What laboratory tests can be used to diagnose cancer in a patient?

Laboratory Tests for Cancer Diagnosis

No single laboratory test can definitively diagnose cancer—tissue biopsy remains the gold standard for diagnosis—but specific tumor markers and blood tests can guide the diagnostic workup and identify patients who need further investigation. 1

Essential Laboratory Workup for Suspected Cancer

When cancer is suspected, the initial laboratory evaluation should include:

Basic Laboratory Panel

• Complete blood count (CBC) to assess for anemia from chronic blood loss, leukemia, or bone marrow involvement 1, 2
• Comprehensive metabolic panel including liver function tests (ALT, AST, alkaline phosphatase, bilirubin), kidney function (creatinine), serum calcium, and lactate dehydrogenase (LDH) 1, 3
• Serum albumin to evaluate nutritional status and overall patient condition 4

These basic tests help identify organ dysfunction, metabolic abnormalities, and paraneoplastic syndromes that may suggest underlying malignancy 3.

Context-Specific Tumor Markers

Tumor marker selection depends entirely on clinical presentation and suspected primary site. Never use tumor markers alone for diagnosis—they lack sufficient sensitivity and specificity and must be combined with imaging and tissue confirmation. 4

For Males with Suspected Germ Cell Tumors

• Alpha-fetoprotein (AFP) and beta-human chorionic gonadotropin (β-hCG) are mandatory 3, 1
• These markers identify potentially curable extragonadal germ cell tumors 3

For Males with Possible Prostate Cancer

• Prostate-specific antigen (PSA) to identify hormone-sensitive tumors amenable to specific therapy 3, 1

For Females with Suspected Gynecological Primary

• Cancer antigen 15-3 (CA15-3) for breast cancer 1
• Cancer antigen 125 (CA125) for ovarian cancer 1
• Estrogen and progesterone receptors on tissue specimens for axillary node metastases 3

For Suspected Gastrointestinal Primary

• Carcinoembryonic antigen (CEA) for colorectal cancer—preoperative levels >5 ng/mL indicate worse prognosis 3, 1, 4
• Carbohydrate antigen 19-9 (CA19-9) for pancreatic and biliary cancers 3, 1
• Cancer antigen 72-4 (CA72-4) for gastric cancer 1

These markers can determine disease course and monitor treatment response despite non-specific elevations 1.

For Suspected Neuroendocrine Malignancy

• Chromogranin A and plasma chromogranin A to identify neuroendocrine tumors 3, 1

Specialized Testing for Hematologic Malignancies

Peripheral Blood Smear

• Manual peripheral blood smear examination as part of CBC with differential to check for malignant cells in suspected hematologic malignancy 2
• Critical caveat: A peripheral blood smear alone is insufficient for definitive diagnosis—bone marrow examination remains the gold standard for suspected leukemia 2

Follow-up Testing When Malignant Cells Are Suspected

• Bone marrow examination is typically the next step for definitive diagnosis 2
• Flow cytometry immunophenotyping on peripheral blood if sufficient abnormal cells are present 2
• Cytogenetic studies including FISH and/or conventional karyotyping 2
• Molecular studies for specific genetic abnormalities 2

Molecular Biomarker Testing (For Confirmed Cancer)

Once cancer is diagnosed by tissue biopsy, molecular testing guides treatment decisions:

For Metastatic Colorectal Cancer

• RAS mutation testing (KRAS and NRAS) is mandatory before anti-EGFR therapy—RAS mutations predict lack of response 3, 4
• BRAF mutation status for prognostic assessment and treatment with cetuximab-encorafenib 3, 4
• Microsatellite instability (MSI) testing or mismatch repair (MMR) protein immunohistochemistry to identify Lynch syndrome and predict response to immunotherapy 3, 4
• HER2 amplification by IHC or FISH in RAS-wild-type patients 3

For Cancer of Unknown Primary

• Immunohistochemistry panel including cytokeratins CK7 and CK20, TTF1, CDX2, GATA3, SOX10, synaptophysin, and chromogranin A to identify tissue of origin 3
• Testing must be carried out on good quality tissue specimens with adequate tumor cell content (>20%) 3

Critical Pitfalls to Avoid

• Never rely on CEA or any tumor marker alone for diagnosis without tissue confirmation—sensitivity and specificity are too low for diagnostic purposes 4
• Never proceed with anti-EGFR therapy without RAS mutation testing—RAS mutations predict lack of response and unnecessary toxicity 4
• Never use unvalidated molecular testing methods—improper validation leads to erroneous results affecting diagnosis, prognosis, and therapeutic intervention 4
• Never assume a negative tumor marker excludes cancer—many cancers do not produce elevated tumor markers 1
• Never order PET scans routinely for renal cell carcinoma—18FDG-PET is not a standard investigation and should not be used 3

Surveillance After Cancer Diagnosis

For patients with confirmed colorectal cancer after surgical resection:

• CEA levels every 3-6 months for the first 3 years, then every 6-12 months for years 4-5 if initially elevated 3, 4
• Rising CEA during surveillance indicates possible recurrence requiring further imaging 4
• Complete blood count and liver function tests at each surveillance visit 4