectal_Cancer.14.aspx

Contributor(s)

  1. Hernandez, James, DO
  2. Tom, Jubil, MD

Updated/Reviewed: July 2021