Prognostic Value of STAS, Lymph Node Metastasis, and VPI in NSCLC ≤ 4 cm Treated with Lobectomy

Background/Objectives: This study aimed to evaluate the prognostic effects of tumor spread through air spaces (STAS) and other clinical and pathological risk factors on disease-free survival (DFS) in patients with non-small cell lung cancer (NSCLC) who underwent curative lobectomy and had tumors measuring 4 cm or less. Methods: NSCLC patients who underwent surgery between March 2015 and May 2024 and had at least 12 months of follow-up were retrospectively analyzed. Patients with tumors measuring 4 cm or less who underwent R0 resection, lobectomy, and STAS assessment on intraoperative frozen sections were included in the study. Clinicopathological features of all patients were restaged according to the 9th edition of the TNM staging system. The Kaplan-Meier method, log-rank test, and univariate Cox regression analysis were used to determine the factors affecting DFS. Results: 88 patients were included in the study. The median age of the patients was 61 years, 77.3% were male, and 72.7% had adenocarcinoma histology. According to TNM 9, 23.9% of the cases were staged T1b, 18.2% T1c, and 58.0% T2a. STAS positivity was detected in 45 patients (51.1%). The rates of lymphovascular invasion (LVI) (40.0% vs. 18.6%; p = 0.028) and visceral pleural invasion (VPI) (57.8% vs. 27.9%; p = 0.005) were significantly higher in the STAS-positive group than in the STAS-negative group. Recurrence was observed in a total of 31 patients (35.2%) during a median follow-up period of 68.1 months. In Kaplan-Meier analysis, the median DFS was not reached for the entire cohort. The estimated median DFS in STAS-positive patients was 52.7 months, while the median was not reached in the STAS-negative group (p = 0.001). The median DFS was 52.3 months in those with lymph node positivity, while the median was not reached in those with lymph node negativity (p = 0.031). According to TNM 9, the difference in DFS between stage IA/IB and stage IIAB groups was not statistically significant (p = 0.080). In univariate Cox analysis, STAS positivity (HR = 3.79; 95% CI: 1.69-8.51; p = 0.001), lymph node positivity (HR = 2.58; 95% CI: 1.05-6.31; p = 0.038) and VPI (HR = 2.28; 95% CI: 1.07-4.86; p = 0.032) were found to be significant prognostic factors adversely affecting DFS. Age, gender, histological type, tumor location, T stage, LVI, perineural invasion (PNI), and adjuvant chemotherapy had no significant effect on DFS. Conclusions: STAS is a strong negative prognostic indicator for recurrence in patients with operated NSCLC with tumor size ≤ 4 cm. It is believed that STAS should be integrated into risk-based staging and adjuvant treatment decision-making processes in early-stage NSCLC, particularly when evaluated in conjunction with VPI and lymph node positivity.