Optimizing tissue adequacy for next-generation sequencing in small biopsies and fine-needle aspirations for nonsmall cell lung cancer: a root cause analysis and proposed solutions

Abstract

Introduction

Molecular testing is essential for managing advanced nonsmall cell lung cancer, yet up to 40% of biopsies can be inadequate due to insufficient tissue. This study aimed to identify causes of inadequate sampling through fine needle aspiration (FNA) and core needle biopsy (CNB) and propose solutions.

Materials and methods

We analyzed 96 patients undergoing endobronchial ultrasound (EBUS)-guided FNA or CNB for nonsmall cell lung cancer, alongside 44 patients with CT-guided CNB. All patients were tested using the MayoComplete Solid Tumor Panel, a comprehensive next-generation sequencing assay. A root cause analysis identified factors affecting tissue adequacy, such as needle size, pass numbers, and specimen types.

Results

Among EBUS biopsies, 35.3% of cases with FNA smears were inadequate, compared to 20% for CNB alone. The combination of both smears and tissue cores had the highest adequacy rate, with only 11.4% inadequacy for next-generation sequencing. We investigated the discrepancy between lymph nodes and lung tissue by examining nonpulmonary lymph nodes, liver, and soft tissue biopsies. Lymph node CNB had a 30% inadequacy rate, while liver and soft tissue showed 14.3% and 15.4%, indicating that lymph node heterogeneity may affect tissue adequacy. For CT-guided CNB, cases with 5 or more passes showed 85% adequacy, increasing to 100% with over 7 passes.

Conclusions

Combining CNB with EBUS FNA improves sample adequacy, especially for lymph nodes. We recommend these approaches to optimize tissue yield for molecular testing, aiding timely therapy initiation and reducing repeat biopsies. Smaller gene panels may also be useful when tissue is limited.