According to NCCN guidelines, should the primary lung mass be biopsied before the adrenal metastasis in a patient with an easily accessible FDG‑avid right lung tumor and adrenal nodule?

Should You Biopsy the Metastatic Site First? NCCN Guidance

Yes, NCCN guidelines explicitly recommend preferentially biopsying the metastatic site (adrenal nodule) first in this scenario, as it simultaneously establishes both diagnosis and the highest stage (Stage IV disease) in a single procedure. 1

Core NCCN Principle: Biopsy the Highest Stage First

The NCCN guidelines state a fundamental principle: "preferentially biopsy the abnormality that would simultaneously confer the highest tumor stage." 1 This approach maximizes diagnostic efficiency by:

• Establishing malignancy diagnosis
• Confirming metastatic disease (Stage IV)
• Avoiding unnecessary invasive procedures on the primary tumor
• Guiding treatment decisions immediately toward systemic therapy rather than surgical resection

Specific NCCN Recommendations for Your Scenario

For patients suspected of having metastatic disease, NCCN recommends confirmation from one of the metastatic sites if feasible. 1 The guidelines provide clear direction:

• Patients suspected of having a solitary site of metastatic disease should preferably have tissue confirmation of that site if feasible 1
• The finding of an isolated adrenal mass on imaging requires biopsy to rule out metastatic disease if the patient is otherwise considered potentially resectable 1, 2

When to Biopsy the Primary Instead

NCCN only recommends biopsying the primary lung lesion or mediastinal lymph nodes when: "it is technically difficult or very risky to biopsy a metastatic site" in patients who may have multiple sites of metastatic disease. 1

In your case with an easily accessible adrenal nodule, this exception does not apply.

Clinical Rationale

This approach is strategically sound because:

• If the adrenal biopsy confirms metastasis, you've established Stage IV disease and can proceed directly to systemic therapy without needing primary tumor biopsy 1
• If the adrenal biopsy shows benign adenoma (which occurs in many solitary adrenal masses even with lung cancer), you can then proceed to biopsy the primary tumor and potentially pursue curative surgical resection 1
• Biopsying the primary first wastes time and resources if the adrenal lesion turns out to be metastatic, as surgery would no longer be appropriate 1

Important Caveats

Ensure adequate tissue acquisition for molecular testing. Communication among the pathologist, medical oncologist, and practitioner performing the biopsy is essential to obtain sufficient tissue for EGFR mutation testing, ALK rearrangement testing, and other molecular markers that guide systemic therapy selection. 1, 2

The least invasive biopsy technique with the highest diagnostic yield should be selected for the adrenal lesion, typically CT-guided percutaneous needle biopsy. 1