What are the diagnostic tests for lung cancer?

Diagnostic Testing for Lung Cancer

For patients with suspected lung cancer, obtain tissue diagnosis using the least invasive method appropriate to the clinical scenario: bronchoscopy for central lesions, transthoracic needle aspiration (TTNA) or bronchoscopy with radial probe ultrasound/electromagnetic navigation for peripheral lesions, and thoracentesis if pleural effusion is present. 1

Initial Imaging

• CT chest with contrast is the foundational imaging study for all patients with known or suspected lung cancer 2
• Extend CT to include liver and adrenal glands if PET scan is unavailable 2
• Chest X-ray and sputum cytology are not recommended for screening or diagnosis due to insufficient sensitivity 1

Tissue Acquisition Strategy Based on Tumor Location

Central Lesions

• Bronchoscopy is the primary diagnostic method for centrally located tumors 1
• Obtain samples via endobronchial biopsy, brushings, and washings 1
• If bronchoscopy is non-diagnostic but suspicion remains high, proceed to alternative methods 1

Peripheral Lesions

• Radial probe endobronchial ultrasound or electromagnetic navigation bronchoscopy if equipment and expertise available 1
• TTNA is the alternative when advanced bronchoscopic techniques are unavailable or unsuccessful 1
• For peripheral nodules <2 cm, transparietal needle biopsy is preferred 1

Mediastinal Involvement

• EBUS-guided needle aspiration (EBUS-NA) or EUS-guided needle aspiration (EUS-NA) for accessible mediastinal lymph nodes 1, 2
• These minimally invasive techniques should be attempted before mediastinoscopy 1
• Mediastinoscopy reserved for cases where EBUS/EUS is non-diagnostic 1

Pleural Effusion Present

• Ultrasound-guided thoracentesis is the first step to diagnose the cause of pleural effusion 1, 2
• Ultrasound guidance improves success rate and decreases pneumothorax risk 1
• If initial pleural fluid cytology is negative, consider second thoracentesis (increases diagnostic yield) or proceed directly to pleural biopsy via image-guided biopsy, medical thoracoscopy, or surgical thoracoscopy 1
• If CT shows pleural thickening or nodules/masses, image-guided needle biopsy may be considered as first step 1

Metastatic Disease Suspected

• If solitary extrathoracic metastasis suspected, obtain tissue confirmation from the metastatic site if FNA or biopsy is feasible 1
• If multiple distant metastases present but biopsy would be technically difficult, diagnose the primary lung lesion by least invasive method 1

Tissue Adequacy Requirements

• Obtain sufficient tissue for both histologic typing AND molecular analysis (EGFR, ALK, ROS1, BRAF, PD-L1) 1, 2
• Cytology specimens from EBUS-TBNA, pleural fluid, and other sources can detect EGFR and K-ras mutations in 72-79% of cases 3
• If initial specimen is inadequate, repeat biopsy is necessary 2
• Effective communication between proceduralists, pathologists, and oncologists is critical to optimize tissue use 1

Role of Liquid Biopsy

• Liquid biopsy (ctDNA) is complementary to—not a replacement for—tissue biopsy 3
• FDA-approved only for EGFR mutation detection in circulating tumor DNA 3
• Use liquid biopsy when: tissue biopsy unsuccessful or insufficient, patient unable to tolerate invasive procedures, or need for serial monitoring during treatment 3
• Tissue biopsy remains the gold standard for diagnosis 3

Sputum Cytology

• Sputum cytology is not specific for lung cancer and histological confirmation must be obtained 1
• If sputum cytology is negative, further testing is required 1
• Sensitivity varies by tumor location and sputum processing methods 1

Screening Context (Asymptomatic High-Risk Patients)

• Low-dose CT (LDCT) screening reduces lung cancer mortality by 20-24% in high-risk populations 1, 4, 5
• Recommended for current or former heavy smokers (≥30 pack-years, ≤15 years since cessation) aged 55-74 years 1
• Chest X-ray screening is not recommended (Grade 1A) 1
• Sputum cytology screening is not suggested (Grade 2B) 1
• LDCT screening should only be performed within dedicated programs with quality control and multidisciplinary management 1

Tests NOT Recommended

• CEA and other serum tumor markers should not be used for screening, diagnosis, staging, or surveillance 6
• Routine hematological and biochemical tests do not replace history and clinical examination 1

Critical Pitfalls to Avoid

• Never accept cytology diagnosis alone without adequate tissue for molecular characterization when feasible 1
• Do not stop after negative TBNA—negative predictive value is insufficient; proceed to mediastinoscopy if clinical suspicion remains high 2
• Do not rely on chest X-ray or sputum cytology as primary diagnostic tools in symptomatic patients 1
• Avoid false reassurance from negative liquid biopsy—tissue confirmation remains essential 3