Which laboratory tests should be obtained to evaluate an adult patient without known malignancy for possible cancer?

Blood Tests to Rule Out Cancer in Adults Without Known Malignancy

For adults without known malignancy being evaluated for possible cancer, obtain a basic laboratory panel including complete blood count with differential, comprehensive metabolic panel (electrolytes, liver function tests, calcium, LDH, albumin), and context-specific tumor markers based on clinical presentation—but recognize that blood tests alone cannot rule out cancer and must be interpreted alongside clinical findings and imaging. 1, 2

Core Laboratory Panel

The minimal basic workup should include:

• Complete blood count (CBC) with differential and peripheral blood smear review to identify cytopenias, abnormal cell counts, or circulating abnormal cells 2, 3
• Comprehensive metabolic panel including liver function tests (ALT, AST, alkaline phosphatase, bilirubin), serum calcium, creatinine, and albumin 1, 2
• Lactate dehydrogenase (LDH) as an independent adverse prognostic marker and general indicator of tissue breakdown 1, 2

These basic tests identify abnormalities that strongly suggest metastatic disease presence, though they don't necessarily localize the primary site. 1

Context-Specific Tumor Markers

Tumor marker selection must be guided by clinical presentation, not ordered indiscriminately:

For Males with Midline Masses or Nodal Disease

• α-fetoprotein (AFP) and β-human chorionic gonadotropin (β-hCG) to exclude potentially curable extragonadal germ cell tumors 1, 2
• Prostate-specific antigen (PSA) in males with adenocarcinoma or bone metastases to identify hormone-sensitive prostate cancer 1, 2

For Females with Specific Presentations

• Estrogen and progesterone receptors on tissue from females with axillary lymphadenopathy to rule out breast cancer 1
• CA-125 and CA15-3 for suspected gynecological or breast primaries 2
• CA-125 specifically for females with peritoneal carcinomatosis suggesting ovarian-type cancer 1

For Suspected Gastrointestinal Primary

• Carcinoembryonic antigen (CEA), CA19-9, and CA72-4 when gastrointestinal origin is suspected based on clinical or imaging findings 2

For Suspected Neuroendocrine Tumors

• Chromogranin A when neuroendocrine differentiation is suspected on pathology or clinical presentation 1, 2

Critical Interpretation Principles

Blood test abnormalities increase cancer probability but cannot definitively rule out malignancy. 4 Key considerations:

• Multiple abnormal blood tests increase cancer likelihood more than single abnormalities—patients with specific combinations of two abnormal tests have 23-62% probability of cancer 4
• Most blood test abnormalities are non-specific to cancer and can reflect inflammatory conditions, infections, or other benign processes 4
• Normal blood tests do not exclude cancer—they cannot be used as a stand-alone tool to rule out malignancy 4

High-Risk Clinical Scenarios Requiring Lower Threshold

Certain presentations warrant more aggressive evaluation even with normal or minimally abnormal labs:

• Clinical stage IIIA/IIIB lung cancer with mediastinal (N2) node involvement has higher rates of distant metastases even without clinical symptoms 1
• Males or females aged ≥60 with abdominal pain or bloating warrant consideration for urgent cancer referral regardless of blood test results (pre-test cancer risk >3%) 5
• Patients aged 30-59 with abdominal symptoms plus concurrent blood abnormalities (raised ferritin, low albumin, raised platelets, raised inflammatory markers, or anemia) have substantially elevated cancer risk requiring further investigation 5

Integration with Clinical Assessment

Blood tests must be interpreted within the context of:

• Thorough history and physical examination including assessment of performance status, weight loss, and organ-specific symptoms 1
• Clinical screening panel abnormalities (abnormal hemoglobin, electrolytes, liver function, calcium) that collectively suggest metastatic disease presence 1
• Imaging findings from CT of chest/abdomen/pelvis, which constitute the minimal radiographic workup 1

Common Pitfalls to Avoid

• Do not order comprehensive tumor marker panels indiscriminately—this leads to false positives and unnecessary workup 2
• Do not rely on blood tests alone to exclude cancer—tissue diagnosis remains the gold standard 6, 4
• Do not delay imaging or tissue biopsy while waiting for tumor marker results in patients with high clinical suspicion 1, 6
• Do not assume all elevated tumor markers indicate cancer—benign conditions frequently cause elevations 4, 7

When Tissue Diagnosis is Mandatory

Proceed directly to biopsy rather than relying on blood tests when:

• Imaging reveals suspicious masses or lymphadenopathy that would change management if malignant 6
• Clinical presentation strongly suggests malignancy (unexplained weight loss, progressive symptoms, high-risk age group) 1, 6
• Blood test abnormalities are present but non-specific 4

Tissue provides definitive diagnosis, histologic subtype, and material for immunohistochemistry and molecular testing that guide treatment decisions. 1, 6