Intrathoracic core needle biopsy and repeat biopsy for PD-L1 evaluation in non-small cell lung cancer

Over the past years, the improved knowledge on the biological, genetic and molecular heterogeneity of tumors, together with the development of pharmaceutical technologies, has allowed the identification of several targets for novel therapeutic strategies. This fast process has led to the overall reconsideration of the biological peculiarities that can make each tumor a pathology on its own. Non-small cell lung cancer (NSCLC) has been object of extensive research, showing clearly different pathologic and biomolecular features, and an in-depth analysis of tumor genomes and signaling pathways may currently define a set of distinct diseases with specific genetic and cellular features (1). Until recently, genetic mutations or cytogenetic abnormalities (i.e., EGFR mutation, ALK translocation and many other targetable genetic lesions) have been the main drivers for a personalized therapeutic approach (2). As the therapeutic role of immune checkpoint inhibitors targeting programmed death-1 (PD-1 inhibitors, nivolumab, pembrolizumab) and programmed death ligand-1 (PD-L1 inhibitors, atezolizumab, durvalumab) rapidly raised popularity, by showing striking survival gains for NSCLC patients, both when used as single agents or in combination with chemotherapy or chemo-radiotherapy, in second line and first line, PD-L1 expression evaluation and re-evaluation on tissue samples became crucial both at diagnosis and after therapy (3). PD-L1 expression is currently assessed by immunohistochemistry (IHC), with a very wide range of positivity, ranging from 1% to 100% (4). While tumor molecular profiling for genetic alterations such as EGFR mutation or ALK translocation became part of the routine diagnostic workflow, we and others started reporting the feasibility and accuracy of tumor mutational screening in aspirated lung cancer cells [fine needle aspiration (FNA)] through imaging guidance (5-7). At the same time many other groups showed the feasibility and reliability of core needle biopsy (CNB) for lung cancer molecular profiling. FNA cytology was recently shown to be as accurate as CNB for PD-L1 testing in retrospective studies (8,9), but a recent study by Tsai and collaborators (10) shed new light on this topic, describing for the first time the feasibility and diagnostic accuracy of CT-guided transthoracic CNB for PD-L1 expression in a prospective series of 110 biopsies derived from the KEYNOTE-001 study population; 91.8% of these procedures were performed as repeat biopsies subsequent to a previous diagnostic procedure, as pembrolizumab was tested in second line, and