Liquid Biopsy as a Primary Diagnostic Triage for EGFR-Mutated NSCLC in Resource-Limited Settings: A Systematic Review

Abstract

Background of study: Lung cancer remains a leading cause of cancer-related mortality in Indonesia, where geographic and infrastructural constraints frequently delay tissue-based molecular diagnosis. Although tissue biopsy is the gold standard for detecting epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC), it is invasive and often limited by inadequate samples and tumor heterogeneity.

Aims or objectives: This systematic review evaluates the diagnostic concordance between liquid biopsy using circulating tumor DNA (ctDNA) and tissue biopsy for EGFR mutation detection and assesses its feasibility as a primary diagnostic triage modality in resource-limited settings.

Methods: A systematic search of PubMed, Wiley Online Library, and SAGE Journals was conducted for paired diagnostic studies published between 2020 and 2026. Ten eligible studies were included, and methodological quality was assessed using the QUADAS-2 tool.

Result: A total of 1,458 patients were analyzed. Diagnostic concordance between plasma ctDNA and tissue biopsy ranged from 56.1% to 100%. High-sensitivity platforms, including next-generation sequencing and droplet digital polymerase chain reaction, demonstrated superior performance. Specificity was consistently high (>90%), whereas sensitivity varied widely (34.6%–100%) and was influenced by tumor stage and metastatic burden.

Conclusion: Liquid biopsy demonstrates high diagnostic validity and logistical feasibility as an initial screening approach. A liquid-first diagnostic algorithm, with reflex tissue biopsy in negative cases, may improve access to precision oncology while preserving diagnostic safety in resource-limited healthcare systems.