Colorectal Cancer

Detailed Overview

CRC is a major cause of cancer morbidity and mortality worldwide. It develops slowly, taking 10-15 years for a benign adenomatous polyp to undergo malignant transformation via acquired genetic mutations (APC, KRAS, TP53). Early stages are often asymptomatic, making screening colonoscopy starting at age 45 crucial. Right-sided lesions cause occult bleeding and anemia, while left-sided lesions cause obstruction and changes in bowel habits.

Epidemiology & Demographics

Third most common cancer and second leading cause of cancer death globally. Incidence is rising in adults under 50. Lifetime risk is roughly 4-5%.

Etiological Mechanism

Sporadic genetic mutations (80%), familial syndromes like Lynch syndrome or FAP (5-10%), or inflammatory bowel disease.

Primary Causes

Sequential accumulation of somatic mutations in the mucosal epithelium.

• Dietary Factors: High intake of red or processed meats and low intake of fiber.
• Family History: One first-degree relative with CRC doubles the risk.
• Inflammatory Bowel Disease: Long-standing ulcerative colitis or Crohn colitis significantly increases risk.

Chromosomal Instability Pathway (85%): Loss of the APC tumor suppressor gene leads to early adenoma. Subsequent mutation of the KRAS oncogene promotes late adenoma formation. Finally, loss of TP53 leads to frank adenocarcinoma. Microsatellite Instability Pathway (15%): Defective DNA mismatch repair genes (MLH1, MSH2) result in rapid accumulation of mutations, classic in Lynch Syndrome.

Characteristic Clinical Presentation

• Change in Bowel Habits: New-onset constipation, diarrhea, or pencil-thin stools (mostly left-sided tumors).
• Hematochezia: Bright red blood per rectum or melena.
• Unexplained Weight Loss: Systemic symptom of advanced malignancy.

Physical Examination Signs

• Palpable Abdominal Mass
• Positive Fecal Occult Blood
• Hepatomegaly

• Large Bowel Obstruction: Tumor fully occludes the lumen, causing severe distension and risk of cecal perforation.
• Tumor Bleeding: Chronic bleeding leading to severe iron-deficiency anemia and heart failure.

Diagnostic Criteria & Guidelines

Direct visualization via colonoscopy with biopsy confirming adenocarcinoma.

Differential Diagnosis

• Diverticulitis / Diverticular Bleed
• Inflammatory Bowel Disease
• Hemorrhoids (often falsely blamed for rectal bleeding in CRC)

Laboratory Tests & Biomarkers

• Carcinoembryonic Antigen (CEA): Elevated (>5 ng/mL). Used for monitoring recurrence, NOT for primary screening.
• CBC: Microcytic, hypochromic anemia (low Hb, low MCV) secondary to chronic occult blood loss.
• Mismatch Repair (MMR) Testing: Biopsy shows absent MLH1/MSH2 proteins if Lynch syndrome is present.

Imaging Modalities & Findings

• Colonoscopy:
• CT Chest/Abdomen/Pelvis:

• Stage I
  Tumor invades submucosa or muscularis propria (T1/T2). No nodes. 91% 5-year survival.
• Stage III
  Positive regional lymph nodes (N1/N2). ~72% 5-year survival.
• Stage IV
  Distant metastasis (M1) to liver or lungs. 14% 5-year survival.

Second-Line & Adjunctive Therapy

Adjuvant chemotherapy (FOLFOX: 5-FU, Leucovorin, Oxaliplatin) for 3-6 months for Stage III (node-positive) colon cancer. Biologics (Bevacizumab targeting VEGF, or Cetuximab targeting EGFR if KRAS wild-type) for metastatic Stage IV disease.

Surgical & Procedural Management

Low Anterior Resection (LAR) for upper/mid rectal tumors. Abdominoperineal Resection (APR) with permanent colostomy for low rectal tumors invading the sphincter.

Recommended Lifestyle Changes

• High fiber diet (fruits, vegetables, whole grains).
• Regular physical activity and weight management.

Patient Counseling & Advice

Ensure all first-degree relatives are informed, as they need early screening colonoscopy (10 years prior to the age of diagnosis of the patient).

Follow-Up & Monitoring Schedule

CEA testing every 3-6 months for 2 years. Colonoscopy at 1 year post-op, then 3 years, then every 5 years. Annual CT Chest/Abd/Pelvis for up to 5 years to monitor for hepatic/pulmonary mets.

Preventive Strategies

Screening via colonoscopy every 10 years starting at age 45 (or FIT test annually). Polypectomy removes the precursor lesion, directly preventing cancer.

Highly dependent on stage at diagnosis. Overall 5-year survival is 65%, but drops to 14% if metastatic.