Bridging East and West: Real-World Clinicogenomic Landscape of Metastatic NSCLC in Türkiye.

BACKGROUND/

OBJECTIVES

Genomic profiling guides treatment in metastatic non-small-cell lung cancer (mNSCLC), yet country-level data from Türkiye remain limited.

METHODS

We retrospectively analyzed consecutive patients with mNSCLC diagnosed between January 2018 and March 2025 across tertiary centers in all seven regions. Variables included demographics, smoking, histology, testing modality (single-gene vs. next-generation sequencing [NGS]), targetable genomic alterations (TGAs) and co-mutations, and programmed death-ligand 1 (PD-L1) tumor proportion score.

RESULTS

Among 1023 patients (mean age 64 years; 76.4% male), tobacco exposure was frequent (mean 42.1 pack-years); 16.9% were never-smokers. NGS use increased over time, exceeding 90% by 2025. TGAs were detected in 28.3% (EGFR 16.0%, ALK 5.0%, KRAS G12C 2.6%, BRAF V600E 3.2%; ROS1, MET exon 14, HER2, NTRK ≤ 2.5%; no RET). EGFR alterations occurred in 19% of non-squamous carcinomas and 6% of squamous cell carcinomas (SCCs), suggesting an intermediate East-West pattern. Among NGS-tested samples, TP53 was the most frequent co-mutation (33.1%), followed by alterations in CDKN2A, PIK3CA, FGFR, STK11, and KEAP1.

CONCLUSIONS

In this large, multicenter Turkish real-world cohort, the TGA spectrum broadly mirrors global patterns while revealing local nuances; EGFR mutations were more frequent than expected in SCC, and nationwide NGS adoption is accelerating. Limitations include retrospective design, non-centralized PD-L1 testing, and missing data. Prospective, standardized studies integrating outcomes and resistance mechanisms are warranted to refine regional precision oncology.