STAS beim NSCLC: Risikomarker für Rezidiv und Prognose?

Impact of Preoperative Diagnostic Biopsy Procedure on Spread Through Airspaces and Related Outcomes in Resected Stage I Non-Small Cell Lung Cancer

The choice of surgical procedure for early-stage non-small cell lung cancer (NSCLC) with tumour spread through air spaces (STAS) remain debated. This study aimed to analyse the prognostic influence of STAS on thoracoscopic segmentectomy compared to lobectomy for clinical stage I NSCLC. This retrospective study included prospectively collected data of consecutive patients who underwent thoracoscopic segmentectomy or lobectomy for clinical stage I NSCLC from September 2020 to September 2023 at a high-volume hospital. We assessed overall survival (OS) and recurrence-free survival (RFS) using Kaplan-Meier estimator with log-rank test. LASSO-Cox and Cox regression analyses identified independent factors for survivals of STAS presence. Among the 785 patients in the study, 151 (19.2%) had STAS-positive NSCLC. No significant difference was observed in OS and RFS between patients with the presence and absence of STAS, nor between those undergoing thoracoscopic segmentectomy and lobectomy for NSCLC in the absence of STAS. Whereas worse survivals were found in segmentectomy for patients with STAS when compared to lobectomy (3-year OS: 58.4% vs 89.0%, P < 0.001; 3-year RFS: 69.8% vs 82.7%, P < 0.001). On multivariable analysis, segmentectomy (vs. lobectomy) and increased maximum standardized uptake value in positron emission tomography were independent prognostic factors of OS (hazard ratio [HR] 5.81, P = 0.010; HR 1.12, P = 0.022) and RFS (HR 5.78, P = 0.004; HR 1.10, P = 0.025) among patients with STAS. In this study, segmentectomy for clinical stage I NSCLC with STAS had inferior RFS and OS when compared to lobectomy.

Tumor spread through air spaces (STAS) and lymphovascular invasion (LVI) have been associated with poor prognosis in stage I non-small cell lung cancer (NSCLC). This study aimed to evaluate the prognostic significance of STAS and LVI, and to investigate the impact of adjuvant chemotherapy (ACT) on survival outcomes in this patient population. A retrospective cohort study was conducted including 392 patients with pathological stage I NSCLC who underwent surgical resection at two Kaohsiung Medical University-affiliated hospitals between 2016 and 2019. Patients were stratified into three groups: STAS-positive without LVI (STAS + LVI-), STAS-positive with LVI (STAS + LVI+), and STAS-negative (STAS-). Survival outcomes were analyzed using Kaplan-Meier methods and Cox proportional hazards models. Associations between tumor size, STAS, and LVI were evaluated using chi-square tests. STAS was identified in 101 patients (25.8%), of whom 20 (19.8%) also exhibited LVI. The prevalence of both STAS and LVI increased significantly with tumor size (p < 0.0001 for both). STAS positivity was independently associated with inferior recurrence-free survival (RFS) (hazard ratio [HR] = 2.33, p = 0.021). Overall, ACT did not significantly improve survival in STAS-positive patients (p = 0.63). However, among patients with concurrent STAS and LVI, a trend toward improved 5-year RFS was observed with ACT (54.5% vs. 44.4%; p = 0.43). In contrast, ACT was associated with significantly worse RFS in STAS-negative patients (p = 0.024). STAS represents an independent adverse prognostic factor in stage I NSCLC, and conventional ACT appears to offer limited benefit in this group overall. Patients harboring both STAS and LVI may derive potential benefit from ACT, whereas STAS-negative patients may require careful evaluation to avoid overtreatment. These findings support the need for personalized, risk-adapted postoperative management strategies and warrant further prospective investigation.

Lobectomy (LOB) remains the standard treatment for stage I non-small cell lung cancer (NSCLC), though sublobar resection (SLR) has emerged as a potential alternative with comparable outcomes. Spread through air spaces (STAS) has been confirmed as an independent risk factor after lung cancer surgery. The prognosis differences between LOB and SLR in patients with stage I NSCLC with STAS are controversial. After systematic retrieval across multiple databases, 25 eligible studies involving 14,126 patients were identified. We extracted hazard ratios (HRs) for recurrence-free survival (RFS) and overall survival (OS) comparing lobectomy versus sublobar resection, along with reconstructed individual patient data (IPD) and adjuvant chemotherapy (ACT) records. These datasets were subsequently subjected to meta-analysis with complementary subgroup and sensitivity analyses. STAS was confirmed as an independent risk factor (RFS: HR 2.61, 95% CI 2.17-3.14; OS: HR 2.15, 95% CI 1.75-2.63). In subgroup analysis of SLR versus LOB in patients with STAS, the inferior RFS and comparable OS were observed in the SLR group (RFS: HR 1.70, 95% CI 1.16-2.49, n = 3488; OS: HR 1.10, 95% CI 0.83-1.46, n = 3581). Furthermore, ACT following SLR effectively reduced recurrence risk in STAS-positive patients compared with LOB (LOB: RFS: HR 1.03, 95% CI 0.48-2.22; SLR: RFS: HR 0.44, 95% CI 0.23-0.82). Surgical approach significantly impacts survival outcomes in stage I NSCLC patients with STAS. LOB remains the preferred option due to its lower recurrence rate and prolonged survival outcomes; for high-risk patients undergoing SLR, ACT is recommended in the case of postoperative STAS.

This study aimed to elucidate the clinicopathological significance of spread through air space (STAS) in non-small cell lung cancer (NSCLC) through a meta-analysis. Using 47 eligible studies, we obtained the estimated rates of STAS in various histological subtypes of NSCLC and compared the clinicopathological characteristics and prognosis between NSCLC with and without STAS. The estimated STAS rate was 0.368 (95% confidence interval [CI], 0.336–0.0.401) in patients with NSCLC. Furthermore, the STAS rates for squamous cell carcinoma and adenocarcinoma were 0.338 (95% CI, 0.273–0.411) and 0.374 (95% CI, 0.340–0.409), respectively. Among the histological subtypes of adenocarcinoma, micropapillary-predominant tumors had the highest rate of STAS (0.719; 95% CI, 0.652–0.778). The STAS rates of solid- and papillary-predominant adenocarcinoma were 0.567 (95% CI, 0.478–0.652) and 0.446 (95% CI, 0.392–0.501), respectively. NSCLCs with STAS showed a higher visceral pleural, venous, and lymphatic invasion than those without STAS. In addition, anaplastic lymphoma kinase mutations and ROS1 rearrangements were significantly more frequent in NSCLCs with STAS than in those without STAS. The presence of STAS was significantly correlated with worse overall and recurrence-free survival (hazard ratio, 2.119; 95% CI, 1.811–2.480 and 2.372; 95% CI, 2.018–2.788, respectively). Taken together, the presence of STAS is useful in predicting the clinicopathological significance and prognosis of patients with NSCLC.

Tumor Spread through Air Spaces Affects the Recurrence and Overall Survival in Patients with Lung Adenocarcinoma >2 to 3 cm

Tumor Spread Through Air Spaces in Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis

Tumor spread through air space (STAS) is a novel pattern of invasion related to poor prognosis in non-small cell cancer (NSCLC). Nevertheless, little is known about the role of STAS in small cell lung cancer (SCLC). We sought to determine whether STAS has a significant effect on recurrence among SCLC patients. We collected clinical and follow-up information from 181 resected stage I-III SCLC patients and compared overall survival (OS) and disease-free survival (DFS) between the patients with or without STAS using the Kaplan‒Meier method. To explore the effect of STAS on recurrence, a competing-risk analysis was conducted. Among 181 SCLC patients, STAS was observed in 56 (30.94%) patients, and 125 (69.06%) patients did not have STAS. Furthermore, 33 (18.23%) patients had recurrence, including 12 patients with brain metastases. Patients with STAS had worse DFS. The cumulative incidence of any recurrence was higher in patients with STAS than in those without STAS. Univariate and multivariate competing-risk regression analyses revealed that sublobar resection and STAS were independent risk factors for SCLC recurrence (p = 0.009 and p = 0.029 for multivariate analysis, respectively). SCLC patients with STAS have worse DFS than SCLC patients without STAS. STAS is an independent prognostic factor in SCLC patients.

P56.03 Prognostic Value of Tumor Spread Through Air Spaces in Patients With Lung Adenocarcinoma after Radical Surgery

Spread Through Air Spaces in Residual Tumor Classification for Clinical IA Lung Adenocarcinoma

Aim: Lung cancer is the leading cause of cancer-related mortality worldwide. Spread through air spaces (STAS) refers to tumor cells found within air spaces surrounding the main tumor mass and has been associated with poor prognosis. This study aimed to investigate the relationship between STAS positivity and clinical as well as pathological variables in operated non-small cell lung cancer (NSCLC) patients followed at our center. Material and Methods: Patients diagnosed with NSCLC who underwent surgery between January 2018 and May 2022 at our institution were retrospectively analyzed. The relationship between clinical and pathological variables and STAS was investigated. Survival analyses were performed using the Kaplan-Meier method. Results: A total of 85 cases were evaluated within the scope of the study. STAS positivity was observed in 64.7% (n=55) of patients. Low-grade tumors were less common in the STAS positive group (p = 0.006). Regarding lymph node involvement, the frequency of N2 disease was significantly higher in STAS positive patients compared to STAS negatives (p = 0.003). The presence of lymphovascular invasion (LVI) was also significantly higher in the STAS positive group (p = 0.011). Although disease-free survival (DFS) and overall survival (OS) were numerically higher in the STAS negative group, the difference was not statistically significant. Conclusion: In this study, a significant association was found between STAS positivity and N2 disease, grade, and LVI in patients diagnosed with NSCLC. Although survival times were found to be lower in STAS positive patients compared to the STAS negative group, this difference did not reach statistical significance.

<title>Abstract</title> Objective In patients with Non-Small Cell Lung Cancer (NSCLC), spread through air spaces (STAS) describes tumor cells within alveolar spaces beyond the main tumor margin and is considered an invasive pattern associated with recurrence. This study aimed to preoperatively predict STAS using metabolic parameters obtained from F-18 FDG PET/CT imaging. Methods This retrospective single-center study analyzed 108 patients who underwent surgical resection between 2019 and 2024. Histological assessment determined the presence and subtype of STAS as limited or extended. PET/CT parameters included SUVmax, MTV, and TLG, measured by both a fixed threshold (42% of SUVmax) and patient-specific adaptive thresholds. Peritumoral rim values were calculated volumetrically. Variables associated with STAS in univariate analysis were tested with ROC analysis to determine diagnostic performance, and survival outcomes were evaluated using the Kaplan–Meier method. Results STAS was detected in 56.5% (n = 61) of patients, with the extended subtype observed in 67.2% (n = 41) of these cases. SUVmax was significantly higher in STAS-positive tumors and demonstrated modest discriminative ability, with an AUC of 0.619. A cut-off value of 5.3 achieved very high sensitivity (0.97) but only moderate specificity (0.64). None of the volumetric parameters, including MTV and TLG, differentiated between limited and extended STAS. Survival was numerically worse in patients with STAS, and extended STAS tended to have shorter median overall survival compared with limited STAS, though these differences did not reach statistical significance. Conclusion It was concluded that STAS, which plays a crucial role in the management of lung cancer treatment and prognosis prediction, can be predicted by SUVmax and may serve as a useful non-invasive parameter in the preoperative evaluation. However, other volumetric parameters showed no significant predictive value, and the high sensitivity but moderate specificity of SUVmax limit its standalone clinical utility. Future studies combining metabolic, radiomic, and morphological features may yield more accurate tools for preoperative STAS detection and tailored surgical planning.

Spread through air spaces (STAS) is a poor prognostic factor for lung adenocarcinoma, particularly in patients undergoing limited resection, and its accurate prediction can improve the patient outcomes. This study evaluated the impact of STAS on the surgical outcomes and predictive factors. We analyzed 511 patients with clinical stage IA lung adenocarcinoma who underwent curative resection between 2007 and 2022. STAS was assessed histologically, and logistic regression was used to identify the predictors. The recurrence-free and overall survival rates were also evaluated. Among the patients, 27.8% had STAS with significantly poor 5-year recurrence-free survival (65.6% vs. 88.5% in STAS-positive vs.-negative cases, respectively), particularly in patients treated with sublobar resection. STAS was an independent, poor prognostic factor for the recurrence-free survival in the sublobar group but not in the lobectomy group. Elevated serum carcinoembryonic antigen (≥ 5.8ng/mL), consolidation tumor ratio (≥ 0.9), and SUVmax (≥ 2.3) were independent predictors. STAS positivity increased with the number of risk factors as follows: 8.0% (none), 27.1% (one), 38.5% (two), and 60.4% (all three). The prediction of STAS using carcinoembryonic antigen levels, consolidation tumor ratio, and SUVmax can guide surgical decision-making and facilitate the provision of individualized treatment strategies for stage IA lung adenocarcinoma.

Prognostic Impact of Margin Distance and Tumor Spread Through Air Spaces in Limited Resection for Primary Lung Cancer

The International Association for the Study of Lung Cancer (IASLC) pathology panel has proposed a new grading system for invasive lung adenocarcinoma (LADC). This study aims to validate this novel grading system for invasive LADC using propensity score matching (PSM), with a specific focus on patients exhibiting spread through air space (STAS). We retrospectively analyzed the clinicopathologic features of a large cohort of 910 non-mucinous LADCs with STAS from 2017 to 2020 and classified them according to the novel grading system. We applied PSM to adjust for potential confounders between the grading groups. Kaplan-Meier and Cox proportional hazards models were adopted for prognostic evaluation. The results showed that the IASLC grading system (grades 2 and 3) stratified well in terms of recurrence-free survival (RFS) and overall survival (OS) (P=0.02 and P=0.02, respectively) after matching, with Grade 3 being an independent predictor of RFS [hazard ratio (HR), 1.533; P=0.02] and OS (HR, 2.765; P=0.02) in multivariable models. The concordance index (C-index) and area under the curve (AUC) of the IASLC system were 0.719 and 0.754 for recurrence and 0.844 and 0.891 for death, respectively. In addition, anaplastic lymphoma kinase (ALK) fusion and tumor protein p53 (TP53) mutations were detected more frequently in grade 3 tumors, while epidermal growth factor receptor (EGFR) mutations were more prevalent in grade 2 tumors. The IASLC grade did not predict the benefit of adjuvant chemotherapy (ACT). This study suggests that the new IASLC grading system is a valuable prognostic tool for patients with STAS-positive LADC.