What are the recommended screening, staging, and treatment strategies for colon cancer in adults aged 45 and older or with risk factors such as family history, inflammatory bowel disease, hereditary syndromes (e.g., Lynch syndrome, familial adenomatous polyposis), or prior adenomatous polyps?

Colon Cancer: Screening, Staging, and Treatment

Screening Recommendations

Average-Risk Adults

Begin colorectal cancer screening at age 45 years for all average-risk adults, using colonoscopy every 10 years or annual fecal immunochemical testing (FIT) as first-tier options. 1

• Colonoscopy every 10 years is the preferred screening modality because it detects and removes precancerous polyps in the same procedure, directly preventing cancer with the highest sensitivity for advanced adenomas. 1
• Annual FIT reduces colorectal cancer mortality by approximately 15% in randomized trials and has 95% specificity, but requires strict annual adherence and follow-up colonoscopy for any positive result. 2, 1
• Continue screening through age 75 years with high-certainty mortality benefit. 1
• Individualize screening for ages 76-85 years based on prior screening history, life expectancy ≥10 years, and overall health status. 1
• Discontinue screening after age 85 years as harms outweigh benefits. 1

Alternative Screening Options (when first-tier tests declined)

• Flexible sigmoidoscopy every 5-10 years reduces CRC incidence and mortality, with optimal age range 55-64 years; combine with annual FOBT to reduce right colon cancer risk. 2
• Multitarget stool DNA (FIT-DNA/Cologuard) every 3 years is acceptable but has lower specificity (87%) resulting in more false positives. 1
• CT colonography every 5 years requires bowel preparation without sedation, but abnormal findings mandate colonoscopy. 1

Tests NOT Recommended

Blood-based screening assays (e.g., Shield, SEPT9) are not recommended because no mortality benefit has been demonstrated. 1

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High-Risk Populations Requiring Enhanced Surveillance

Family History

Individuals with one first-degree relative diagnosed with colorectal cancer before age 60, or two or more first-degree relatives at any age, should begin colonoscopy at age 40 or 10 years before the youngest affected relative (whichever is earlier), repeated every 5 years. 2, 1

• Patients with a first-degree relative diagnosed with CRC have a relative risk 1.72-3.26 times higher, increasing to 3.57 if diagnosed before age 50. 3
• Verify family history information directly as it is often incomplete or inaccurate; confirm diagnosis and age of onset in affected relatives. 3

Personal History of Adenomatous Polyps

Surveillance colonoscopy intervals depend on polyp characteristics: 2

• Low-risk adenomas (1-2 tubular adenomas <1 cm): repeat colonoscopy in 5 years. 2
• Advanced adenomas (≥1 cm, high-grade dysplasia, or ≥25% villous features): repeat colonoscopy in 3 years. 2
• 3-10 adenomatous polyps: repeat colonoscopy in 3 years. 2
• >10 cumulative adenomas: consider polyposis syndrome evaluation. 2
• Incomplete/piecemeal polypectomy of large sessile polyps: repeat colonoscopy in 2-6 months. 2

Personal History of Colorectal Cancer

Colonoscopy at 1 year post-resection; if normal, repeat in 3 years, then every 5 years if still normal. 2

Inflammatory Bowel Disease

Patients with ulcerative colitis or Crohn's disease affecting the colon require surveillance colonoscopy beginning 8 years after symptom onset, repeated every 1-2 years. 2

• Risk greatly increases 8 years after pancolitis onset or 12-15 years after left-sided colitis onset. 2

Hereditary Syndromes

All patients with suspected hereditary syndromes require genetic counseling and syndrome-specific surveillance: 2

Lynch Syndrome (Hereditary Non-Polyposis Colorectal Cancer)

• Begin colonoscopy at age 20-25 years (or 2-5 years before youngest family diagnosis), repeated every 1-2 years. 2, 4
• Carriers have 30-80% cumulative lifetime risk of CRC with mean diagnosis age 45 years. 3
• 30% present with synchronous or metachronous cancers. 3

Familial Adenomatous Polyposis (FAP)

• Begin surveillance endoscopy at puberty (age 10-12 years), repeated every 1-2 years. 2, 4
• Consider prophylactic colectomy if genetic testing confirms mutation; otherwise continue annual endoscopy. 2
• Accounts for 1% of all colorectal cancers. 2

MUTYH-Associated Polyposis (MAP)

• Requires genetic counseling and intensified surveillance similar to attenuated FAP. 2

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Staging

Preoperative Staging

Complete preoperative staging includes: 2

• Clinical examination
• Complete blood count, liver and renal function tests
• Carcinoembryonic antigen (CEA) level
• Chest X-ray or CT scan
• CT scan of abdomen and pelvis
• Complete colonoscopy of entire large bowel; if obstructing lesion prevents complete exam, repeat colonoscopy 3-6 months postoperatively. 2
• Intraoperative ultrasound (IOUS) for suspected metastatic disease. 2

Pathologic Staging

Use TNM 2002/AJCC staging system with assessment of: 2

• Tumor depth (T stage): Tis, T1, T2, T3, T4
• Lymph node involvement (N stage): N0, N1, N2
• Distant metastases (M stage): M0, M1
• Adequate lymph node assessment: ≥12 regional lymph nodes must be examined for accurate staging. 2
• Resection margin status: R0 (complete, negative margins), R1 (microscopic involvement), R2 (gross residual). 2

High-Risk Features in Stage II Disease

High-risk factors indicating consideration for adjuvant chemotherapy in node-negative disease include: 2

• T4 tumor
• Poorly differentiated adenocarcinoma/undifferentiated carcinoma
• Vascular invasion
• Lymphatic vessel invasion
• Perineural invasion
• Obstruction or perforation at presentation
• <12 lymph nodes examined
• Elevated CEA level

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Treatment Strategies

Stage I (T1-2, N0, M0)

Surgical resection alone with no adjuvant chemotherapy. 2

• En bloc removal of tumor with adequate margins and regional lymph nodes. 2
• Laparoscopic resection by adequately trained surgeons is preferred when available. 5

Stage II (T3-4, N0, M0)

Surgical resection is primary treatment; adjuvant chemotherapy is considered only for high-risk features. 2

• Standard approach: Observation after complete resection for low-risk stage II. 2
• High-risk stage II: Consider fluoropyrimidine-based adjuvant chemotherapy (5-FU/leucovorin or capecitabine). 2
• T4 tumors or localized perforation/positive margins: Consider radiotherapy (category 2B). 2

Stage III (Any T, N1-2, M0)

Adjuvant chemotherapy is recommended for all stage III colon cancer. 2

• Standard regimen: FOLFOX (5-FU/leucovorin plus oxaliplatin) significantly improves disease-free survival and overall survival compared to 5-FU/leucovorin alone. 2
• Alternative options:
  • Infusional 5-FU/leucovorin regimens. 2
  • Capecitabine (at least as effective and less toxic than bolus 5-FU/LV). 2

Stage IV (Any T, Any N, M1)

Treatment depends on resectability of metastases: 2

• Resectable metastases: Colectomy with en bloc lymph node removal, synchronous or staged liver resection, followed by adjuvant chemotherapy (FOLFOX or FOLFIRI). 2
• Unresectable metastases: Systemic chemotherapy with consideration for palliative surgery if obstruction/perforation. 2
• Checkpoint inhibitors show dramatic response in dMMR/MSI-H metastatic CRC. 6

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Post-Treatment Surveillance

Surveillance aims to detect recurrence amenable to salvage surgery and identify metachronous cancers: 2

• History and physical examination: Every 3 months for 2 years, then every 6 months through year 5. 2
• CEA: Every 3 months for 2 years, then every 6 months through year 5 (for T2 or greater lesions). 2
• Colonoscopy: At 1 year post-resection; if normal, repeat every 3-5 years. If preoperative colonoscopy incomplete due to obstruction, perform at 3-6 months. 2
• Chest/abdominal/pelvic CT: Every 3-6 months for stage IV patients rendered disease-free (category 2B). 2
• Liver ultrasound: Every 6 months for 3 years may be considered. 2

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Critical Clinical Pitfalls

Do not rely solely on fecal occult blood tests to exclude neoplasia in high-risk patients (sensitivity 13-100% for cancer, 5-69% for polyps); proceed directly to colonoscopy. 3

Any positive stool-based test must be followed by diagnostic colonoscopy; failure to complete this step nullifies screening benefit. 1

Symptomatic patients (rectal bleeding, unexplained weight loss, change in bowel habits) require immediate diagnostic colonoscopy, not screening tests. 1

Colonoscopy may be less effective in the right colon than other segments; ensure complete examination with adequate bowel preparation. 2

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Primary Prevention

Modifiable lifestyle factors account for 50-58% of colorectal cancer cases: 1

• Reduce red and processed meat consumption. 1
• Limit alcohol intake. 1
• Increase fruits, vegetables, dietary fiber, and calcium. 1
• Maintain regular physical activity and healthy body weight. 1
• Avoid tobacco. 1
• Consider low-dose aspirin in selected individuals (balance bleeding risk). 1

Combining screening starting at age 45 with lifestyle modification can prevent up to 61% of colorectal cancer cases, compared to 32% with screening alone. 1