The current meta-analysis demonstrated that the presence of STAS was predictive of significantly worse prognosis in pathological IA stage NSCLC, and patients with STAS experienced obviously poorer RFS, OS and CSS than patients without STAS. However, more prospective randomized controlled trials are still needed to further verify our findings.
To date, the clinical role of the presence of STAS in NSCLC has been identified in several meta-analyses. Pyo et al. included 47 eligible studies and demonstrated that the STAS rate was obviously related to histological subtypes of adenocarcinoma (micropapillary predominant adenocarcinoma: 71.9%, solid predominant adenocarcinoma: 56.7%, papillary predominant adenocarcinoma: 44.6%) [38]. In addition, NSCLC patients with STAS showed a higher incidence rate of visceral pleural, venous and lymphatic invasion, and the presence of STAS was significantly associated with worse RFS (HR = 2.37) and OS (HR = 2.12) [38]. Focusing on early-stage NSCLC, 17 studies involving 9785 cases were enrolled in the meta-analysis by Huang et al., and their results indicated that the presence of STAS was related to poor RFS (HR = 1.93, P < 0.001) and OS (HR = 2.02, P < 0.001) in stage I lung adenocarcinoma [30]. In addition, they conducted subgroup analysis based on the operation mode, and the predictive role of STAS for poor survival was more obvious in patients who received limited resection (RFS: HR = 3.58, P < 0.001; OS: HR = 3.37, P < 0.001) than in patients who received lobectomy (RFS: HR = 1.60, P = 0.019; OS: HR = 1.56, P = 0.061) [30]. However, there are significant differences in therapy strategies between stage IA and IB NSCLC, including the operation mode, adjuvant therapy and proportion of pathological subtypes. Therefore, it is still important to further identify the prognostic role of STAS in pathological IA stage NSCLC.
There are still several issues regarding the clinical significance of STAS in pathological IA stage NSCLC worthy of further investigation. For example, lobectomy and limited resection, including wedge resection and segmentectomy, are all available for IA stage NSCLC. However, whether lobectomy is strongly recommended for patients with STAS remains unclear. In addition, it is believed that some important parameters, including the tumor size, pathological subtype and infiltration degree of adenocarcinoma, may affect the incidence rate of STAS and impact the long-term survival of patients with STAS. Thus, more detailed conclusions should be addressed for specific patient populations in future studies. Furthermore, postoperative adjuvant therapy is not recommended for IA stage NSCLC patients overall. However, we deem that it is still necessary to identify the clinical value of adjuvant therapy for stage IA NSCLC patients with STAS.
There are several limitations in this meta-analysis. First, all included studies were retrospective, and the overall sample size was relatively small. Second, most studies were from Asian countries, including China and Japan, which might limit the generalization of our conclusions. Third, due to the lack of original data, we were unable to conduct more subgroup analyses based on other important parameters, such as tumor size, pathological subtype and type of resection. Thus, more prospective randomized controlled trials are still needed to further verify our findings.