Can liquid biopsy be substituted for tissue biopsy in a lung mass that is radiologically suspicious for primary lung cancer when CT-guided biopsy cannot be done?

Generally, the utility of liquid biopsy remains in the ability to provide genomic information from cfDNA. A liquid biopsy will not provide a definitive tissue diagnosis and does not provide information about histology. When a histologic diagnosis is made with biopsy or FNA but the sample is insufficient for additional genomic testing, liquid biopsy can be helpful to define the molecular subtype.
In the specific example provided, a liquid biopsy would not replace a diagnostic tissue biopsy. Treatment would potentially differ in the setting of SCLC versus NSCLC. Even liquid biopsy may be negative if insufficient cfDNA is circulating and only tissue would confirm the molecular subtype in that setting.

I would accept the presence of a targetable mutation but I would still prefer to see histology to make a sound treatment decision. There are occasional cases of mixed histology and treatment choice can change based on that.