When should a biopsy be obtained to rule out small cell transformation in a patient with stage IV NSCLC and an EGFR mutation?

Histologic transformation is a well-described but poorly understood - and under-diagnosed - mechanism of resistance to TKIs. The best known is small cell transformation in EGFR mutant NSCLC but transformation, to either small cell or squamous cell, has been seen with multiple different TKIs.

Biopsy ...