Integrating endobronchial ultrasound bronchoscopy with molecular testing of immunotherapy biomarkers in non-small cell lung cancer

Abstract

Immunotherapy has transformed treatment of advanced non-small-cell lung cancer (NSCLC) patients leading to remarkable long-term survival benefit. However, only about 20% of advanced NSCLC patients typically respond to immune checkpoint inhibitors (ICIs) that target the PD-1/PD-L1 pathway.The only validated biomarker for ICI therapy is the PD-L1 immunohistochemistry (IHC) test, which is considered an imperfect assay due to several variables including availability and integrity of tumour tissue, variability in staining/scoring techniques and heterogeneity in PD-L1 protein expression within and across tumour biopsies. Herein, we discuss integrating minimally invasive EBUS bronchoscopy procedures with novel molecular approaches to improve accuracy and sensitivity of PD-L1 testing. EBUS guided bronchoscopy facilitates repeated sampling of tumour tissue to increase the probability of detecting PD-L1 positive tumours. Since intra-tumoural PD-L1 (CD274) copy number is reported to be less heterogeneous than PD-L1 protein detection, quantifying PD-L1 transcript levels may increase detection of PD-L1 positive tumours. PD-L1 transcript levels show excellent concordance with PD-L1 IHC scoring and multiplex digital droplet PCR (ddPCR) assays that quantify absolute PD-L1 transcript copy number have been developed. ddPCR can also be automated for high throughput detection of low abundant variants with excellent sensitivity and accuracy to improve the broader application of diagnostic cut-off values. Optimizing diagnostic workflows that integrate optimal EBUS bronchoscopy procedures with emerging molecular ICI biomarker assays may improve the selection criteria for ICI therapy benefit.

In EBUS Signo Vinces: New Indications in Thoracic Oncology for Mediastinal Lymph Node Staging Using Endobronchial Ultrasound

“…Radial probe EBUS is used to sample pulmonary parenchymal lesions, a unique technique that incorporates both cytologic and histologic sampling. Additionally, EBUS-TBNA sampling has been used to characterise the immunophenotypic properties of tumourdraining lymph nodes in not-small cell lung cancer (14).…”

Methods for assessment of the tumour microenvironment and immune interactions in non-small cell lung cancer. A narrative review

“…This method enables amplification of the signal for the detection of the target protein with light microscopy ( 28 ). Additionally, IHC can be performed effectively on small tissue samples such as those obtained via EBUS ( 29 ).…”

The role of PD-1/PD-L1 signaling pathway in cancer pathogenesis and treatment: a systematic review

“…In the case of metastatic tumors with greater than 50% PD-L1 expression, pembrolizumab can be used as the first-line treatment, while nivolumab is the drug of choice for secondline treatment, regardless of PD-L1 expression [59] . It is noteworthy that higher PD-L1 expression is generally linked to better results of ICI therapy [60] , yet burdens always lie ahead. Low RR and survival of patients going through ICI therapy, specifically those with metastatic and advanced NSCLC, created new urges for medicine [61] .…”

“…Combinational therapy is the next solution. Chemotherapy, the very basic and wellknown treatment strategy for cancer, has shown improved results in combination with pembrolizumab [60] . A study conducted recently reported meaningful improvement in objective RR and progression-free survival (PFS) after using tiragolumab in combination with atezolizumab compared to atezolizumab alone [64] .…”