Colorectal Cancer

Aka: Colorectal Cancer, Colon Cancer, Colon Carcinoma, Colorectal Carcinoma

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II. Epidemiology

  1. Accounts for 8.5% of all new cancer cases
    1. Third most common cancer and cancer death in the U.S.
  2. In U.S. (2023)
    1. Prevalence: 1.2 Million
    2. Incidence: 153,000/year
    3. Mortality: 52,000/year
  3. Highest Incidence of Colon Cancer
    1. North America
    2. Western Europe
    3. Australia and New Zealand
    4. Japan
  4. Age
    1. Median age of sporadic Colorectal Cancer: 65 years old
    2. Significant increases in onset age <50 years (and at more advanced stages, higher mortality)
    3. Younger native americans and african americans have seen some of the greatest increases in Incidence
  5. Gender
    1. More common in men by a slight margin (53%)
    2. Men have onset at a younger age (68 years, rather than 72 years)
  6. Heredity
    1. See Colon Cancer Risk Factors
    2. Sporadic Colorectal Cancer (unrelated to Family History) in 70% of patients
    3. Colorectal Cancer with strong Family History in 20 to 25% of patients
    4. Inherited genetic mutation (e.g. Lynch Syndrome) is identified in 3 to 5% of patients
  7. References
    1. Siegel (2023) CA Cancer J Clin 73(3):233-54 +PMID: 36856579 [PubMed]

III. Risk Factors

  1. See Colon Cancer Risk Factors

IV. Pathophysiology

  1. Distribution
    1. Rectal Lesions (20-30%)
    2. Colonic Lesions (70%)
      1. Sigmoid Colon (55%)
      2. Ascending Colon (23%)
      3. Cecum (8%)
      4. Transverse Colon (8%)
      5. Descending Colon (8%)
  2. Dysplasia develops overtime with accumulating genetic mutations via 3 different mechanisms
    1. Chromosomal instability with adenoma to carcinoma development via mutations (e.g. APC, KRAS)
    2. MMR DNA Replication errors via genetic mutations (e.g. MLH1, MSH2, PMS2)
    3. CpG Island Methylator Phenotype (CIMP) associated with serrated polyps, and with KRAS and BRAF mutations
  3. Histologic Types
    1. Colon Adenocarcinoma (>90% of cases)
    2. Neuroendocrine tumors
    3. Gastrointestinal stromal tumors
    4. Lymphomas

V. Symptoms

  1. Typically asymptomatic when found on screening Colonoscopy
  2. Rectal Bleeding
  3. Abdominal Pain
  4. Anemia (esp. right sided lesions)
  5. Constipation (esp. left sided lesions)
  6. Surgical Abdomen presentations (e.g. acute obstruction, bowel perforation)

VI. Signs

  1. Palpable abdominal masses
  2. Lymphadenopathy
  3. Hepatosplenomegaly
  4. Rectal Exam
    1. Palpable lesions
    2. Sphincter tone

VII. Labs

  1. Complete Blood Count
  2. Serum Iron, Iron Saturation and Serum Ferritin
  3. Comprehensive metabolic panel (serum Electrolytes, Liver Function Tests, Renal Function tests)
  4. Coagulation studies (INR, PTT)
  5. Carcinoembryonic Antigen (CEA)
    1. Most common Tumor Marker in Colorectal Cancer
    2. High initial CEA levels are associated with a worse prognosis
    3. Obtained at baseline, and if suspected recurrence

VIII. Differential Diagnosis

  1. See Lower Gastrointestinal Bleeding
  2. Inflammatory Bowel Disease (Crohns Disease, Ulcerative Colitis)
  3. Ischemic Bowel
  4. Other malignancies
    1. Carcinoid Tumor
    2. Small Bowel carcinoma
    3. Gastrointestinal Lymphoma

IX. Diagnostics

  1. Colonoscopy
    1. Indicated in all Colon Cancer patients
    2. Test Sensitivity: 94-95%
      1. May miss right sided, sessile or flat polyps
    3. Obtain multiple biopsies for tissue diagnosis
    4. Also, Tattoo peri-tumor colon for intraoperative identification
  2. CT Chest Abdomen and Pelvis with IV Contrast
    1. Indicated in all Colon Cancer patients
    2. Positron Emission CT (PET) may be indicated in some patients
  3. MRI Abdomen
    1. Indicated in suspected liver metastases or CT iodinated contrast allergy

X. Staging: TNM (AJCC/UICC 2017)

  1. Tumor (T)
    1. Tx: Tumor cannot be assessed
    2. T0: No tumor evidence
    3. Tis: Carcinoma in situ
    4. T1: Tumor invades submucosa (muscularis mucosa)
    5. T2: Tumor invades muscularis propria
    6. T3: Tumor invades pericolorectal tissue
    7. T4: Tumor invades visceral peritoneum or adheres to adjacent organ or structure
      1. T4a: Tumor invades visceral peritoneum
      2. T4b: Tumor adheres to adjacent organ or structure
  2. Lymph Node (N)
    1. Nx: Lymph Nodes not assessed
    2. N0: No regional Lymph Node involvement
    3. N1: 1 to 3 regional Lymph Nodes involved
      1. N1a: 1 regional Lymph Node positive
      2. N1b: 2-3 regional Lymph Nodes positive
      3. N1c: Tumor deposits on subserosa, mesentery, nonperitonealized pericolic, perirectal or mesorectal tissue
    4. N2: 4 or more regional Lymph Nodes positive
      1. N2a: 4 to 6 regional Lymph Nodes positive
      2. N2b: 7 or more regional Lymph Nodes positive
  3. Metastases (M)
    1. M0: No distant metastases
    2. M1: Distant Metastases
      1. M1a: Metastases to 1 site without peritoneal involvement
      2. M1b: Metastases to 2 sites without peritoneal involvement
      3. M1c: Metastases with peritoneal involvement
  4. Overall Staging
    1. Localized Disease
      1. Stage 0: TisN0M0
      2. Stage 1: T1-2N0M0 (74% five year survival)
    2. Regional disease
      1. Stage 2a: T3N0M0 (66% five year survival)
      2. Stage 2b: T4aN0M0 (58% five year survival)
      3. Stage 2c: T4bN0M0 (37% five year survival)
      4. Stage 3a-c: Progressions of T1-4, N1-2 and no metastases
        1. Divided over stages 3a, 3b and 3c with five year survivals at 73%, 46% and 28% respectively
    3. Distant Disease
      1. Stage 4a-c: Metastatic disease correlating with M1a, M1b and M1c (overall 5% five year survival)

XI. Management

  1. Endoscopic resection of pedunculated polyps without high risk features
  2. Most Colorectal Cancer is treated with surgery, augmented with chemoradiation and Biologic Agents
    1. Surgery based treatment is associated with >90% five year survival
      1. Surgical approaches are based on anatomic tumor location
      2. Radical surgery with lymphadenectomy followed by neoadjuvant Chemotherapy
      3. Palliative surgery followed by palliative Chemotherapy
    2. Chemotherapy
      1. Multiple Chemotherapy regimens (e.g. FOLFOX, FOLFIRI, CAPEOX)
      2. Muliple Chemotherapy agents are used (e.g. fluoruracil, Irinotecan, Oxaliplatin, raltitrexed)
    3. Radiation Therapy
      1. Primarily indicated in rectal cancer
    4. Monoclonal Antibody-Mediated Chemotherapy
      1. VEGFR Monoclonal Antibody (e.g. Bevacizumab)
      2. EGFR Monoclonal Antibody (e.g. Cetuximab)
    5. Immune Checkpoint Inhibitors
      1. PD-1 Monoclonal Antibody (Pembrolizumab)
  3. Non-resectable hepatic metastases
    1. Radiofrequency Ablation
      1. Small trials suggest prolonged survival or cure
      2. Wong (2001) Am J Surg 182:552-7 [PubMed]

XII. Prevention

  1. Primary prevention
    1. See Colorectal Cancer Prevention
    2. See Colorectal Cancer Screening
  2. Secondary prevention
    1. Routine screening for other cancers
    2. Tobacco Cessation
    3. Obesity Management and Healthy Diet (Colorectal Cancer risk factors)
    4. Exercise improves quality of life and decreases overall mortality (goal: 150 min/week)
    5. Daily low dose Aspirin

XIII. Course

  1. Five-year survival
    1. Surgically resectable Colorectal Cancer is associated with 5 year survival rates >90%
      1. Unresectable Colorectal Cancer is associated with 5 year survival rates of 10%
    2. Staging and regional involvement predict five year survival
      1. Localized disease: 90% five year survival
      2. Regional disease: 73% five year survival
      3. Distant disease: 13% five year survival
  2. Recurrence risk
    1. Highest risk within first 5 years post-resection (17 to 42%)

XIV. Complications: General

  1. Colorectal Cancer recurrence (typically in first 5 years after treatment)
  2. Second primary Colorectal Cancer
  3. Urinary symptoms
    1. Stress Incontinence
    2. Urge Incontinence
    3. Urology Consultation indications
      1. Persistent Urinary Retention (pelvic nerve injury is common in initial post-operative period)
      2. Persistent Hematuria
  4. Neuropsychiatric
    1. Cognitive dysfunction (Chemotherapy associated)
      1. Typically mild and transient
    2. Major Depression
    3. Anxiety Disorder
    4. Insomnia
    5. Sexual Dysfunction
      1. Vaginal Dryness and Dyspareunia in women
      2. Erectile Dysfunction (pelvic radiation, platinum-based Chemotherapy)
      3. Ostomy-related concerns
    6. Neuropathy (esp. platinum-based Chemotherapy such as Oxaliplatin)
      1. Duloxetine (Cymbalta)
      2. Gabapentin (Neurontin) or Pregabalin (Lyrica)
      3. Tricyclic Antidepressant
    7. Fatigue
      1. Common in Colorectal Cancer survivors
      2. Consider evaluating for alternative Fatigue cause (e.g Anemia, Hypothyroidism)

XV. Complications: Gastrointestinal adverse effects

  1. Ostomy care
  2. Diarrhea
    1. Dietary Fiber supplementation
    2. Probiotic supplementation
    3. Periodic Loperamide (Imodium) use
  3. Fecal Incontinence
    1. Periodic Loperamide (Imodium) use
    2. Methylcellulose and Dietary Fiber
    3. Biofeedback
  4. Radiation Proctitis (Diarrhea, bleeding)
    1. Endoscopic argon plasma coagulation
    2. Sucralfate enemas
    3. Hanson (2012) Dis Colon Rectum 55(10): 1081-95 [PubMed]
  5. Abdominal Pain
    1. Acute pain (esp. RUQ Pain, Pelvic Pain)
      1. Evaluate for cancer recurrence
    2. Chronic Pain
      1. Radiation Proctitis
      2. Incisional Hernia
  6. Pelvic Fracture
    1. Higher risk in women who undergo pelvic radiation

XVI. Protocol: Cancer Survivor Monitoring (post-Resection)

  1. See Cancer Survivor Care
  2. Oncology may often establish a survivorship care plan
  3. Follow-up visits (starting 4-5 weeks after curative resection)
    1. Visit every 3-6 months for 2-3 years, then every 6 months until 5 years post-resection
    2. May avoid in Stage I at low risk of recurrence
    3. Focus areas
      1. Ostomy problems or Stool Incontinence
      2. Radiation Proctitis
      3. Bowel adhesions
  4. Carcinoembryonic Antigen (CEA-125)
    1. Perform at each visit (every 3-6 months for 2-3 years, then every 6 months until 5 years post-resection)
    2. May avoid in Stage I at low risk of recurrence
    3. Other labs (e.g. CBC, Comprehensive panel) are not routinely indicated (unless other concerns)
  5. Colonoscopy
    1. Perform at one year post resection and resect new polyps
    2. Normal Colonoscopy
      1. Repeat at 3 years post-resection, and then every 5 years
    3. Advanced adenomatous polyp (>1 cm, high grade dysplasia or villous component)
      1. Repeat Colonoscopy in 1 year
    4. Obstructing lesion prevented Colonoscopy before resection
      1. Colonoscopy in 3 to 6 months, and then as above
    5. Rectal cancer at high risk of recurrence
      1. Flexible Sigmoidoscopy every 3-6 months for first 2-3 years post-resection
  6. Imaging
    1. PET scan is not recommended for recurrence monitoring
    2. CT Chest, Abdomen and Pelvis Indications (every 12 months for 5 years post-resection)
      1. Stage I or II if high risk for recurrence
      2. Stage III disease
      3. Stage IV disease (CT interval may be increased to coincide with CEA and visit timing)
  7. References
    1. Carek (2024) Am Fam Physician 110(1): 37-44 [PubMed]
    2. Wilbur (2014) Am Fam Physician 91(1):29-36 [PubMed]

XVII. References

  1. Duan in Morgado-Diaz (2022) Colorectal Cancer: An Overview, in Gastrointestinal Cancers, Exon Publications, Brisbane
    1. https://www.ncbi.nlm.nih.gov/books/NBK586003/
  2. Menon (2024) Colon Cancer, StatPearls, Treasure Island, FL
    1. https://www.ncbi.nlm.nih.gov/books/NBK470380/
  3. Burgers (2018) Am Fam Physician 97(5):331-6 [PubMed]
  4. Short (2014) Am Fam Physician 91(2): 93-100 [PubMed]
  5. Sunga (2005) Am Fam Physician 71:699-714 [PubMed]

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