Colorectal Cancer

See Also

Epidemiology

Accounts for 8.5% of all new cancer cases
1. Third most common cancer and cancer death in the U.S.
In U.S. (2023)
1. Prevalence: 1.2 Million
2. Incidence: 153,000/year
3. Mortality: 52,000/year
Highest Incidence of Colon Cancer
1. North America
2. Western Europe
3. Australia and New Zealand
4. Japan
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
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)
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
References
1. Siegel (2023) CA Cancer J Clin 73(3):233-54 +PMID: 36856579 [PubMed]

Risk Factors

See Colon Cancer Risk Factors

Pathophysiology

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%)
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
Histologic Types
1. Colon Adenocarcinoma (>90% of cases)
2. Neuroendocrine tumors
3. Gastrointestinal stromal tumors
4. Lymphomas

Symptoms

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

Signs

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

Labs

Complete Blood Count
Serum Iron, Iron Saturation and Serum Ferritin
Comprehensive metabolic panel (serum Electrolytes, Liver Function Tests, Renal Function tests)
Coagulation studies (INR, PTT)
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

Differential Diagnosis

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

Diagnostics

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
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
MRI Abdomen
1. Indicated in suspected liver metastases or CT iodinated contrast allergy

Staging
TNM (AJCC/UICC 2017)

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
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
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
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)

Management

Endoscopic resection of pedunculated polyps without high risk features
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)
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]

Prevention

Primary prevention
1. See Colorectal Cancer Prevention
2. See Colorectal Cancer Screening
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

Course

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
Recurrence risk
1. Highest risk within first 5 years post-resection (17 to 42%)

Complications
General

Colorectal Cancer recurrence (typically in first 5 years after treatment)
Second primary Colorectal Cancer
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
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)

Complications
Gastrointestinal adverse effects

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

Protocol
Cancer Survivor Monitoring (post-Resection)

See Cancer Survivor Care
Oncology may often establish a survivorship care plan
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
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)
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
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)
References
1. Carek (2024) Am Fam Physician 110(1): 37-44 [PubMed]
2. Wilbur (2014) Am Fam Physician 91(1):29-36 [PubMed]

References

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