Colorectal Cancer: Complete Guide

Written by: Robert Thompson, MD

Reviewed by: Dr. Lisa Chen, Gastroenterologic Oncologist

Last reviewed: January 24, 2026

Quick Facts

Third most common cancer worldwide
Second leading cause of cancer death
90% of cases occur in people over age 50
Highly preventable through screening
5-year survival rate is 65% overall, 91% when caught early
Most colorectal cancers start as polyps
Screening can prevent cancer by removing precancerous polyps

What is Colorectal Cancer?

Colorectal cancer is cancer that starts in the colon or rectum, which are parts of the large intestine in the digestive system. The colon is about 5 feet long and absorbs water and nutrients from food. The rectum is the last 6 inches of the large intestine, connecting to the anus.

Key Points

Most colorectal cancers (95%) are adenocarcinomas
Usually develops slowly over 10-15 years
Often starts as a polyp (growth on inner lining)
Can be prevented by removing polyps before they become cancerous
Early-stage colorectal cancer often has no symptoms

Anatomy of the Colon and Rectum

The large intestine consists of:

Cecum: Beginning of the colon, connects to small intestine
Ascending colon: Right side, travels upward
Transverse colon: Crosses the abdomen
Descending colon: Left side, travels downward
Sigmoid colon: S-shaped section before rectum
Rectum: Final 6 inches before anus

Types and Location

By Histology

Adenocarcinoma (95%): Starts in mucus-producing gland cells
Carcinoid tumors (1%): Neuroendocrine tumors
Gastrointestinal stromal tumors (GISTs): Rare, start in interstitial cells
Lymphomas: Start in immune system cells
Sarcomas: Start in blood vessels or connective tissue

By Location

Right-sided (proximal) colon cancer (25%): Cecum, ascending colon
- Often presents with anemia
- Less likely to cause obstruction
- May have worse prognosis
Left-sided (distal) colon cancer (40%): Descending, sigmoid colon
- More likely to cause changes in bowel habits
- Blood more visible in stool
- Higher risk of obstruction
Rectal cancer (35%): Within 15 cm of anal verge
- May require different treatment approach
- Often needs radiation therapy
- Sphincter preservation important consideration

Hereditary Colorectal Cancer Syndromes

Lynch Syndrome (3-5%): Most common hereditary CRC syndrome
Familial Adenomatous Polyposis (FAP) (<1%): Hundreds to thousands of polyps
MUTYH-Associated Polyposis (MAP): Multiple adenomatous polyps
Peutz-Jeghers Syndrome: Hamartomatous polyps
Juvenile Polyposis Syndrome: Multiple juvenile polyps

Signs and Symptoms

Early Warning Signs

Change in bowel habits lasting more than a few days
- Diarrhea
- Constipation
- Narrowing of stool
Blood in or on the stool (bright red or very dark)
Persistent abdominal discomfort
- Cramps
- Gas
- Pain
- Bloating
Feeling that bowel doesn't empty completely
Weakness or fatigue
Unexplained weight loss

Advanced Symptoms

Iron deficiency anemia
Bowel obstruction (severe constipation, vomiting)
Bowel perforation (severe pain, fever)
Jaundice (if spread to liver)
Shortness of breath (if spread to lungs)
Bone pain (if spread to bones)

⚠️ Seek Immediate Medical Attention If:

Severe abdominal pain with fever
Heavy rectal bleeding
Signs of bowel obstruction (no gas/stool passage, vomiting, distended abdomen)
Signs of perforation (sudden severe pain, rigid abdomen)

Location-Specific Symptoms

Right colon: Fatigue, weakness, anemia (often no visible blood)
Left colon: Changes in bowel habits, visible blood, obstruction
Rectum: Rectal bleeding, tenesmus (feeling of incomplete evacuation), pain

Causes and Risk Factors

Non-Modifiable Risk Factors

Age: 90% of cases occur after age 50
Personal history:
- Previous colorectal cancer or polyps
- Inflammatory bowel disease (IBD)
  - Ulcerative colitis
  - Crohn's disease
Family history:
- First-degree relative with CRC (doubles risk)
- Multiple relatives or diagnosis before age 50 (higher risk)
Hereditary syndromes: Lynch syndrome, FAP, others
Race/ethnicity: Higher rates in African Americans
Type 2 diabetes: 30% increased risk

Modifiable Risk Factors

Diet:
- High red meat consumption (>100g/day)
- Processed meats
- Low fiber intake
- Low calcium intake
Physical inactivity: 25% increased risk
Obesity: 30% increased risk
Smoking: 20% increased risk
Heavy alcohol use: >2-3 drinks/day increases risk

Protective Factors

Regular physical activity
High-fiber diet
Adequate calcium and vitamin D
Aspirin (in certain individuals)
Hormone replacement therapy (postmenopausal women)

Screening Guidelines

🔍 Current USPSTF Recommendations (2021)

Average-risk individuals: Begin screening at age 45

Continue until: Age 75 (76-85: individualized decision)

Screening Options for Average-Risk Individuals

Stool-Based Tests

FIT (Fecal Immunochemical Test): Annually
- Detects blood in stool
- No dietary restrictions
- Sensitivity: 74-80% for cancer
gFOBT (Guaiac Fecal Occult Blood Test): Annually
- Requires dietary restrictions
- Less specific than FIT
Stool DNA Test (Cologuard): Every 3 years
- Combines FIT with DNA markers
- Sensitivity: 92% for cancer, 42% for advanced adenomas

Direct Visualization Tests

Colonoscopy: Every 10 years
- Gold standard
- Can remove polyps during procedure
- Examines entire colon
CT Colonography (Virtual Colonoscopy): Every 5 years
- Non-invasive imaging
- Requires bowel prep
- Polyps require follow-up colonoscopy
Flexible Sigmoidoscopy: Every 5 years (or 10 with annual FIT)
- Examines lower third of colon
- Less prep than colonoscopy

High-Risk Screening

Family history of CRC or advanced polyps: Begin at age 40 or 10 years before youngest case
Lynch syndrome: Begin at age 20-25, colonoscopy every 1-2 years
FAP: Begin at age 10-12, annual flexible sigmoidoscopy
IBD: Begin 8 years after diagnosis, colonoscopy every 1-3 years

Diagnosis

Diagnostic Workup

Medical history and physical exam: Including digital rectal exam
Laboratory tests:
- Complete blood count (check for anemia)
- Liver function tests
- CEA (carcinoembryonic antigen) - baseline for monitoring

Colonoscopy and Biopsy

Direct visualization of entire colon
Tissue biopsy for pathological confirmation
Can remove small polyps completely
Tattooing of tumor location for surgery

Imaging Studies

CT scan (chest, abdomen, pelvis): Staging, detect metastases
MRI: Particularly important for rectal cancer staging
PET scan: For unclear findings or recurrence
Endoscopic ultrasound: Rectal cancer depth assessment

Molecular Testing

Important for treatment decisions:

Microsatellite instability (MSI) or mismatch repair (MMR): All patients
RAS mutations (KRAS/NRAS): For metastatic disease
BRAF V600E mutation: Prognostic and treatment implications
HER2 amplification: In RAS/BRAF wild-type tumors
NTRK fusions: Rare but targetable

Staging

TNM Staging System

Stage	Description	5-Year Survival
Stage 0	Carcinoma in situ, confined to mucosa	~95%
Stage I	Tumor invades submucosa or muscle, no lymph nodes	90-92%
Stage IIA	Tumor through muscle, no lymph nodes	87%
Stage IIB	Tumor through serosa, no lymph nodes	83%
Stage IIC	Tumor invades nearby organs, no lymph nodes	79%
Stage IIIA	Early tumor, 1-3 lymph nodes OR through muscle, 1 node	89%
Stage IIIB	Various combinations, 1-3 nodes involved	69-80%
Stage IIIC	4+ lymph nodes involved	53%
Stage IVA	Spread to 1 distant organ	14%
Stage IVB	Spread to 2+ distant organs	11%
Stage IVC	Peritoneal metastases	8%

Treatment Options

Surgery

For Colon Cancer

Polypectomy: Removal during colonoscopy (early stage)
Local excision: Removal of small cancers
Colectomy: Removal of cancer and margins
- Right hemicolectomy
- Left hemicolectomy
- Sigmoid colectomy
- Total colectomy (rare)
Lymph node dissection: Minimum 12 nodes examined

For Rectal Cancer

Local excision: For early tumors
Low anterior resection (LAR): Preserves sphincter
Abdominoperineal resection (APR): Permanent colostomy
Total mesorectal excision (TME): Standard technique

Radiation Therapy

Primarily for rectal cancer:

Neoadjuvant (before surgery): Shrink tumor, improve resectability
Short course: 5 Gy × 5 fractions
Long course: 45-50.4 Gy with chemotherapy
Adjuvant (after surgery): If not given preoperatively

Chemotherapy

Adjuvant Chemotherapy (Stage II-III)

FOLFOX: 5-FU + leucovorin + oxaliplatin (standard)
CAPOX: Capecitabine + oxaliplatin
5-FU/leucovorin: For patients who can't tolerate oxaliplatin
Capecitabine monotherapy: Oral option

Metastatic Disease

First-line combinations:
- FOLFOX or CAPOX
- FOLFIRI (5-FU + leucovorin + irinotecan)
- FOLFOXIRI (triplet therapy)
Second/third-line options:
- Regorafenib (Stivarga)
- Trifluridine/tipiracil (Lonsurf)

Targeted Therapy

Anti-VEGF Therapy

Bevacizumab (Avastin): First-line with chemotherapy
Ramucirumab (Cyramza): Second-line with FOLFIRI
Aflibercept (Zaltrap): Second-line with FOLFIRI

Anti-EGFR Therapy (RAS/BRAF Wild-Type)

Cetuximab (Erbitux): Left-sided tumors
Panitumumab (Vectibix): Left-sided tumors

Other Targeted Agents

Encorafenib (Braftovi) + Cetuximab: BRAF V600E-mutated
Larotrectinib (Vitrakvi): NTRK fusion-positive
Entrectinib (Rozlytrek): NTRK fusion-positive

Immunotherapy

For MSI-H/dMMR tumors (4% of metastatic CRC):

Pembrolizumab (Keytruda): First-line or later
Nivolumab (Opdivo): Alone or with ipilimumab
Dostarlimab (Jemperli): Second-line or later

Treatment by Stage

Stage 0-I: Surgery alone usually curative
Stage II: Surgery ± adjuvant chemotherapy (high-risk features)
Stage III: Surgery + adjuvant chemotherapy
Stage IV: Systemic therapy ± surgery for resectable metastases

Prognosis and Survival

Overall Survival Statistics

Overall 5-year survival: 65%
Localized disease: 91%
Regional spread: 72%
Distant metastases: 14%

Prognostic Factors

Favorable Factors

Early stage at diagnosis
MSI-H/dMMR status
Well-differentiated histology
Absence of lymphovascular invasion
Normal CEA levels
Good performance status

Unfavorable Factors

Advanced stage
BRAF V600E mutation
Right-sided primary tumor (controversial)
Poorly differentiated histology
Perineural invasion
Bowel obstruction or perforation at presentation
Elevated CEA levels

Oligometastatic Disease

Selected patients with limited metastases may achieve cure:

Liver-only metastases: 5-year survival 30-50% after resection
Lung-only metastases: Similar outcomes with resection
Combination of systemic therapy and local treatments

Prevention

Primary Prevention

Screening: Most effective prevention strategy
Lifestyle modifications:
- Maintain healthy weight
- Regular physical activity (150 minutes/week)
- Limit red meat (<500g/week)
- Avoid processed meats
- High-fiber diet (25-35g/day)
- Limit alcohol (≤1 drink/day women, ≤2 men)
- Don't smoke

Chemoprevention

Aspirin: May reduce risk by 20-30%
- USPSTF recommends for certain individuals age 50-59
- Consider cardiovascular benefits/risks
Calcium supplements: Modest risk reduction
Vitamin D: May reduce risk with adequate levels

For High-Risk Individuals

Enhanced surveillance
Genetic counseling and testing
Prophylactic surgery for hereditary syndromes
Aspirin for Lynch syndrome

Living with Colorectal Cancer

During Treatment

Managing chemotherapy side effects
- Neuropathy from oxaliplatin
- Diarrhea management
- Hand-foot syndrome
Nutritional support
Ostomy care and adjustment (if applicable)
Psychological support
Sexual health counseling

Follow-up Care

Years 1-2: Every 3-6 months
- Physical exam
- CEA levels
- CT scans
Years 3-5: Every 6 months
After 5 years: Annual follow-up
Colonoscopy: 1 year after surgery, then per findings

Survivorship Issues

Long-term bowel dysfunction
Oxaliplatin-induced neuropathy
Sexual and urinary dysfunction (especially rectal cancer)
Body image concerns (ostomy)
Fear of recurrence
Return to work considerations

Frequently Asked Questions

At what age should I start screening?

Average-risk individuals should begin screening at age 45. Those with family history or other risk factors may need to start earlier. African Americans may benefit from starting at age 45 regardless of other risk factors.

Is colorectal cancer hereditary?

About 5-10% of colorectal cancers are hereditary (Lynch syndrome, FAP). Another 20-30% have familial clustering. Having a first-degree relative with CRC doubles your risk.

How often do polyps become cancerous?

Most polyps (95%) never become cancer. Adenomatous polyps have about a 5-10% chance of becoming cancerous over 10-15 years. Size matters: polyps >1cm have higher risk.

Can colorectal cancer be prevented?

Yes! Up to 70% of colorectal cancers could be prevented through screening (removing polyps), healthy lifestyle, and risk factor modification.

What's the difference between colon and rectal cancer treatment?

Rectal cancer often requires radiation therapy before or after surgery due to the rectum's location in the pelvis. Surgery for rectal cancer may be more complex to preserve sphincter function.

How accurate are stool tests for screening?

FIT detects about 74-80% of cancers and 23% of advanced adenomas. Stool DNA tests detect 92% of cancers and 42% of advanced adenomas. Colonoscopy remains the gold standard.

Will I need a colostomy?

Most patients don't need permanent colostomy. It's mainly required for very low rectal cancers near the anus. Temporary ostomies may be used to protect healing anastomoses.

What is MSI-H and why does it matter?

MSI-H (microsatellite instability-high) occurs in 15% of colorectal cancers. These tumors respond exceptionally well to immunotherapy and generally have better prognosis.

Sources

National Cancer Institute. Colorectal Cancer Treatment (PDQ) - Health Professional Version. Updated January 2026.
American Cancer Society. Colorectal Cancer Facts & Figures 2024-2026.
NCCN Clinical Practice Guidelines. Colon Cancer. Version 1.2026.
US Preventive Services Task Force. Colorectal Cancer Screening Recommendation. JAMA. 2021.
Siegel RL, et al. Colorectal Cancer Statistics, 2026. CA Cancer J Clin. 2026.
ASCO Guidelines. Treatment of Metastatic Colorectal Cancer. 2025.
ACG Clinical Guidelines: Colorectal Cancer Screening. Am J Gastroenterol. 2025.