What laboratory tests are used in the diagnosis and management of colon cancer?

Laboratory Tests for Colon Cancer Diagnosis and Management

The essential laboratory tests for colon cancer include complete blood count, comprehensive metabolic panel with liver and kidney function tests, albumin, coagulation studies, and carcinoembryonic antigen (CEA) levels, which must be obtained before initiating definitive treatment. 1

Initial Diagnostic Laboratory Workup

Standard Blood Tests

• Complete blood count (CBC) to assess for anemia from chronic blood loss, which is a common presenting feature of colon cancer 1
• Comprehensive metabolic panel including liver function tests (transaminases, alkaline phosphatase, bilirubin) and kidney function tests (creatinine, BUN) to evaluate baseline organ function and detect potential metastatic disease 1
• Albumin levels to assess nutritional status and overall patient condition before treatment decisions 1
• Coagulation studies to evaluate bleeding risk prior to surgical intervention 1

Tumor Marker Testing

Carcinoembryonic antigen (CEA) must be measured preoperatively despite its low sensitivity and specificity for diagnosis, as it provides critical prognostic information and serves as a baseline for postoperative surveillance. 1

• CEA levels >5 ng/ml (or even >2.35 ng/ml) indicate worse prognosis 1
• An elevated preoperative CEA that fails to normalize within 1 month after surgical resection suggests persistent disease 1
• CEA is insufficient for diagnosis alone and requires confirmatory tissue biopsy due to low sensitivity and specificity 1
• The primary value of CEA is in postoperative monitoring for early detection of metastatic disease recurrence 1

Molecular Biomarker Testing

Tissue-Based Molecular Testing

All metastatic or recurrent colorectal carcinoma tissues must undergo molecular biomarker testing using validated methods with sufficient performance characteristics, with metastatic tissue preferred over primary tumor when available. 1

Required Molecular Tests:

• RAS mutation testing (KRAS and NRAS) to predict response to anti-EGFR therapy in metastatic disease 1
• BRAF mutation testing for prognostic stratification 1
• Microsatellite instability (MSI) testing or mismatch repair (MMR) protein immunohistochemistry (MLH1, MSH2, MSH6, PMS2) for all colorectal cancers to identify Lynch syndrome and predict response to immunotherapy 1

Specimen Requirements:

• Formalin-fixed paraffin-embedded (FFPE) tissue is the acceptable standard specimen for molecular testing 1
• Laboratories must validate tumor cell content and establish minimum thresholds based on assay performance characteristics 1
• At least 12 lymph nodes must be examined for adequate pathological staging 1, 2

Validation Standards

Laboratories must validate all molecular biomarker testing methods according to best laboratory practices, with clinical validation assessing analytical sensitivity, analytical specificity, clinical sensitivity, and clinical specificity. 1

• Multiplexed assays should be used to optimize tissue utilization, particularly in small specimens 1
• Testing turnaround time should meet clinical needs, with 90% of send-out specimens processed within 3 working days 1
• False-positive RAS results lead to inappropriate withholding of therapy, while false-negative results cause ineffective treatment with unnecessary toxicity and costs 1

Surveillance Laboratory Testing

Postoperative Follow-Up Schedule

CEA levels should be checked every 3-6 months for the first 3 years, then every 6-12 months for years 4-5 after surgery if initially elevated. 1, 3

• High-risk patients (stage III) require CEA monitoring every 3 months for the first 3 years 3
• Moderate-risk patients (stage II) require CEA monitoring every 3-6 months for the first 3 years 3
• Rising CEA levels during surveillance indicate possible recurrence requiring further imaging evaluation 3, 4

Additional Surveillance Tests

• Complete blood count and liver function tests should be obtained at each surveillance visit 1, 3
• Routine laboratory tests beyond CEA have unproven benefit and should be restricted to symptomatic patients 1

Critical Pitfalls to Avoid

• Never rely on CEA alone for diagnosis without tissue confirmation, as sensitivity and specificity are too low for diagnostic purposes 1
• Never proceed with anti-EGFR therapy without RAS mutation testing, as RAS mutations predict lack of response and unnecessary toxicity 1
• Never accept inadequate lymph node sampling (<12 nodes examined), as this leads to inaccurate staging and suboptimal treatment decisions 1, 2
• Never use unvalidated molecular testing methods, as improper validation leads to erroneous results affecting diagnosis, prognosis, and therapeutic intervention 1
• Never delay molecular biomarker testing in metastatic disease, as results directly impact treatment selection and should be initiated in a timely fashion 1

Emerging Laboratory Tests

While fecal immunochemical tests (FIT), stool DNA tests, and liquid biopsy assays show promise for screening and monitoring, these methods currently await robust validation for routine clinical use beyond screening programs 1, 5. Liquid biopsy for circulating tumor DNA may eventually play a role in monitoring recurrence and treatment resistance, but clinical utility requires further validation 1.