Uniportal versus multiportal video-assisted thoracoscopic anatomical resection for NSCLC: a meta-analysis

Since the first pneumonectomy was performed for a patient with non-small cell lung cancer (NSCLC) in 1933, surgery is one of the main treatment methods for NSCLC [1]. The past decades have witnessed continuous evolution and progress of surgical techniques, such as the utilization of segmentectomy and the development of video-assisted thoracoscopic surgery (VATS). Compared with the traditional thoracotomy, VATS has significant advantages, such as lower mortality, reduced postoperative pain, and better quality of life, which have been widely recognized by prospective randomized controlled trials [2‐4]. Conventionally, the traditional VATS, known as multiportal VATS (M-VATS), was performed through 3 or 4 small incisions in the thoracic wall. In recent years, uniportal VATS (U-VATS) has become a new technique in thoracic surgery. Uniportal minimally invasive surgery has developed rapidly since Dr. Rocco first reported in 2004, expanding from the minor thoracic procedures such as wedge resection to complex operations such as lobectomy, segmentectomy, and even bronchial or pulmonary angioplasty [5].

There have already been numerous articles on the feasibility of U-VATS approach in the treatment of lung neoplasm. Quite a few studies showed no difference between the approaches in the key intra- and postoperative outcome [6‐10]. Although some of them have demonstrated several potential advantages of the uniportal VATS technique, such as less intraoperative blood loss, shorter hospital stay, and reduced postoperative pain [11‐13], the results of these studies were highly heterogeneous. For instance, Lin et al. indicated that U-VATS significantly increased operation time compared to M-VATS approach [14], while Bourdages-Pageau et al. held the idea that operation time was significantly decreased in U-VATS group [15]. One study reported shorter average hospital stay with uniportal VATS [16], while another showed it was longer [17]. Comparative clinical outcomes of U-VATS versus M-VATS still remain uncertain.

Here in, we conducted a comprehensive meta-analysis of prospective and retrospective studies, to compare the clinical outcomes of U-VATS and M-VATS anatomical pulmonary resection (lobectomy or segmentectomy) for NSCLC.

This meta-analysis included 20 comparative studies reporting perioperative outcomes between U-VATS and M-VATS in 4142 patients with NSCLC. Compared with previous studies, this meta-analysis, which included the latest studies, has been the largest one on the comparative clinical outcomes between U-VATS and M-VATS anatomical resection for NSCLC so far. Our meta-analysis showed that there was no significant difference between U-VATS and M-VATS in operation time, blood loss, number of resected lymph nodes, conversion rate, drainage duration, length of postoperative stay and pain in POD1.

Recently, several meta-analyses had compared the perioperative outcomes of U-VATS and M-VATS [32‐37]. Some of the previous meta-analyses elucidated better perioperative outcomes on U-VATS. For instance, Yang X.Y. et al. reported that patients in U-VATS group had a significant reduction with regard to blood loss, length of stay, and pain in POD1 compared with patients undergoing M-VATS approach [32]. Yang Z. et al. reported that U-VATS approach significantly reduced length of hospital stay against M-VATS approach [37]. By contrast, our meta-analysis demonstrated that there was no significant difference between U-VATS and M-VATS approach on these results, which showed that U-VATS approach has limited advantage over M-VATS in perioperative outcomes. The difference between this meta-analysis and the previous ones is mainly caused by following reasons. First of all, several previous meta-analyses were not focused on non-small cell lung cancer and included many studies on benign diseases. Compared with surgery for benign diseases, lung cancer surgery requires a radical resection of the primary lesion and lymph node dissection. Therefore, the scope of surgery and the degree of trauma are relatively large. In this situation, the perioperative outcomes of U-VATS may be better. In addition, the present meta-analysis is focused on anatomical pulmonary resection segmentectomy or lobectomy for patients with NSCLC, while some previous meta-analyses included patients undergoing wedge resection.

Both Yang Z. et al. and Yang X.Y. et al. showed that U-VATS achieved a significant reduction in the length of stay. This present analysis adopted length of postoperative stay as the parameter, and demonstrated no significant difference between U-VATS and M-VATS approach. Length of hospital stay includes length of postoperative stay and length of waiting for surgery. The latter depended on preoperative workup process, and could vary a lot according to protocols and criteria in different medical centers and treatment groups. Thus, the utility of length of postoperative stay may avoid potential biases and heterogeneity, and is much more objective reflecting the postoperative recovery.

There have been few studies reporting the long-term outcomes of U-VATS so far. Han et al. demonstrated that there was no significant difference between single-incision group, two-incision group, and three-incision group in both recurrence free survival and overall survival [22]. It is noteworthy that there was a study reporting a significant worse long-term survival in the U-VATS group compared with M-VATS group by Borro et al. in 2016. According to this study, Borro found that U-VATS led to a significant lower survival rate in tumor size (T2) and tumor stage (stage I) for patients with NSCLC by stratifying analysis. Besides that, Borro indicated that U-VATS approach was correlated with a higher risk (HR = 1.78) of death [38]. Due to the lack of studies with regard to long-term outcomes, we are unable to perform a meta-analysis of the long-term results. As surgical oncologists, the major impetus is always focused on optimal oncologic results [39]. A surgical procedure should never be performed by sacrificing the long-term survival. Although it is arbitrary to conclude that U-VATS result in poorer long-term outcomes based on only one study, thoracic surgeons should be cautious to avid uptake of this novel technique without well selecting the appropriate patients with lung cancer. Further studies of the survival of U-VATS are warranted.

VATS techniques are among the major progresses in the history of thoracic surgery beyond all doubt. U-VATS might have some potential advantages over M-VATS in reducing postoperative pain and drainage duration, even though these advantages are not significant. M-VATS, as a standard surgical procedure for NSCLC, has reliable safety and feasibility proved by several large-scale randomized controlled trials [2‐4]. Comparatively, there is still lack of evidence that U-VATS can be less invasive without compromising the long-term survival. Innovation of surgical approach is of great importance, but minimizing the size and number of incisions is only one part of minimally invasive surgery (MIS). We believe that the utilization of MIS should lead to preserving normal organs, prolonging survival, and improving quality of life [40]. For instance, with the help of precise intraoperative frozen section diagnosis of pre-invasive lung adenocarcinoma, we are able to perform sublobar resection for these patients, to spare pulmonary function without impairing the survival [41].

There are some limitations in this meta-analysis. Firstly, U-VATS emerges as a novel surgical technique, so investigators have a propensity to publish positive outcomes to demonstrate the superiority or, at least, feasibility of U-VATS. Consequently, the equivalent results between two approaches reported in this meta-analysis should be quite conservative. Some of our included studies did not control the same surgeon to perform these two procedures, which would bring potential bias to the results of our study [7, 20, 21, 23, 26]. Our meta-analysis showed a high heterogeneity in the comparative outcomes (except conversion rates and number of resected lymph nodes). Several included studies mentioned the learning curve for U-VATS, and it might cause high heterogeneity. Besides, only four included studies are prospective in design, and the majority is retrospective which is of lower quality and inevitably introduce potential biases and heterogeneity to the results. We made a subgroup analysis between PSM&RCT studies and non-PSM studies, and found that the result of PSM studies was consistent with that of all included studies.

To conclude, our results indicate that there is no significant difference in perioperative outcomes between U-VATS and M-VATS approaches in the treatment of NSCLC, which means that U-VATS, up to now, still cannot bring extra benefits over M-VATS on the perioperative recovery of patients. In addition, the differences in long-term outcomes of these two approaches are still unclear. Hence, U-VATS should be prudently chosen in the treatment of NSCLC.