Colorectal Cancer

Colorectal cancer includes cancers of the colon and rectum. Most are adenocarcinomas. Many develop through a multistep process from adenomatous polyps or serrated lesions, although not every polyp becomes cancer.

Colon and rectal cancers share many biological features, but surgery, radiation use, and preoperative treatment can differ substantially. A reliable educational site should not present their treatment pathways as identical.

• Blood in the stool, rectal bleeding, or dark stools
• A persistent change in bowel habits, including diarrhea, constipation, narrower stool, or a feeling of incomplete emptying
• Abdominal pain, bloating, or cramping
• Unexplained iron-deficiency anemia, fatigue, or shortness of breath
• Unexplained weight loss or reduced appetite
• Bowel obstruction with severe pain, vomiting, distention, and inability to pass stool or gas
• Rectal urgency, tenesmus, or pain with bowel movements in some rectal cancers

Early colorectal cancer may cause no symptoms, which is one reason screening matters.

• Increasing age
• A personal history of adenomas, serrated polyps, or colorectal cancer
• A family history of colorectal cancer or advanced polyps
• Lynch syndrome, familial adenomatous polyposis, and other inherited syndromes
• Long-standing and extensive inflammatory bowel disease
• Obesity and physical inactivity
• Smoking and higher alcohol intake
• Dietary patterns high in processed meat and, in some studies, red meat
• Type 2 diabetes may be associated with increased risk

Inherited risk can change the recommended starting age and interval for colonoscopy. Family history should be documented carefully.

• Many U.S. organizations recommend regular screening beginning at age 45 for average-risk adults, but other countries may use different ages and tests.
• Options include fecal immunochemical testing, high-sensitivity guaiac testing, stool DNA plus FIT, colonoscopy, flexible sigmoidoscopy, and CT colonography.
• An abnormal non-colonoscopy screening test generally requires diagnostic colonoscopy.
• People at high risk may need earlier and more frequent colonoscopy.
• Colonoscopy can detect cancer and remove some precancerous polyps.
• Risk reduction includes physical activity, healthy weight, not smoking, limiting alcohol, and a dietary pattern rich in vegetables, fruit, and whole grains.
• Aspirin may reduce risk for selected people but can cause serious bleeding and should not be promoted as a self-directed cancer-prevention strategy.

Diagnosis is discussed within the Overview, Screening, Staging, and Biomarkers sections above for this cancer type. Specific tests depend on presentation, site, and pathology.

TNM staging is combined into stages I through IV.

T describes how deeply the tumor has grown through the bowel wall or into nearby structures; N describes regional lymph nodes; M describes distant metastasis.

Histologic grade describes gland formation and cellular differentiation.

Rectal cancer evaluation also considers distance from the anal verge, mesorectal fascia, circumferential resection margin, and pelvic MRI findings.

A colon cancer and a rectal cancer at the same anatomic stage may still require different local treatment.

The classic adenoma-carcinoma pathway often involves APC, KRAS, and TP53. The serrated pathway is often associated with BRAF, CpG island methylation, and, in some tumors, mismatch-repair deficiency.

Mismatch-repair deficiency can cause high microsatellite instability. WNT, MAPK, PI3K, TGF-beta, angiogenesis, immune regulation, and the intestinal microenvironment influence tumor behavior. Microbiome research is active, but commercial microbiome testing should not be presented as a routine treatment-selection tool.

• MMR proteins and/or MSI: important for Lynch syndrome evaluation, prognosis, and immunotherapy selection
• KRAS and NRAS: important for determining whether anti-EGFR therapy may be appropriate
• BRAF V600E: prognostic and therapeutic relevance and useful context for some abnormal MMR results
• HER2 amplification or overexpression in a subset of metastatic disease
• KRAS G12C for selected targeted combinations
• NTRK fusions, which are rare but potentially actionable
• CEA for monitoring in selected patients, but not for population screening or diagnosis by itself
• Circulating tumor DNA as an emerging tool for postoperative molecular residual disease assessment

The clinical value of ctDNA is evolving. It should not be described as a universally established replacement for standard staging or surveillance.

• KRAS
  Kirsten Rat Sarcoma viral oncogene

• Early colon cancer: surgery removes the tumor and regional lymph nodes. Adjuvant chemotherapy may be discussed for selected stage II and many stage III cancers.
• Locally advanced rectal cancer: treatment may include chemoradiation or total neoadjuvant therapy before surgery.
• A nonoperative watch-and-wait strategy is being studied and used only in carefully selected complete responders with expert surveillance.
• Metastatic disease: systemic treatment is combined, when appropriate, with surgery, ablation, or radiation. Limited liver or lung metastases may be treated with curative intent in selected patients.
• MSI-high or mismatch-repair-deficient metastatic disease often receives immunotherapy.
• Treatment selection may incorporate RAS, BRAF, HER2, MSI/MMR, primary tumor location, symptoms, resectability, and organ function.

• Fluoropyrimidines and chemotherapy: 5-fluorouracil, leucovorin, capecitabine, oxaliplatin, and irinotecan
• Common regimen frameworks: FOLFOX, CAPOX, FOLFIRI, and FOLFOXIRI
• Anti-VEGF therapy: bevacizumab, aflibercept, or ramucirumab
• Anti-EGFR therapy: cetuximab or panitumumab in an appropriate molecular context
• BRAF V600E-directed treatment: encorafenib with cetuximab, with or without a fluoropyrimidine-based chemotherapy backbone depending on line and approval
• KRAS G12C-directed treatment: sotorasib or adagrasib with an anti-EGFR antibody in defined settings
• Immunotherapy for MSI-high/dMMR disease: pembrolizumab, nivolumab, and nivolumab plus ipilimumab
• Later-line therapy: trifluridine/tipiracil, regorafenib, or fruquintinib
• HER2-directed combinations for selected HER2-positive metastatic disease

• Oxaliplatin: peripheral neuropathy and cold-triggered symptoms
• Irinotecan: early or delayed diarrhea and bone marrow suppression
• Fluoropyrimidines: mucositis, diarrhea, hand-foot syndrome, and possible cardiac toxicity; severe toxicity can occur in people with DPD deficiency
• Anti-VEGF therapy: hypertension, bleeding, thrombosis, delayed wound healing, and rare gastrointestinal perforation
• Anti-EGFR therapy: acneiform rash, low magnesium, and infusion reactions
• Immunotherapy: immune-related colitis, hepatitis, endocrinopathies, and other inflammatory toxicities
• Supportive care may include ostomy education, diarrhea management, nutrition, anemia treatment, neuropathy monitoring, pain control, and psychosocial support.

Severe abdominal pain, persistent vomiting, inability to pass stool or gas, high fever, major bleeding, or dehydration needs urgent medical evaluation.

• Immunotherapy is being studied as a way to avoid radiation and surgery in selected dMMR/MSI-high locally advanced rectal cancers, but this approach requires expert multidisciplinary care and intensive follow-up.
• Circulating tumor DNA is being evaluated to guide adjuvant treatment intensity and recurrence monitoring.
• Targeted combinations are expanding for KRAS G12C, BRAF V600E, and HER2-positive disease.
• Rectal cancer research is refining total neoadjuvant therapy and organ-preservation strategies.
• Studies of early-onset colorectal cancer are examining biology, inherited risk, environmental exposure, and delays in diagnosis.
• Recent U.S. regulatory examples include approval of nivolumab plus ipilimumab for unresectable or metastatic MSI-high/dMMR colorectal cancer on April 8, 2025, and traditional approval of encorafenib with cetuximab and fluorouracil-based chemotherapy for BRAF V600E metastatic colorectal cancer on February 24, 2026.

• Is the tumor in the colon or rectum, and what is its exact location?
• What are the TNM stage, margins, and lymph-node findings?
• Have MMR/MSI, KRAS, NRAS, BRAF, and other necessary tests been completed?
• Should I have genetic counseling for Lynch syndrome or another inherited condition?
• Do I need treatment before surgery or after surgery?
• Is rectal preservation or avoidance of a permanent ostomy realistic in my case?
• If there are liver or lung metastases, can they be resected or ablated?
• How will neuropathy, diarrhea, and ostomy-related issues be prevented and managed?
• Does ctDNA have a clear, evidence-supported role in my care?
• Are there clinical trials relevant to my molecular subtype?