Colorectal Cancer Clinical Overview

Introduction

Colorectal cancer (CRC) encompasses malignancies of the colon and rectum and is one of the most common gastrointestinal cancers. Incidence rises after age 45–50. Rectal cancer historically accounts for a large proportion of CRC cases in many regions. Most CRCs are adenocarcinomas, with mucinous and signet‑ring variants carrying distinct prognostic implications.

Risk Factors and Etiology

• Diet and lifestyle: high red/processed meat intake, low dietary fiber, obesity, physical inactivity, alcohol use, and smoking.
• Medical conditions: inflammatory bowel disease (ulcerative colitis, Crohn colitis), type 2 diabetes.
• Polyps and precursor lesions: adenomatous and serrated polyps.
• Hereditary syndromes: Lynch syndrome (MMR gene variants), familial adenomatous polyposis (APC), MUTYH‑associated polyposis, and others.

Pathology and Patterns of Spread

• Histology: adenocarcinoma predominates; mucinous and signet‑ring variants may be chemo‑resistant and present at advanced stages.
• Gross morphologies: exophytic (polypoid/cauliflower), ulcerative, and infiltrative (“napkin‑ring”/stricture‑forming) patterns.
• Metastatic routes:
• Lymphatic spread to pericolic/perirectal nodes and along mesenteric vessels.
• Hematogenous spread to the liver via the portal system and to lungs via systemic circulation.
• Direct invasion into adjacent organs (e.g., bladder, uterus, stomach) and peritoneal seeding (especially mucinous tumors).

Clinical Presentation

• Altered bowel habits, iron‑deficiency anemia, rectal bleeding/melena, abdominal pain, weight loss.
• Right‑sided lesions: occult bleeding, anemia; left‑sided lesions: change in caliber, obstruction; rectal lesions: tenesmus, hematochezia.

Diagnosis

• Colonoscopy: gold standard for detection, biopsy, and polypectomy.
• Pathology: histologic confirmation; mismatch repair (MMR) IHC or MSI testing to screen for Lynch syndrome and prognostication.
• Staging: contrast‑enhanced CT chest/abdomen/pelvis; MRI pelvis for rectal cancer; CEA baseline.

Staging (AJCC TNM)

• T: depth of invasion through the bowel wall.
• N: number of regional lymph nodes involved.
• M: presence of distant metastasis (liver, lung, peritoneum, etc.).

Management

Colon Cancer

• Localized disease: oncologic colectomy with high ligation and adequate lymphadenectomy (≥12 nodes) is standard; adjuvant chemotherapy for stage III and selected high‑risk stage II.
• Obstruction/perforation: consider stenting (bridge to surgery) or urgent surgery; manage sepsis.

Rectal Cancer

• Local staging with MRI; multidisciplinary planning.
• Locally advanced (cT3/4 or N+): total neoadjuvant therapy (chemoradiation and systemic chemotherapy) followed by total mesorectal excision (TME); non‑operative “watch‑and‑wait” may be considered for complete clinical responders in qualified centers.
• Early T1 lesions: local excision if favorable features; otherwise TME.

Metastatic CRC

• Molecular profiling: RAS/RAF, HER2, MSI/dMMR to guide targeted therapy and immunotherapy.
• Systemic therapy backbones: fluoropyrimidine + oxaliplatin/irinotecan; biologics (anti‑VEGF, anti‑EGFR in RAS wild‑type left‑sided tumors); immunotherapy for MSI‑H/dMMR.
• Oligometastatic disease: consider metastasectomy or ablative therapy (liver, lung) within MDT.

Surveillance and Prevention

• Post‑treatment surveillance: periodic history/physical, CEA, CT imaging, and colonoscopy per guideline stage.
• Screening: average‑risk adults begin at age 45 with one of the following—colonoscopy (q10y), FIT (q1y), FIT‑DNA (q3y), CT colonography (q5y), or flexible sigmoidoscopy (q5–10y). Positive non‑colonoscopy tests should be followed by diagnostic colonoscopy.
• Risk reduction: maintain healthy weight, physical activity, limit alcohol, avoid smoking; consider aspirin chemoprevention for selected high‑risk individuals after risk–benefit discussion.

Key Takeaways

• Most CRCs arise from premalignant polyps; screening and polypectomy prevent cancer and reduce mortality.
• Management is stage‑ and site‑specific; rectal cancer requires MRI staging and MDT planning.
• Molecular profiling informs therapy in advanced disease and identifies hereditary syndromes.