Prognostic value of preoperative ctDNA and pathological venous invasion for recurrence in EGFR-mutated non-small cell lung cancer

INTRODUCTION: Curative surgery followed by adjuvant osimertinib according to pathological stage (pStage) is standard for resectable epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC). Nevertheless, recurrence remains a concern even in Stage IA, for which adjuvant osimertinib is not indicated. We evaluated the utility of circulating tumor DNA (ctDNA) to predict recurrence in patients with resected pStage I-III EGFR-mutated NSCLC and examined prognostic value of preoperative biomarkers and pathological features. METHODS: Between January 2017 and May 2020, 382 patients with lung tumors underwent surgery at Kanazawa University Hospital, including 88 with NSCLC harboring common EGFR mutations. Preoperative ctDNA was analyzed using droplet digital PCR, targeting EGFR mutations. Patients were followed for up to 6.4 years, and disease-free survival (DFS) and overall survival (OS) were evaluated. RESULTS: Preoperative ctDNA positivity was detected in 26.1 % and venous invasion in 39.8 %. ctDNA-positive patients had lower 60-month DFS (54.1 % vs. 84.1 %; HR = 3.25; 95 % CI, 1.13-9.21; p = 0.028) and 60-month OS (65.1 % vs. 95.9 %; HR = 6.10; 95 % CI, 1.11-33.46; p = 0.037). Venous invasion was independently associated with poorer DFS (HR = 8.73; 95 % CI, 1.81-41.93; p = 0.0068). In combined analyses, no recurrences occurred in the double-negative, whereas the double-positive had a lower 60-month DFS than the single-positive (HR = 3.61; 95 % CI, 1.19-10.93; p = 0.023). CONCLUSION: Preoperative ctDNA detection and pathological venous invasion provide complementary prognostic information, and venous invasion is an independent predictor of recurrence risk in EGFR-mutated NSCLC. Combined assessment may refine postoperative risk stratification and inform perioperative management.