Stratifying risk in oligoprogressive EGFR-mutated non-small cell lung cancer (NSCLC): The role of liquid biopsy

Background EGFR-TKIs have markedly enhanced outcomes for non-small cell lung cancer (NSCLC) patients, but resistance development is virtually inevitable. In the context of oligoprogressive disease (OPD), local treatments can target resistant clones while EGFR-TKIs maintain systemic control, potentially extending the duration of therapy. However, identifying patients who benefit from this combined approach remains unclear. Methods We conducted a retrospective study on advanced EGFR-NSCLC patients with OPD during TKI therapy, treated with local therapy and continued TKI. Serum liquid biopsies for ctDNA EGFR mutations were performed at oligoprogression. We assessed the effect of liquid biopsy status and relevant clinical variables on progression-free survival-2 (PFS2; OPD to progression), overall survival-2 (OS2; OPD to death), overall survival-1 (OS1; diagnosis to death) and time to TKI discontinuation (TTD; TKI initiation to discontinuation). Results Among 84 patients, 70 had liquid biopsies, with 56 % testing positive for ctDNA. A positive liquid biopsy was associated with worse PFS2 (4.99 vs. 11.73 months, p < 0.001), OS2, OS1 and TTD. In stratified analysis, CNS oligoprogression showed no PFS2 difference by liquid biopsy status, whereas non-CNS oligoprogression revealed a significant difference (5.13 vs. 13.70 months, p < 0.001). Univariate analysis linked shorter PFS1, CNS progression, poor PS, high carcinoembryonic antigen, and non-SBRT radiotherapy to worse PFS2, while multivariate analysis identified liquid biopsy positivity as the only independent factor. Conclusions Liquid biopsy status is a significant prognostic marker in extracranial EGFR-oligoprogressive NSCLC, suggesting its potential in identifying patients who may benefit from continued TKI and local therapies. Further prospective studies are warranted to confirm these findings and explore alternative treatment strategies for OPD.