The Importance of a Satisfactory Biopsy for the Diagnosis of Lung Cancer in the Era of Personalized Treatment

Abstract

Advances in molecular biology are improving the understanding of lung cancer and changing the approach to treatment. A satisfactory biopsy that allows for histologic characterization and mutation analysis is becoming increasingly important. Most patients with lung cancer are diagnosed at an advanced stage, and diagnosis is often based on a small biopsy or cytology specimen. Here, we review the techniques available for making a diagnosis of lung cancer, including bronchoscopy, ultrasound-guided bronchoscopy, mediastinoscopy, transthoracic needle aspiration, thoracentesis, and medical thoracoscopy. We also discuss the indications, complications, and tissue yields of those techniques, especially as they pertain to testing for molecular markers. KEY WORDSLung cancer, diagnosis, bronchoscopy, endobronchial ultrasonography, thoracoscopy, transthoracic needle aspiration, molecular markers, EGFR INTRODUCTIONDiscoveries in molecular biology are changing the approach to the treatment of patients with non-smallcell lung cancer (nsclc). In recent years, the histologic characterization of lung cancer has markedly advanced, moving beyond the simple distinction of small-cell or non-small-cell disease.The observation that certain histologic subtypes respond differently to particular chemotherapeutic agents and the increasing use of targeted therapies have created a need for precise histologic characterization of biopsy specimens. For example, several trials have shown that response rate and survival with pemetrexed are significantly better in patients with non-squamous histology [1][2][3] . Trials using tyrosine kinase inhibitors have observed that greater benefit from treatment with those agents is seen in patients with nsclc tumours harbouring EGFR mutations than in patients with wild-type tumours 4 . Ongoing clinical trials are examining the use of Alk inhibitors in patients with nsclc characterized by EML4-ALK gene translocations 5 . Those mutations are found almost exclusively in adenocarcinomas.Lung cancer remains the leading cause of cancer death in North America. In Canada in 2010, an estimated 25,300 Canadians were diagnosed with lung cancer, and 20,600 died of the disease 6 . At diagnosis, 75% of patients have either locally advanced or metastatic disease 7 . The goal in this latter group of patients is to establish the diagnosis and, ideally, to confirm the disease stage with the least invasive technique possible. As a result, biopsy specimens have become increasingly smaller. Of nsclc patients receiving chemotherapy for advanced disease, 80% will have only a small biopsy specimen or cytology samples available for diagnosis 8 .In this review, we discuss the minimally invasive and invasive techniques available for the diagnosis and staging of lung cancer, with their success rates and complications. We also discuss the size of the tissue samples obtained by the various techniques, as that size pertains to maximizing the histologic characterization of lung cancer in an era of personalized medicine. Lastly, we re...

Liquid biopsy as a follow‐up tool: Comment on longitudinal monitoring of somatic genetic alterations in circulating cell‐free DNA during treatment with epidermal growth factor receptor–tyrosine kinase inhibitors

“…A major issue in the management of non–small cell lung cancer (NSCLC) is the relative lack of availability of these samples (ie, small histological biopsies and cytological specimens) for morphological, immunohistochemistry, and molecular analysis . In addition to the limitations of these paucicellular specimens, up to 30% of NSCLC patients do not have tissue availability due to poor general conditions or technical and medical limitations .…”

Diagnostic Challenges in Non-Small-Cell Lung Cancer: An Integrated Medicine Approach

“…Pulmonologists, interventional radiologists or surgeons will need to obtain samples of sufficient quality and quantity for both histologic diagnosis and molecular analysis. Core biopsies are preferred, where four specimens from central lesions may be adequate for diagnosis, but up to six may need to be considered for detailed molecular analysis [70]. For patients with advanced disease where resected tumor samples may not be available, tissue for tumor typing and molecular analysis can be obtained by a number of non-invasive techniques, where optimization of tissue recovery and minimization of procedure-related morbidity are crucial [71].…”

Cell free DNA analysis by SiRe® next generation sequencing panel in non small cell lung cancer patients: focus on basal setting

“…To date according to the European Medicines Agency guidelines, in patients without tissue availability, only for EGFR TKIs treatment decision making, cell-free DNA (cfDNA) can be used as a fast and non-invasive surrogate for EGFR mutational testing (9)(10)(11)(12)(13). However, the assessment of 1 gene mutations in cfDNA is challenging, in particular in basal setting, for the detection of first and second TKIs generation EGFR sensitizing mutations, due to the very low concentration of circulating tumor DNA, that represent only a small fraction of the total cfDNA (9,10,(12)(13)(14)(15). Thus, the clinical implementation of next generation techniques, such as next generation sequencing (NGS) or digital PCR (dPCR) based assay is crucial (9,10,12,13,16,17).…”

“…Diagnostic samples are frequently scarcely cellular, being represented by either cytological specimens or small tissue endoscopic biopsies; these limited tissue samples often may be not sufficient for epidermal growth factor receptor (EGFR) and other clinical relevant biomarkers, such as ALK translocation and PD-L1 expression, whose assessment is required to select patients for first line treatment administration (1,2). In particular for EGFR tyrosine kinase inhibitors (TKIs), such as gefitinib, erlotinib and afatinib the identification of activating EGFR mutations in exon 18, 19 and 21 is mandatory before the first line treatment (3)(4)(5)(6)(7)(8).…”