Colorectal Cancer

A comprehensive guide to understanding colorectal cancer, one of the most preventable yet common cancers

Overview

Colorectal cancer is cancer that begins in the colon or rectum, parts of the large intestine and digestive system. Often grouped together because of their many similarities, colon cancer and rectal cancer are the third most common cancer diagnosed in both men and women in the United States. Despite its prevalence, colorectal cancer is also one of the most preventable and treatable forms of cancer when detected early.

Most colorectal cancers begin as small, noncancerous (benign) clumps of cells called polyps that form on the inner lining of the colon or rectum. Over time, some of these polyps can become cancerous. This transformation typically takes 10-15 years, providing a significant window of opportunity for prevention through screening and polyp removal. Regular screening can detect these polyps before they become cancerous or find cancer in its early stages when treatment is most effective.

The American Cancer Society estimates that about 153,000 new cases of colorectal cancer are diagnosed annually in the United States, with approximately 52,000 deaths. However, both incidence and death rates have been declining in older adults due to increased screening and improvements in treatment. Concerningly, rates are rising in younger adults, with cases in people under 50 increasing by about 2% per year since the mid-1990s.

The location of the cancer within the colon or rectum can affect symptoms, treatment options, and prognosis. About 70% of colorectal cancers occur in the colon, while 30% occur in the rectum. Understanding the differences and similarities between these locations is important for appropriate management and treatment planning.

Symptoms

Colorectal cancer symptoms can be subtle and may not appear until the disease is advanced. Many symptoms can also be caused by other conditions, making awareness and appropriate screening crucial.

Rectal Bleeding

Bright red or dark blood in stool, on toilet paper, or in the toilet bowl. May be mistaken for hemorrhoids but should always be evaluated.

Change in Bowel Habits

Persistent diarrhea, constipation, or change in stool consistency lasting more than a few days. Stools may become narrow or pencil-thin.

Abdominal Discomfort

Persistent abdominal pain, cramps, gas, or feeling of fullness or bloating. Pain may be more pronounced after eating.

Unexplained Weight Loss

Losing weight without trying, often accompanied by loss of appetite. May indicate advanced disease affecting metabolism.

Fatigue and Weakness

Extreme tiredness that doesn't improve with rest. Often due to anemia from chronic blood loss or cancer's metabolic effects.

Incomplete Evacuation

Feeling that the bowel doesn't empty completely after a bowel movement. More common with rectal cancer.

Location-Specific Symptoms

Right-Sided Colon Cancer

  • Iron deficiency anemia
  • Fatigue and weakness
  • Abdominal pain
  • Hidden blood in stool
  • Often diagnosed later

Left-Sided Colon Cancer

  • Changes in bowel habits
  • Blood in stool
  • Constipation or diarrhea
  • Narrow stools
  • Abdominal cramping

Rectal Cancer

  • Rectal bleeding
  • Feeling of incomplete evacuation
  • Tenesmus (urge to defecate)
  • Change in stool caliber
  • Pelvic pain

Important: Early-stage colorectal cancer often has no symptoms. This is why screening is crucial for early detection. Don't wait for symptoms to appear before getting screened.

Causes

Colorectal cancer develops when cells in the colon or rectum mutate and grow uncontrollably. While the exact cause isn't always clear, researchers have identified several factors that contribute to its development.

The Development Process

  1. Normal cells: Healthy cells grow and divide in an orderly way
  2. DNA damage: Mutations occur in the DNA of colon or rectal cells
  3. Polyp formation: Abnormal cells form polyps on the inner lining
  4. Adenomatous polyps: Some polyps become precancerous
  5. Carcinoma in situ: Cancer cells form but haven't spread
  6. Invasive cancer: Cancer penetrates the colon or rectal wall
  7. Metastasis: Cancer spreads to lymph nodes or distant organs

Genetic Mutations

Key genetic changes in colorectal cancer development:

  • APC gene: Tumor suppressor gene mutated in 80% of colorectal cancers
  • KRAS: Oncogene mutated in 40-50% of cases
  • TP53: Tumor suppressor gene often lost late in progression
  • PIK3CA: Involved in cell growth and survival
  • Microsatellite instability (MSI): DNA mismatch repair deficiency

Types of Colorectal Cancer

  • Sporadic (70%): No family history, develops from acquired mutations
  • Familial (20%): Family history but no identified genetic syndrome
  • Hereditary (5-10%): Inherited genetic syndromes like Lynch syndrome, FAP

Contributing Factors

  • Chronic inflammation from inflammatory bowel disease
  • Diet high in processed meats and low in fiber
  • Bacterial imbalances in the gut microbiome
  • Insulin resistance and metabolic syndrome
  • Environmental carcinogens

Risk Factors

Understanding risk factors helps identify who should be screened earlier or more frequently for colorectal cancer.

Non-Modifiable Risk Factors

  • Age: Risk increases significantly after age 50
  • Personal history: Previous colorectal cancer or polyps
  • Family history: First-degree relatives with colorectal cancer
  • Hereditary syndromes:
    • Lynch syndrome (HNPCC)
    • Familial adenomatous polyposis (FAP)
    • MUTYH-associated polyposis
    • Peutz-Jeghers syndrome
  • Race: African Americans have highest incidence and mortality
  • Inflammatory bowel disease: Crohn's disease or ulcerative colitis

Modifiable Risk Factors

  • Diet: High in red and processed meats, low in fiber
  • Physical inactivity: Sedentary lifestyle
  • Obesity: Especially abdominal obesity
  • Smoking: Long-term tobacco use
  • Heavy alcohol use: More than 2 drinks per day
  • Type 2 diabetes: Insulin resistance
  • Night shift work: Circadian rhythm disruption

Risk Assessment Categories

Average Risk
Age 45+ with no other risk factors
Increased Risk
Family history, previous polyps, or IBD
High Risk
Hereditary cancer syndromes or multiple family members affected

Protective Factors

  • Regular screening and polyp removal
  • Physical activity
  • Diet high in fruits, vegetables, and whole grains
  • Adequate calcium and vitamin D
  • Aspirin (in certain individuals)
  • Hormone replacement therapy (postmenopausal women)

Types of Colorectal Cancer

Understanding the different types helps guide treatment decisions and prognosis.

By Cell Type

  • Adenocarcinoma (95%): Arises from glandular cells lining the colon/rectum
  • Carcinoid tumors: Slow-growing neuroendocrine tumors
  • Gastrointestinal stromal tumors (GISTs): Arise from specialized cells
  • Lymphomas: Cancer of immune system cells
  • Sarcomas: Arise from blood vessels, muscle, or connective tissue

By Molecular Subtype

Microsatellite Stable (MSS)

85% of cases. Chromosomal instability pathway. May benefit from standard chemotherapy.

Microsatellite Instable (MSI-H)

15% of cases. Defective DNA mismatch repair. Better prognosis, responds to immunotherapy.

CpG Island Methylator Phenotype (CIMP)

Hypermethylation of CpG islands. Often right-sided, may have BRAF mutations.

Hereditary Colorectal Cancer Syndromes

  • Lynch Syndrome:
    • 3-5% of colorectal cancers
    • Mutations in MLH1, MSH2, MSH6, PMS2, EPCAM
    • 80% lifetime risk of colorectal cancer
  • Familial Adenomatous Polyposis (FAP):
    • 1% of colorectal cancers
    • APC gene mutation
    • Hundreds to thousands of polyps
    • Nearly 100% cancer risk without treatment

Screening

Regular screening is the most powerful tool for preventing colorectal cancer. It can detect precancerous polyps for removal and find cancer early when treatment is most effective.

Screening Guidelines

  • Average risk: Begin screening at age 45
  • Family history: Begin at age 40 or 10 years before youngest case in family
  • Hereditary syndromes: May begin in teens or twenties
  • IBD: Begin 8-10 years after diagnosis

Screening Methods

Colonoscopy

  • Gold standard screening method
  • Every 10 years if normal
  • Can remove polyps during procedure
  • Requires bowel preparation
  • Sedation typically used

Stool-Based Tests

  • FIT: Annual fecal immunochemical test
  • gFOBT: Annual guaiac-based test
  • mt-sDNA: Multi-target stool DNA every 3 years
  • Non-invasive
  • Positive results require colonoscopy

Flexible Sigmoidoscopy

  • Every 5 years
  • Examines rectum and lower colon
  • No sedation needed
  • May miss right-sided cancers

CT Colonography

  • Virtual colonoscopy every 5 years
  • Less invasive than colonoscopy
  • Still requires bowel prep
  • Cannot remove polyps

Quality Indicators

  • Adenoma detection rate (ADR) >25%
  • Cecal intubation rate >95%
  • Adequate bowel preparation
  • Appropriate surveillance intervals

Diagnosis

Accurate diagnosis involves confirming the presence of cancer, determining its extent, and gathering information to guide treatment.

Diagnostic Tests

  1. Colonoscopy with biopsy: Definitive diagnosis through tissue sampling
  2. Blood tests:
    • Complete blood count (check for anemia)
    • Liver function tests
    • CEA (carcinoembryonic antigen) - baseline level
  3. Imaging studies:
    • CT scan of chest, abdomen, pelvis
    • MRI for rectal cancer staging
    • PET scan for unclear metastases

Pathology Assessment

  • Histologic type: Usually adenocarcinoma
  • Grade: Well, moderately, or poorly differentiated
  • Molecular testing:
    • Microsatellite instability (MSI)
    • KRAS/NRAS mutations
    • BRAF mutations
    • HER2 amplification

Additional Testing

  • Endorectal ultrasound: For rectal cancer depth assessment
  • Genetic counseling/testing: For suspected hereditary syndromes
  • Tumor profiling: For advanced disease treatment planning

Staging

Staging determines the extent of cancer spread and guides treatment decisions. Colorectal cancer uses the TNM system.

TNM Classification

  • T (Tumor):
    • Tis: Carcinoma in situ
    • T1: Invades submucosa
    • T2: Invades muscularis propria
    • T3: Invades through muscularis propria
    • T4: Penetrates visceral peritoneum or invades other organs
  • N (Nodes):
    • N0: No lymph node involvement
    • N1: 1-3 lymph nodes involved
    • N2: 4 or more lymph nodes involved
  • M (Metastasis):
    • M0: No distant metastasis
    • M1: Distant metastasis present

Stage Groupings

Stage 0
Tis, N0, M0 - Cancer in situ
Stage I
T1-T2, N0, M0 - Early cancer confined to colon wall
Stage II
T3-T4, N0, M0 - Locally advanced, no lymph nodes
Stage III
Any T, N1-N2, M0 - Lymph node involvement
Stage IV
Any T, Any N, M1 - Distant metastasis

Prognostic Factors

  • Number of lymph nodes examined (minimum 12)
  • Lymphovascular invasion
  • Perineural invasion
  • Tumor budding
  • MSI status
  • BRAF mutation status

Treatment

Treatment depends on cancer stage, location, molecular characteristics, and patient factors. A multidisciplinary approach provides the best outcomes.

Surgery

Colon Cancer Surgery

  • Colectomy (partial colon removal)
  • Lymph node dissection
  • Minimally invasive options available
  • Primary anastomosis usually possible

Rectal Cancer Surgery

  • Low anterior resection (LAR)
  • Abdominoperineal resection (APR)
  • Total mesorectal excision (TME)
  • May require temporary or permanent colostomy

Local Excision

  • For early-stage rectal cancer
  • Transanal excision
  • Transanal endoscopic microsurgery (TEM)
  • Preserves sphincter function

Chemotherapy

  • Adjuvant (after surgery):
    • FOLFOX (5-FU, leucovorin, oxaliplatin)
    • CAPOX (capecitabine, oxaliplatin)
    • Duration: 3-6 months
  • Neoadjuvant (before surgery):
    • For rectal cancer with radiation
    • May downstage tumors
  • Metastatic disease:
    • FOLFIRI (5-FU, leucovorin, irinotecan)
    • FOLFOXIRI for fit patients

Radiation Therapy

  • Primarily for rectal cancer:
    • Short course (5 days) or long course (5-6 weeks)
    • Combined with chemotherapy
    • Reduces local recurrence
  • Indications:
    • T3-T4 tumors
    • Node-positive disease
    • Close to circumferential margin

Targeted Therapy

Anti-VEGF Therapy

  • Bevacizumab (Avastin)
  • Ramucirumab (Cyramza)
  • Aflibercept (Zaltrap)

Anti-EGFR Therapy

  • Cetuximab (Erbitux)
  • Panitumumab (Vectibix)
  • Only for RAS wild-type tumors

Other Targeted Agents

  • Regorafenib (Stivarga)
  • Trifluridine/tipiracil (Lonsurf)
  • Encorafenib + cetuximab (BRAF V600E)

Immunotherapy

  • For MSI-H/dMMR tumors:
    • Pembrolizumab (Keytruda)
    • Nivolumab (Opdivo) ± ipilimumab
    • Dostarlimab (Jemperli)
  • Clinical trials: Combinations and novel agents

Prevention

Many colorectal cancers can be prevented through lifestyle modifications and screening.

Primary Prevention

  • Diet:
    • Increase fiber intake (25-30g daily)
    • Limit red meat (<18 oz/week)
    • Avoid processed meats
    • Eat plenty of fruits and vegetables
    • Choose whole grains
  • Physical activity: At least 150 minutes moderate exercise weekly
  • Weight management: Maintain healthy BMI
  • Avoid tobacco: Don't smoke or use tobacco products
  • Limit alcohol: No more than 1-2 drinks per day

Chemoprevention

  • Aspirin: May reduce risk in certain individuals
  • NSAIDs: Some protective effect but not routinely recommended
  • Calcium and vitamin D: Modest protective effect
  • Folic acid: Mixed evidence

Secondary Prevention

  • Regular screening according to guidelines
  • Polyp removal during colonoscopy
  • Surveillance for high-risk individuals
  • Genetic counseling and testing when indicated

For High-Risk Individuals

  • Earlier and more frequent screening
  • Consider prophylactic surgery for FAP
  • Chemoprevention trials
  • Lifestyle modifications especially important

Prognosis

Survival rates have improved significantly due to better screening, surgical techniques, and systemic therapies.

5-Year Survival Rates

  • Localized (Stage I-II): 90%
  • Regional (Stage III): 72%
  • Distant (Stage IV): 14%
  • Overall: 65%

Factors Affecting Prognosis

  • Stage at diagnosis (most important)
  • Tumor location (rectal vs colon)
  • Histologic grade
  • MSI status (MSI-H has better prognosis)
  • Number of lymph nodes involved
  • Completeness of surgical resection
  • Response to treatment
  • Patient age and overall health

Oligometastatic Disease

Selected patients with limited metastases may achieve long-term survival or cure:

  • Resectable liver metastases: 40-50% 5-year survival
  • Resectable lung metastases: 30-40% 5-year survival
  • Combination of surgery and systemic therapy

Note: These statistics are averages. Individual prognosis depends on many factors. Discuss your specific situation with your oncology team.

When to See a Doctor

Early detection improves outcomes. Don't delay seeking medical attention for concerning symptoms.

See Your Doctor For

  • Blood in stool or on toilet paper
  • Change in bowel habits lasting more than a few days
  • Persistent abdominal discomfort
  • Unexplained weight loss
  • Persistent fatigue or weakness
  • Feeling that bowel doesn't empty completely
  • Iron deficiency anemia

Screening Reminders

  • Average risk: Begin screening at age 45
  • Family history: May need earlier screening
  • Symptoms at any age warrant evaluation
  • Don't skip screening due to lack of symptoms

Seek immediate care for:

  • Severe abdominal pain
  • Signs of bowel obstruction (no bowel movements, vomiting, distension)
  • Heavy rectal bleeding
  • Severe weakness or dizziness

Follow-up Care

After treatment, regular follow-up is crucial:

  • Physical exams every 3-6 months for first 2 years
  • CEA levels if initially elevated
  • CT scans annually for 3-5 years
  • Colonoscopy 1 year after surgery, then per guidelines

Medical Disclaimer: This information is for educational purposes only and should not replace professional medical advice. Always consult with a qualified healthcare provider for diagnosis and treatment of any medical condition.