Colorectal Cancer for USMLE Step 2

Colorectal Cancer for the USMLE Step 2 Exam

Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer-related death in the United States.
It primarily affects adults over the age of 50, with increasing incidence in younger populations.
Screening programs have significantly reduced mortality by enabling earlier detection.

Age: Most cases occur in individuals over 50 years of age.
Dietary factors: Diets high in red meat, processed foods, and low in fiber are associated with increased risk.
Family history: First-degree relatives with CRC increase the risk, particularly if diagnosed at a younger age.
Hereditary syndromes:
Familial adenomatous polyposis (FAP): Caused by mutations in the APC gene, leading to hundreds of polyps and near 100% risk of CRC.
Lynch syndrome (HNPCC): A result of defective mismatch repair genes, leading to high lifetime risk of CRC and other cancers.
Inflammatory bowel disease: Chronic inflammation in ulcerative colitis or Crohn's disease predisposes to CRC.
Lifestyle factors: Obesity, smoking, alcohol consumption, and physical inactivity increase CRC risk.

CRC develops primarily from adenomatous polyps through the adenoma-carcinoma sequence, where mutations in genes like APC, KRAS, and TP53 promote malignant transformation.
Microsatellite instability (MSI) is an alternative pathway, particularly in patients with Lynch syndrome, involving defects in mismatch repair genes.

Right-sided colon cancer: Commonly presents with vague symptoms such as iron deficiency anemia, fatigue, and weight loss due to occult bleeding.
Left-sided colon cancer: Typically presents with more obvious symptoms, such as changes in bowel habits (e.g., constipation, diarrhea, or alternating patterns), hematochezia, and signs of bowel obstruction.
Rectal cancer: May cause rectal bleeding, tenesmus, and a sensation of incomplete evacuation.
Advanced disease: Systemic symptoms like weight loss, anorexia, and fatigue. The liver is the most common site of metastasis.

Colonoscopy is the gold standard for both CRC screening and diagnosis, recommended for average-risk individuals starting at age 45.
Other screening methods include:
Fecal immunochemical test (FIT): Annual test to detect occult blood in the stool.
Flexible sigmoidoscopy: Visualizes the distal colon, recommended every 5 years.
CT colonography: Every 5 years for those who cannot undergo colonoscopy.

Colonoscopy with biopsy confirms the diagnosis of CRC.
CT scan of the chest, abdomen, and pelvis is used to stage the disease and detect metastasis.
Carcinoembryonic antigen (CEA) is a tumor marker used for post-treatment surveillance, though it has limited value in the initial diagnosis.

The TNM system is used for staging:
T: Tumor depth and invasion.
N: Lymph node involvement.
M: Distant metastasis.
Early-stage CRC (stage I or II) has a much better prognosis than advanced or metastatic disease (stage IV).

Surgical resection is the treatment of choice for localized disease, with the extent of surgery (e.g., hemicolectomy, sigmoidectomy) depending on the tumor location.
Adjuvant chemotherapy is indicated for stage III disease or high-risk stage II disease.
For metastatic CRC, systemic chemotherapy (e.g., FOLFOX, FOLFIRI) is used, often combined with targeted therapies (e.g., bevacizumab for anti-VEGF or cetuximab for anti-EGFR in certain cases).

Prognosis depends on the stage at diagnosis:
Stage I: 5-year survival >90%.
Stage IV: 5-year survival <10%, but selected patients with limited metastases may benefit from aggressive treatment including metastasectomy.

Lifestyle changes such as a high-fiber diet, regular physical activity, and limiting red and processed meats reduce CRC risk.
Screening and removal of adenomatous polyps during colonoscopy are essential preventive measures.

Key Points

Colorectal cancer typically arises from adenomatous polyps through the adenoma-carcinoma sequence, driven by mutations in genes like APC, KRAS, and TP53.
Microsatellite instability is seen in Lynch syndrome and involves defective mismatch repair genes.
Colonoscopy is the gold standard for screening and diagnosis, with regular screening starting at age 45 for average-risk individuals.
Right-sided CRC presents with anemia and vague symptoms, while left-sided CRC typically presents with hematochezia and changes in bowel habits.
Surgical resection is the primary treatment for localized disease, while chemotherapy is used in advanced and metastatic cases.
Prevention includes lifestyle modifications and regular screening to detect and remove polyps before they become cancerous.