Large Intestine: Colon Cancer

Colon Cancer

General

  • Third Most Common Cancer Diagnosis
  • Third Most Common Cancer Death
  • Lifetime Risk:
    • Males: 1/22 (4.49%)
    • Females: 1/24 (4.15%)
  • Most Common Site: Sigmoid Colon

Risk Factors

  • Obesity & Physical Inactivity
  • Diet High in Red Meat, Processed Meat & Fat
  • Tobacco & Alcohol
  • Clostridium septicum
  • Inflammatory Bowel Disease
  • Genes: APC, DCC, p53, K-Ras
    • APC is Present in 80% of Sporadic Colon Cancers (No Increased Risk of FAP)
  • *Aspirin May Provide Protection from Development of Colorectal Cancer by Inflammatory Pathway (COX/LOX) Inhibition

Associated Genetic Syndromes

  • *See Oncology: Colorectal Cancer & Polyposis Syndromes
  • Familial Adenomatous Polyposis (FAP)
    • Includes:
      • Gardner’s Syndrome
      • Turcot’s Syndrome
  • Lynch Syndrome (Hereditary Nonpolyposis Colon Cancer/HNPCC)
  • Familial Juvenile Polyposis
  • Mut Y Homolog-Associated Polyposis (MAP)
  • Peutz-Jeghers Syndrome
  • PTEN Hamartoma Tumor Syndrome
    • Includes:
      • Cowden Syndrome
      • Bannayan-Riley-Ruvalcaba Syndrome
      • Cronkhite-Canada Syndrome
  • Serrated Polyposis Syndrome

Sigmoid Adenocarcinoma 1

FAP 2

Appendix-Specific Considerations

  • Adenocarcinoma
    • Most Common Presentation: Acute Appendicitis
    • Mucinous Adenocarcinoma – Most Common Source of Pseudomyxoma Peritonei
  • Carcinoid Tumor

Prognosis

  • Most Important Staging Factor: Nodes
  • Lymphocytic Reaction/Penetration – Improves Prognosis
  • Improved Prognosis:
    • High Microsatellite Instability (MSI-H)
    • Deficient DNA Mismatch Repair (dMMR)
    • Lymphocytic Reaction/Penetration
  • Poor Prognostic Factors:
    • Microsatellite Stable (MSS)
    • Proficient DNA Mismatch Repair (pMMR)
    • Lymphovascular Invasion
    • Mutations – KRAS, NRAS or BRAF
  • 5-Year Survival (By AJCC 7):
    • Stage I: 74.1%
    • Stage II:
      • A: 64.5%
      • B: 51.6%
      • C: 32.3%
    • Stage III:
      • A: 74.0% (Higher Than Stage II)
      • B: 45.0%
      • C: 33.4%
    • Stage IV: 6%
      • Resectable Liver Mets: 35% (Higher)
      • Resectable Lung Mets: 25%

Recurrence/Mets

  • Best Test for Intrahepatic Lesions: Intraoperative US (3-5 mm Resolution)
  • Rates of Distant Colorectal Lesions:
    • Synchronous Benign Polyps: 12-62%
    • Synchronous Cancers: 2-8%
    • Metachronous Cancer: 25-30%
  • Recurrence:
    • 20% Have Recurrence (Most Within First Year)
    • 5% Get A New Primary
    • Rectal CA Higher Risk of Recurrence Than Colon CA
  • Mets:
    • Most Common Site: Liver (Portal Vein)
    • Second Most Common Site: Lung (Iliac Vein)
    • Spinal Mets are from the Rectum (Batson’s Plexus) – Not Colon

Presentation

  • Mostly Asymptomatic When in Early Stages – Diagnosed Through Routine Screening
  • Symptoms:
    • GI Bleeding – Most Common Initial Symptom
    • Iron Deficiency Anemia
    • Constipation or Obstruction – More Common on the Left-Side
    • Abdominal Pain

Preoperative Evaluation

  • Total Colonoscopy
    • To Evaluate for Synchronous Lesions
    • Endoscopic Tattoo to Ease Surgical Resection
  • CT Chest/Abdomen/Pelvis
    • Evaluate Mets
  • Labs (CBC/CMP)
  • Carcinoembryonic Antigen (CEA)
    • Used to Monitor for Recurrent Mets
      • CEA Itself is Not Diagnostic of Colon Cancer
    • Poor Sensitivity for Local Recurrence
    • Should Check for a Baseline Level Preoperatively & Follow Postoperatively
    • CEA is Produced by Normal Tissues in Development but Stops Before Birth

TNM Staging

  • TNM
  T N M
1 Submucosa 1a – 1
1b – 2-3
1c – Discrete Tumor Nodules in Lymph Drainage Area without Identifiable Lymph Node Tissue		 1a – One Distant Organ
1b – ≥ 2 Distant Organs
1c – Peritoneal Mets
2 Into Muscularis Propria 2a – 4-6 LN
2b – ≥ 7 LN
3 Into Serosa
4 4a – Through Serosa
4b – Into Adjacent Tissue/Organs
  • Staging
  T N M
I   T1-2 N0 M0
II A T3 N0 M0
B T4a N0 M0
C T4b N0 M0
III A T1 N1-2a M0
  T2 N1 M0
B T1 N2b M0
  T2 N2 M0
  T3 N1-N2a M0
  T4a N1 M0
C T3 N2b M0
  T4a N2 M0
  T4b N1-2 M0
IV A Any T Any N M1a
B Any T Any N M1b
C Any T Any N M1c

Colon Cancer – Treatment

Initial Management

  • Surgery is the Mainstay of Treatment
  • Criteria that Endoscopic Excision is Sufficient: Mn
    • T1 (< T2)
    • > 2 mm Margin
    • Well Differentiated
    • No Vascular or Lymphatic Invasion
  • Complicated Presentation:
    • Presenting with Obstruction: Consider Oncologic Resection vs Temporization with Delayed Elective Surgery
      • Temporizing Options:
        • Loop Transverse Colostomy
        • Colonic Stent
    • Presenting with Perforation: Normal Oncologic Resection with Complete Mesocolic Excision
      • Strongly Consider Ostomy

Treatment Approach

  • Stage I-II: Resection
    • T4b: Resect en Bloc with Portion of the Adjacent Organ
    • Consider Adjuvant Chemo for High-Risk Stage II (Excluded if MSI-H or dMMR – Good Prognosis)
      • Perforation or Obstruction
      • T4 Lesion
      • Indeterminate or Positive Margins
      • Poorly Differentiated/Undifferentiated
      • Lymphovascular or Perineural Invasion
      • Non-Oncologic Resection (< 12 LN)
  • Stage III: Resection & Adjuvant Chemo
  • Stage IV:
    • Resectable (Isolated Lung/Liver) – Resection & Adjuvant Chemo
      • Consider Neoadjuvant Chemo
    • Isolated Peritoneal Mets: Controversial
    • Unresectable – Definitive Chemotherapy with/without Immunotherapy
      • Asymptomatic: Avoid Surgery
      • Symptomatic: Consider Palliative Resection, Stenting or Diverting Ostomy
      • *Resect if Downstaged to Resectable
  • *Consider Neoadjuvant Chemotherapy for:
    • Clinical T4b Lesions
    • Bulky Nodal Disease
    • Metastases

Colon Resection

  • Bowel Prep: Mechanical & Oral ABX
    • Lower Rates of Surgical Site Infections, Anastomotic Leaks, Length of Stay & Readmission
  • Resection
    • Laparoscopic/MIS Preferred if Able
    • Extent:
    • Margin: 5 cm
    • Complete Mesocolic Excision
      • Remove Tumor En Bloc with Mesocolon & Regional Lymphadenectomy
      • Resect Mesentery Back to the Primary Vessel Origin
      • Oncologic Resection Requires: 12 Lymph Nodes
  • Appendix – Right Hemicolectomy Indications:
    • Appendix Adenocarcinoma (No Matter Size)
    • Appendix Mucinous Tumor If:
      • Moderate-Poor Differentiation
      • Not Completely Resected
      • Ruptured
      • *Well Differentiated, Not Ruptured & Completely Resected are Debated – It Appears that NOT Preforming a Completion Right Hemicolectomy Has Similar Survival with Low Rates of Lymph Node Involvement
    • Carcinoid Tumor

Chemotherapy Regimens

  • FOLFOX – Leucovorin (Folinic Acid), 5-FU (Fluorouracil) & Oxaliplatin
  • CAPEOX – Capecitabine & Oxaliplatin
  • Other Regimens (Category 2B):
    • FOLFIRI – Leucovorin (Folinic Acid), 5-FU (Fluorouracil) & Irinotecan
    • FOLFOXIRI – FOLFOX + Irinotecan

Immunotherapy Options

  • Bevacizumab (Avastin) – Vascular Endothelial Growth Factor (VEGF) Monoclonal Ab
  • Cetuximab – Epidermal Growth Factor Receptor (EGFR) Monoclonal Ab
  • Panitumumab – Epidermal Growth Factor Receptor (EGFR) Monoclonal Ab

Radiation Therapy (XRT)

  • None in Colon CA – Risk Damage to Surrounding Viscera
  • May Be Used in Rectal CA

Mnemonics

Criteria that Endoscopic Excision is Sufficient for Colon Cancer

  • #2 Stools: Size < T2 & Margin > 2 mm

References

  1. Yamauchi T, Shida D, Tanizawa T, Inada K. Anastomotic Recurrence of Sigmoid Colon Cancer over Five Years after Surgery. Case Rep Gastroenterol. 2013 Oct 17;7(3):462-6.(License: CC BY-NC-3.0)
  2. Samir at English Wikipedia. Wikimedia Commons. (License: CC BY-SA-3.0)