Real-world adoption of comprehensive genomic profiling in a national cohort of patients with resected stage I–III non–small cell lung cancer.

Abstract

8043 Background: Comprehensive genomic profiling (CGP) is increasingly used in the multidisciplinary management of resectable NSCLC to identify candidates for targeted adjuvant therapies and clinical trials. NCCN and Veterans Affairs (VA) guidelines recommend selective – not universal – testing in early-stage disease, yet real-world use after surgery remains poorly described. Using the VA’s highly unique National Precision Oncology Program (NPOP), we evaluated trends in CGP uptake, factors associated with testing, and the biomarker landscape in early-stage NSCLC. Methods: We performed a retrospective cohort study of patients with resected pathologic stage I–III NSCLC (2019-2025) within the VA. CGP was defined as next-generation sequencing (NGS) of the primary tumor within 3 months of surgery. We assessed frequency of CGP and clinicodemographic factors associated with GCP via multivariable logistic regression. We also assessed the distribution of potentially actionable genomic alterations. Results: A total of 6,605 patients were included (4,686 [70.9%] stage I; 1,255 [19.0%] stage II; 664 [10.1%] stage III). Over the study period, 1,337 (20.2%) patients received NGS testing. CGP utilization increased over time (11.4% in 2019 to 25.8% in 2025), paralleling evolving recommendations regarding adjuvant targeted therapies. Of note, the GCP utilization rate among those with stage Ib-III NSCLC in 2025 was 54.9%. In multivariable models, factors associated with higher CGP use included former smoking status (adjusted hazard ratio [aHR] 1.19, 95% CI 1.02-1.40), never smoking status (aHR 1.31, 95% CI 1.05-1.65), robotic resection (aHR 1.82, 95% CI 1.52-2.18), higher stage (stage II: aHR 4.33, 95% CI 3.72-5.04; stage III: aHR 5.79, 95% CI 4.81-6.98), and more recent treatment year (aHR 1.25, 95% CI 1.20-1.30). Median time from surgery to CGP ordering was 25 days (IQR 10-67). Among tested tumors, key genomic alterations included EGFR exon 19 deletions (2.39%) and L858R (1.20%), ALK fusions (0.52%), KRAS G12C (10.62%), MET exon 14 skipping (2.02%), ERBB2 mutations (3.29%), BRAF V600E (1.05%), and ROS1 fusions (0.53%). Conclusions: In this national cohort, CGP use after resection of stage I–III NSCLC increased substantially over time, likely supported by the VA NPOP infrastructure. Testing patterns were largely guideline-concordant, with continued uptake within complex multidisciplinary pathways. These findings reinforce the real-world adoption of genomically informed decision-making in early-stage disease while highlighting opportunities to strengthen implementation and promote wide access to precision oncology.