BACKGROUND: Spread through air spaces (STAS) consists of lung cancer tumor cells that are identified beyond the edge of the main tumor in the surrounding alveolar parenchyma. It has been reported by meta-analyses to be an independent prognostic factor in the major histologic types of lung cancer, but its role in lung cancer staging is not established.
METHODS: To assess the clinical importance of STAS in lung cancer staging, we evaluated 4061 surgically resected pathologic stage I R0 NSCLC collected from around the world in the International Association for the Study of Lung Cancer database. We focused on whether STAS could be a useful additional histologic descriptor to supplement the existing ones of visceral pleural invasion (VPI) and lymphovascular invasion (LVI).
RESULTS: STAS was found in 930 of 4061 of the pathologic stage I NSCLC (22.9%). Patients with tumors exhibiting STAS had a significantly worse recurrence-free and overall survival in both univariate and multivariable analyses involving cohorts consisting of all NSCLC, specific histologic types (adenocarcinoma and other NSCLC), and extent of resection (lobar and sublobar). Interestingly, STAS was independent of VPI in all of these analyses.
CONCLUSIONS: These data support our recommendation to include STAS as a histologic descriptor for the Ninth Edition of the TNM Classification of Lung Cancer. Hopefully, gathering these data in the coming years will facilitate a thorough analysis to better understand the relative impact of STAS, LVI, and VPI on lung cancer staging for the Tenth Edition TNM Stage Classification.

UNASSIGNED: The T classification of non-small-cell lung cancer (NSCLC) was upgraded from T1 to T2 when accompanied by visceral pleural invasion (VPI). However, the association between VPI and prognostic outcomes was obscure in NSCLC patients with ≤3 cm tumor size (TS), which leaded the controversy of selection of T classification. The goal was to evaluate the effect of VPI on the prognosis of NSCLC with ≤ 3cm TS and present a modified T classification.
UNASSIGNED: A total of 14,934 NSCLC patients without distant metastasis were recruited through a retrospective study in the SEER database. The effect of VPI on lung cancer specific survival (LCSS) was evaluated using survival curve and COX regression analysis in NSCLC patients with ≤3 cm TS.
UNASSIGNED: Although there was no difference of the LCSS of PL0 and PL1 patients with ≤2 cm TS in patients without lymph node (LN) metastasis, the LCSS was lower in PL2 patients than those in PL0 (T1a: p < 0.001; T1b: p = 0.001). Moreover, the LCSS was decreased in PL1 and PL2 patients with 2-3 cm TS compared with PL0 (T1c: PL1, p < 0.001; PL2, p = 0.009) of patients without LN metastasis. No difference of LCSS was observed in patients with LN metastasis between PL0 with PL1 and PL2.
UNASSIGNED: In NSCLC patients without LN metastasis and TS ≤ 2 cm, tumor with PL1 should remain defined as T1, tumor with PL2 should be defined as T2. However, 2-3 cm TS patients with PL1 or PL2 should both defined as T2. Meanwhile, ≤3 cm TS patients with LN metastasis can be regarded as T1, whether NSCLC patients accompanied with PL1 or PL2.

OBJECTIVE: Visceral pleural invasion is an adverse prognostic factor in non-small-cell lung cancer, but its value in small-cell lung cancer remains unclear. Thus, we investigated the prognostic impact of visceral pleural invasion in patients with surgically resected small-cell lung cancer.
METHODS: We queried the Surveillance, Epidemiology and End Results Program database for patients diagnosed with stages I-III (excluding N3 and nodal metastasis cannot be evaluated (NX)) small-cell lung cancer from 2004 to 2016, who underwent surgery. To minimize unbalanced baseline characteristics between the visceral pleural invasion and non-visceral pleural invasion groups, one-to-one propensity score matching was employed. A Kaplan-Meier curve was used to compare the overall survival of the two cohorts. A Cox proportional hazards model was adopted to determine the impact of visceral pleural invasion on survival.
RESULTS: Of the 1416 patients included, 372 (26.27%) presented with visceral pleural invasion. Patients with visceral pleural invasion showed significantly worse overall survival (P < 0.001) both before and after propensity score matching. Multivariable analysis indicated that visceral pleural invasion was an independent adverse factor affecting survival. Patients with visceral pleural invasion showed poorer overall survival (hazard ratio: 1.44; 95% confidence interval: 1.17-1.76; P < 0.001). Subgroup analyses revealed that the non-visceral pleural invasion group was associated with favourable overall survival in N0 patients (P = 0.003) but not in N1 or N2 patients (P = 0.774 and 0.248, respectively). Patients diagnosed at younger ages, females, lower N stage, resection with a lobectomy and adjuvant chemotherapy were associated with improved overall survival in the visceral pleural invasion group.
CONCLUSIONS: Visceral pleural invasion was an indicator of a poor prognosis for small-cell lung cancer, especially in those with N0 disease. Adjuvant chemotherapy significantly improves patient outcomes for patients with visceral pleural invasion.

UNASSIGNED: In cases of peripheral lung cancer with visceral pleural invasion and severe pleural adhesion, the question arises as to whether video-assisted thoracoscopic surgery (VATS) is a safe operation. The purpose of this study was to evaluate whether whole pleural adhesion is a risk factor for recurrence of cancer when performing VATS lobectomy for stage I non-small cell lung cancer (NSCLC) with visceral pleural invasion.
UNASSIGNED: From 2010 to 2018, 123 consecutive patients who were diagnosed as stage I NSCLC with visceral pleural invasion and who underwent VATS lobectomy, were reviewed retrospectively. Those patients with partial pleural adhesion were excluded. The prognoses of the patients in the whole pleural adhesion group were compared with those of the non-adhesion group.
UNASSIGNED: The clinicopathological characteristics were not found to differ between the two groups, with the exception of age. The mean age of the whole pleural adhesion group was found to be greater than that of the non-adhesion group (70.6 vs. 64.4, P=0.002). The 5-year recurrence-free survival rates for the whole pleural adhesion group and the non-adhesion group were 64.8% and 70.9% respectively, and they were not statistically different (P=0.545). In multivariate analysis, the extent of lymph node dissection (hazard ratio =13.854, P=0.023) was a significant risk factor for recurrence. Whole pleural adhesion was not a risk factor for recurrence.
UNASSIGNED: Whole pleural adhesion was not a risk factor for recurrence after VATS lobectomy in stage I NSCLC with visceral pleural invasion. However, the extent of lymph node dissection was identified as an important prognostic factor.

Visceral pleural invasion (VPI) is considered an adverse prognostic factor in non-small cell lung cancer (NSCLC). However, the prognostic roles of VPI in Ⅲ/N2 NSCLC remain controversial. Therefore, this study aims to evaluate the prognostic value of VPI in patients with postoperative stage pT1-2N2M0 NSCLC.
Using the Surveillance, Epidemiology, and End Results (SEER) database, we screened for patients with stage T1-2N2M0 NSCLC who received surgery from 2010 to 2015. To reduce baseline differences between Non-VPI group and VPI group, two-to-one propensity score matching (PSM) was performed. Cox proportional hazards regression was used to identify factors associated with survival. Overall survival (OS) was between the Non-VPI group and the VPI+ group by the Kaplan-Meier analysis.
We identified 1374 postoperative NSCLC patients with stage pT1-2N2M0. The majority of cases (N = 1047, 76.8%) are Non-VPI patients. The factors associated with VPI+ group included white race (P < 0.0001), and adenocarcinoma (P < 0.0001). When analyzed in the total study population, VPI status remained a significant independent predictor of worse OS compared with the Non-VPI group (HR, 1.343; 95% CI, 1.083-1.665 [P=0.007]). Besides, in a subgroup analysis by VPI status, the results showed that patients without treatment exhibited a higher risk level in the Non-VPI group (P<0.0001). However, we did not find statistically significant differences among treatments in the VPI+ group (P=0.199). Mean survival time was 49.5 months (95% CI: 45.7-53.3 months) for chemotherapy alone in the Non-VPI group, compared with 41.2 months (95% CI: 35.8-46.6 months) in VPI+ groups. In both the VPI group and the non-VPI group, there is no statistical difference between adjuvant chemotherapy combined with PORT and chemotherapy alone.
This study emphasizes that the presence of VPI is a poor prognostic factor, even in patients with Ⅲ/N2 NSCLC. As the study shows, chemotherapy significantly improved overall survival of patients with postoperative stage pT1-2N2M0 NSCLC, especially for Non-VPI patients. However, the significance of PORT is still worth further exploration.

OBJECTIVE: Visceral pleural invasion (VPI) is considered a poor prognostic factor in non-small cell lung cancer (NSCLC). We aimed to analyze the effect of VPI on cancer-specific survival, using propensity score matching (PSM) based on the Surveillance, Epidemiology, and End Results database.
METHODS: We identified 9901 patients with T1-2N0-2M0 who received segmentectomy, lobectomy, or pneumonectomy. Ten covariates were included in PSM. The effect of VPI on survival was assessed, stratified by nodal status and tumor size.
RESULTS: One-thousand and eighty-three pairs of patients were matched with standardized differences of covariates <10% after matching. We found that VPI was associated with a significantly worse survival (3-year survival rate: 84.6% vs. 75.9%, P = 0.005), especially in N0 (P < 0.001), but not in N1 or N2. No significant difference was observed between the extent of VPI. Moreover, VPI conferred a significantly worse survival in tumors >1-2 (P = 0.034) and >2-3 cm (P < 0.001), not ≤1, >3-4, or >4-5 cm in N0.
CONCLUSIONS: VPI is a poor prognostic factor; but with increasing tumor size and nodal stage, its negative effect disappears. Our findings support current staging system which assigns higher T-stage for early >1-2 and >2-3 cm tumors.