September 15, 2026 | OncLive Staff
Liquid biopsy and tissue biopsy showed high concordance for detecting actionable EGFR mutations in patients with stage III non–small cell lung cancer (NSCLC), according to findings from the retrospective CONCORDANCE-2 study presented in a poster session at the 2026 IASLC World Conference on Lung Cancer (WCLC).¹ Among 231 patients with paired liquid biopsy and tissue biopsy results obtained within 60 days of each other around the time of stage III diagnosis, overall concordance for actionable EGFR mutation detection was 97% (95% CI, 95%-99%), with a positive predictive value (PPV) of 100% (95% CI, 48%-100%) and a negative predictive value (NPV) of 97% (95% CI, 95%-99%).
All discordant results were false-negative liquid biopsy findings; no false-positive liquid biopsy results were observed in the cohort. Positive percent agreement (PPA) was 42% (95% CI, 14%-70%), and negative percent agreement (NPA) was 100% (95% CI, 98%-100%).
How was the CONCORDANCE-2 study designed?
CONCORDANCE-2 was a retrospective observational study built on the InfinityAI Data Library, which integrates electronic health record and claims data from the ConcertAI Translational360 platform with genomic testing data from Guardant Health. Investigators identified adults with a stage III NSCLC diagnosis between January 2020 and May 2025 who had undergone both liquid biopsy and tissue biopsy testing for EGFR mutation status, including exon 19 deletion, exon 20 insertion, L858R, T790M, G719C, S768I, and L861Q within 60 days of each other, with no prior EGFR TKI exposure. From an initial pool of 32,924 patients with NSCLC in the database, sequential eligibility filtering yielded a final cohort of 231 patients with paired, valid EGFR results from both testing modalities. Primary end points were overall concordance, PPA, NPA, PPV, and NPV between liquid biopsy and tissue biopsy, along with turnaround time and testing methodology, assessed overall and by patient characteristics and circulating tumor DNA (ctDNA) levels
What were the baseline characteristics and mutation detection rates?
The cohort had a median age of 71 years (range, 38-80), was 55% male, and was predominantly White or Caucasian (74%), with limited representation of Asian patients (4%). Most patients had a smoking history (89%). Histology was adenocarcinoma in 40% of patients, squamous in 31%, and other or not otherwise specified in 29%, and stage distribution was 47% IIIA and 50% IIIB/IIIC. All liquid biopsy samples (100%) and 91% of tissue biopsy samples were assessed using next-generation sequencing, and liquid biopsy returned results in a median of 7 days (IQR, 6-9; mean, 8 days) from specimen collection, compared with a median of 31 days (IQR, 22-44; mean, 39 days) for tissue biopsy.
The actionable EGFR mutation positivity rate was 5% (n = 12 of 231) by tissue biopsy and 2% (n = 5 of 231) by liquid biopsy, rates investigators noted were consistent with those reported in a parallel real-world concordance study.2 Exon 19 deletion and L858R accounted for the majority of actionable alterations detected by both modalities: among the 12 tissue biopsy–positive cases, exon 19 deletion accounted for 6, L858R for 4, exon 20 insertions for 1, and G719C for 1; among the 5 liquid biopsy–positive cases, exon 19 deletion and L858R each accounted for 2, and exon 20 insertion for 1.
How did liquid biopsy performance vary by ctDNA tumor fraction and patient subgroups?
Investigators concluded that a positive liquid biopsy result reliably identified patients with EGFR-mutant disease and, given its substantially faster
ctDNA tumor fraction, measured by maximum variant allele frequency (MVAF) on liquid biopsy, emerged as a key determinant of test performance. Among the 106 patients with MVAF at or above the cohort median of 0.9%, PPA reached 100% (95% CI, 29%-100%), with no discordant results. Among the 99 patients with MVAF below the median, PPA fell to 33% (95% CI, 4%-78%), with liquid biopsy missing 4 of 6 tissue biopsy–positive cases.
Investigators reported no clear performance differences by gender, smoking history, disease stage, or histology, though they cautioned that subgroup interpretation was limited by small sample sizes and few mutation–positive cases in each stratum. The findings echo broader efforts to define when ctDNA-based testing is fit for purpose in solid tumors; a recent ASCO guideline on ctDNA testing in solid tumors and lymphoma similarly emphasized context-specific interpretation of liquid biopsy sensitivity.³
What are the clinical implications and limitations of the CONCORDANCE-2 findings?
Investigators concluded that a positive liquid biopsy result reliably identified patients with EGFR-mutant disease and, given its substantially faster turnaround time, may support earlier initiation of targeted therapy in unresectable stage III NSCLC.¹ A negative liquid biopsy result, however, requires confirmatory tissue biopsy testing before ruling out an actionable EGFR mutation, particularly in patients with low ctDNA tumor fraction, where false-negative risk was highest.
The retrospective design, reliance on real-world EHR and claims data, and small number of mutation-positive cases within some subgroups limit the precision of the reported estimates, and the cohort’s limited Asian representation (4%) constrains generalizability to populations with a higher prevalence of EGFR alterations. These considerations align with recent real-world data on ctDNA-based testing in NSCLC, which similarly identified tumor fraction as a determinant of test sensitivity for identifying disease that liquid biopsy alone may miss.⁴
References
Rolfo C, Power MC, Liao J, et al. CONCORDANCE-2: concordance of EGFR mutation detection by liquid biopsy versus tissue biopsy in patients with stage III non-small cell lung cancer. Presented at: International Association for the Study of Lung Cancer (IASLC) 2026 World Conference on Lung Cancer; September 12-15, 2026; Seoul, South Korea. Abstract P2.123.
Malapelle U, Nasirova F, Wang A, et al. Liquid biopsy and tissue biopsy for the detection of EGFR mutations in patients with stage III non-small-cell lung cancer: an observational real-world study. ESMO Open. 2026;11(1):106029. doi:10.1016/j.esmoop.2025.106029
ASCO issues first guideline on ctDNA testing in solid tumors and lymphoma. OncLive. Published August 21, 2026. Accessed September 15, 2026. https://www.onclive.com/view/asco-issues-first-guideline-on-ctdna-testing-in-solid-tumors-and-lymphoma
ctDNA MRD testing helps predict outcomes in NSCLC. OncLive. Published July 29, 2026. Accessed September 15, 2026. https://www.onclive.com/view/ctdna-mrd-testing-helps-predict-outcomes-in-nsclc
