Liquid Biopsy in Early-Stage Lung Cancer: Current and Future Clinical Applications

Abstract

Lung cancer remains the leading cause of cancer death worldwide, with the majority of cases diagnosed in an advanced stage. Early-stage disease non-small cell lung cancer (NSCLC) has a better outcome, nevertheless the 5-year survival rates drop from 60% for stage IIA to 36% for stage IIIA disease. Early detection and optimized perioperative systemic treatment are frontrunner strategies to reduce this burden. The rapid advancements in molecular diagnostics as well as the growing availability of targeted therapies call for the most efficient detection of actionable biomarkers. Liquid biopsies have already proven their added value in the management of advanced NSCLC but can also optimize patient care in early-stage NSCLC. In addition to having known diagnostic benefits of speed, accessibility, and enhanced biomarker detection compared to tissue biopsy, liquid biopsy could be implemented for screening, diagnostic, and prognostic purposes. Furthermore, liquid biopsy can optimize therapeutic management by overcoming the issue of tumor heterogeneity, monitoring tumor burden, and detecting minimal residual disease (MRD), i.e., the presence of tumor-specific ctDNA, post-operatively. The latter is strongly prognostic and is likely to become a guidance in the postsurgical management. In this review, we present the current evidence on the clinical utility of liquid biopsy in early-stage lung cancer, discuss a selection of key trials, and suggest future applications.

Digital Profiling of Tumor Extracellular Vesicle-associated RNAs Directly from Unprocessed Blood Plasma

“…S27 ). This represents a substantial improvement, particularly for early-stage patients with low mutant allele frequencies, over FDA-approved blood-based tests relying on qPCR, ddPCR, or NGS, which analyze cell-free DNA (cfDNA) in peripheral blood ( 48 ). Notably, the mutation rate remained consistent across different stages, aligning with existing literature reporting similar EGFR mutation rates between earlyLstage and advancedLstage groups ( 49, 50 ).…”

Clinical Applications of Comprehensive Genomic Profiling in Advanced Non-Small-Cell Lung Cancer—A Case Series

“…Developments in precision oncology have prompted the evaluation of novel diagnostic tools to overcome some of the limitations of traditional tumor genotyping. The minimally invasive liquid biopsy techniques allow real-time biomolecular characterization of the tumor through the analysis of human body fluids [ 12 ]. In the current case series, we presented six patient scenarios in which tumor molecular profile was assessed in real time and how CGP results were integrated with other clinical data to aid the management of patients with advanced NSCLC.…”