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ORIGINAL ARTICLE
Year : 2016  |  Volume : 12  |  Issue : 2  |  Page : 926-931

Comparison of clinical outcomes after thoracoscopic sublobectomy versus lobectomy for Stage I nonsmall cell lung cancer: A meta-analysis


1 Department of Thoracic Surgery, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China
2 Department of The Third Surgery, Dujiangyan Medical Center, Chengdu 611800, China

Date of Web Publication25-Jul-2016

Correspondence Address:
Jigang Dai
Department of Thoracic Surgery, Xinqiao Hospital, The Third Military Medical University, No. 183 Xinqiao Positive Street, Chongqing 400037
China
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-1482.174181

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 > Abstract 


Background: Although lobectomy has long been considered the standard procedure for Stage I nonsmall cell lung cancer (NSCLC), the selection of sublobectomy for Stage I NSCLC remains controversial. Amidst growing enthusiasm for minimally invasive surgery, the comparison of clinical outcomes after thoracoscopic sublobectomy versus thoracoscopic lobectomy may be of immense value.
Objective: The present study aimed to compare the overall survival (OS) and disease-free survival (DFS) outcomes of patients who underwent thoracoscopic sublobectomy with those who underwent thoracoscopic lobectomy for Stage I NSCLC.
Methods: An electronic search was conducted using five online databases from their dates of inception to February 2014. Hazard ratio (HR) was used in this meta-analysis, calculated from the published survival data.
Results: Eight studies met the selection criteria, including a total of 1613 patients (463 patients underwent thoracoscopic sublobectomy, and 1150 patients underwent thoracoscopic lobectomy). From the available data, compared with thoracoscopic sublobectomy, there was a significant benefit of thoracoscopic lobectomy on OS (HR: 1.45; 95% confidence interval [CI]: 1.11–1.90; P = 0.007). However, in subgroup analysis of thoracoscopic segmentectomy and thoracoscopic lobectomy, there was no significant difference in OS (HR: 1.03; 95% CI: 0.76–1.39; P = 0.85) or DFS (HR: 1.19; 95% CI: 0.67–2.10; P = 0.56) between the two groups. In addition, compared with thoracoscopic wedge resection, there was a significant benefit of thoracoscopic lobectomy on OS (HR: 4.19; 95% CI: 2.19–8.03, P < 0.0001).
Conclusion: For Stage I patients, thoracoscopic segmentectomy leads to survival rates comparable to thoracoscopic lobectomy. However, the overall several of thoracoscopic lobectomy is superior to that of wedge resection.

Keywords: Lobectomy, nonsmall cell lung cancer, segmentectomy, thoracoscopic


How to cite this article:
Liu Q, Wang H, Zhou D, Deng X, Min J, Dai J. Comparison of clinical outcomes after thoracoscopic sublobectomy versus lobectomy for Stage I nonsmall cell lung cancer: A meta-analysis. J Can Res Ther 2016;12:926-31

How to cite this URL:
Liu Q, Wang H, Zhou D, Deng X, Min J, Dai J. Comparison of clinical outcomes after thoracoscopic sublobectomy versus lobectomy for Stage I nonsmall cell lung cancer: A meta-analysis. J Can Res Ther [serial online] 2016 [cited 2019 Dec 12];12:926-31. Available from: http://www.cancerjournal.net/text.asp?2016/12/2/926/174181




 > Introduction Top


Lung cancer is the leading cause of cancer-related mortality worldwide, withabout 1.4 million deaths annually.[1] In 1939, Churchill and Belsey first described pulmonary segmentectomy for the treatment of bronchiectasis, performing lingulectomy in 86 patients.[2] However, since 1995 and the publication of a randomized controlled trial carried out by the lung cancer study group (LCSG), lobectomy with lymph node dissection has been considered the standard surgical treatment for Stage I nonsmall cell lung cancer (NSCLC). The LCSG study found that limited resection for tumors <3 cm in size resulted in inferior overall survival (OS) rates and increased regional recurrence rates compared with lobectomy.[3]

Although that randomized trial (LCSG, 1995) concluded that limited resection should not be the standard procedure even for small, Stage I NSCLC tumors, it continues to be performed. Indeed, results reported from various institutions up to now have been conflicting.[4],[5],[6],[7] However, new developments have renewed interest in sublobectomy for Stage I lung cancer tumors: (1) There is now strong evidence that low-dose computed tomography (CT) screening in high-risk patients reduces lung cancer deaths. (2) Since 1995, newer staging modalities have emerged that will likely improve patient selection for anatomic lung resection, such as combined positron-emission tomography (PET) and PET-CT, transesophageal ultrasonographically guided fine-needle aspiration, and endobronchial ultrasonographically guided transbronchial needle aspiration.[8],[9] (3) Surgeons have advanced the fields of minimally invasive surgical techniques such as video-assisted thoracoscopic surgery (VATS) and are increasing applying those approaches to segmentectomy.[10] In light of these developments, the efficacy of limited resection in Stage I NSCLC needs to be re-evaluated.

Furthermore, there is now a better understanding of the potential advantages of thoracoscopic sublobectomy (i.e., the VATS approach) for anatomic pulmonary resection. When compared to open sublobectomy and lobectomy, the thoracoscopic technique was found to have equivalent oncologic results, with shorter durations of hospital stay, reduced rates of morbidity, and lower costs. A previous review demonstrated that when compared to thoracoscopic lobectomy, thoracoscopic segmentectomy had equivalent rates of morbidity, recurrence, and survival in selected patients.[11] Although several previous meta-analyses have compared clinical outcomes between sublobectomy and lobectomy in an open procedure, the comparison of clinical outcomes after thoracoscopic sublobectomy versus thoracoscopic lobectomy are still unknown.

We conducted a systematic review and meta-analysis of the literature comparing thoracoscopic sublobectomy and thoracoscopic lobectomy methods for Stage I NSCLC and examined the contribution of each method to OS and disease-free survival (DFS). Through t analysis, we hope to reach a consensus about treatment options for clinicians regarding VATS for Stage I NSCLC.


 > Methods Top


Literature search strategy

The rigorous study protocol was established according to the recommendations of the Cochrane Collaboration. Prior to the analysis, in order to ensure the highest quality, we prespecified all of the objectives, inclusion and exclusion criteria, primary and secondary outcomes, and methods of synthesis.

A systematic electronic search was independently performed by two investigators using MEDLINE, EMBASE, and the Cochrane Library Database CENTRAL, from their inception, dates up to February 2014. All articles involving patients with Stage I NSCLC who underwent thoracoscopic sublobectomy or thoracoscopic lobectomy were included in the analysis to achieve the maximum sensitivity of the search strategy and identify all potentially relevant studies. Search terms included “lung cancer,” “NSCLC,” “early stage,” “segmentectomy,” “segmental resection,” “sublobar,” “lobectomy,” and “wedge” and MeSH headings “lung cancer,” “sublobar,” “segmentectomy,” “wedge,” and “lobectomy” were used in combination with the Boolean operators AND or OR.

Selection criteria

Eligible studies included those in which comparative outcomes were presented for patients with Stage I NSCLC, who underwent sublobectomy or lobectomy. The search results were checked by the following inclusion criteria: (1) Operative approaches could have included video-assisted thoracoscopic sublobectomy (segmentectomy or wedge resection) and video-assisted thoracoscopic lobectomy. (2) One of the outcomes of interest was OS/DFS. (3) Articles were peer-reviewed and published as original articles and study subjects had to be limited to clinical Stage I patients. Exclusion criteria included letters to the editor, reviews, and articles published in a book or papers not published in English. When multiple articles by the same author or study group analyzed the same series of patients, the single most informative article was chosen for the meta-analysis.

Statistical analysis

Meta-analysis was performed by combining the results of reported OS and DFS. The log (hazard ratio) (ln [HR]) and its standard error (SE) were used as the outcome measure for data combination. HR and associated variances were obtained or calculated from each selected study using techniques described by Tierney et al.[12] As the HR of OS/DFS could not obtain the data presented in some studies directly, the Kaplan-Meier survival curves in these studies were used to extract the data and to calculate the HR and SE of OS/DFS. Kaplan-Meier curves were read with Engauge Digitizer version 2.11 and calculations were performed independently by two researchers. Discrepancies were discussed to reach consensus. The summary statistical analysis was conducted with Review Manager Version 5.1.2 (Cochrane, http://www.cochrane.org/). Statistical heterogeneity among trials was evaluated using the Higgins I2 statistic to determine the percentage of total variations across studies due to heterogeneity. If the I2 statistic was ≤50%, a fixed-effect model was used to pool studies; otherwise, a random-effects model was used.


 > Results Top


Characteristics of included trials

Eight studies (n = 1613 patients) that met the inclusion criteria were identified; all were performed between 2009 and 2013. The PRISMA diagram was depicted in [Figure 1]. [Table 1] shows details for each trial, including baseline characteristics, study publication year, thoracoscopic surgery method, and tumor stage.[13],[14],[15],[16],[17],[18],[19],[20]
Figure 1: Flow chart of the literature search according to PRISMA statement

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Table 1: Characteristics of included trials

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Primary outcome measures

All eight trials reported the outcomes of OS or DFS following thoracoscopic surgery (thoracoscopic sublobectomy and thoracoscopic lobectomy). When comparing the OS of thoracoscopic sublobectomy and thoracoscopic lobectomy, the combined HR was 1.45 (95% CI: 1.11–1.90; P = 0.007) [Figure 2]. However, in subgroup analysis of thoracoscopic segmentectomy and thoracoscopic lobectomy the combined HR for OS was 1.03 (95% CI: 0.76–1.39; P = 0.85) [Figure 3] and for DFS it was 1.19 (95% CI: 0.67–2.10; P = 0.56) [Figure 4] which indicated that OS and DFS for thoracoscopic segmentectomy were comparable with thoracoscopic lobectomy. In combining the data of another subgroup analysis, OS of patients treated with lobectomy was found to be inferior to patients treated with thoracoscopic wedge resection (HR: 4.19; 95% CI: 2.19–8.03; P < 0.0001) [Figure 5].
Figure 2: Forest plot of comparison: The overall survival of the thoracoscopic sub lobectomy versus thoracoscopic lobectomy for Stage I nonsmall cell lung cancer. Seven studies were included

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Figure 3: Forest plot of comparison: The overall survival of the thoracoscopic segmentectomy versus thoracoscopic lobectomy for Stage I nonsmall cell lung cancer. Seven studies were included

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Figure 4: Forest plot of comparison: The disease-free survival of the thoracoscopic segmentectomy versus thoracoscopic lobectomy for Stage I nonsmall cell lung cancer. Five studies were included

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Figure 5: Forest plot of comparison: The overall survival of the thoracoscopic wedge resection versus thoracoscopic lobectomy for Stage I nonsmall cell lung cancer. Two studies were included

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Funnel plots (for HR or SE [log (HR)]) were drawn for each analysis [Figure 6]. In graphical checks, no asymmetry of the funnel plots could be found. Assessment with the Egger method revealed no evidence of publication bias for any outcomes.[21]
Figure 6: Funnel plots for each comparison. No evidence of publication bias for all outcomes in the Egger test. (a) Funnel plot for comparison (Sublobectomy versus Lobectomy for OS), (b) Funnel plot for comparsion (Secccgmentomy versus Lobectomy for OS), (c) Funnel plot for comparison (Segmentectomy versus Lobectomy for DFS), (d) Funnel plot for comparsion (Wedge resection versus Lobectomy for OS)

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 > Discussion Top


The selection of the appropriate surgical resection procedure for patients with Stage I NSCLC remains controversial; it has been discussed for a number of decades. In a recent retrospective study, Khullar reported that wedge and segmental resections had significantly worse OS rates compared with lobectomy in clinical T1A NSCLC patients.[22] However, their result exists conspicuous limitation for those patients undergoing sublobar resection were more likely to have inadequate lymphadenectomy and positive margins. Although lobectomy is commonly considered the standard approach to achieving long-term oncological efficacy and minimizing the risks of local recurrence, sublobar resections have been shown to preserve lung function without compromising DFS.[23],[24] Since the 1995 LCSG trial, there have been significant advancements in thoracoscopic surgical techniques, including a better understanding of the potential advantages of thoracoscopic lobectomy and segmentectomy for anatomic pulmonary resection.[11] Several studies comparing thoracoscopic surgery with open approach show that thoracoscopic surgery for Stage I NSCLC is both feasible and safe.[25],[26],[27],[28] However, the clinical outcomes of thoracoscopic segmentectomy or wedge resection versus thoracoscopic lobectomy for NSCLC remain unclear. We, therefore, performed a meta-analysis to combine appropriate studies to further examine the published data. Although the meta-analysis was originally developed to combine the results of randomized controlled trials, it has become increasingly common to perform a meta-analysis using observational data.[28],[29] The aim of the present meta-analysis was to compare patients who underwent thoracoscopic sublobectomy with those who underwent thoracoscopic lobectomy. This analytical approach for NSCLC has not previously been performed in the medical literature.

According to our findings, patients who underwent thoracoscopic segmentectomy did not demonstrate any significant differences in OS or DFS compared to patients who underwent thoracoscopic lobectomy. Furthermore, OS was significantly superior in thoracoscopic lobectomy compared with thoracoscopic wedge resection. However, our study had several limitations: (1) The level of evidence was relatively low, with all the studies consisting of level IV evidence and no randomized, controlled trials. (2) We could not collect and analyze data about any chemotherapy or radiotherapy treatments received by any patients in the cohort that might have affected survival rates. (3) In most of the studies included, patients were allocated to the sublobectomy group due to increased comorbidities. In only one included study, sublobar resections (segmentectomies and wedge resections) were also performed on patients who could tolerate a lobectomy. Despite the above limitations, this meta-analysis is the first to compare thoracoscopic sublobectomy (including segmentectomy and wedge resection) with thoracoscopic lobectomy.

Currently, a number of case reports have demonstrated encouraging outcomes for patients undergoing sublobectomy following strict patient selection protocols. In addition, two clinical trials are currently focused on the topic: The Japan Clinical Oncology Group with the West Japan Oncology Group launched a phase III randomized trial (JCOG0802/WJOG4607L) in 2009, and the National Cancer Institute launched a randomized phase III trial (CALGB 140503) in 2008. Those two ongoing randomized trials will clarify the role of thoracoscopic sublobectomy in Stage I NSCLC.


 > Conclusion Top


The current meta-analysis disclosed two main results: (1) OS and DFS following thoracoscopic segmentectomy for Stage I NSCLC are comparable to those following thoracoscopic lobectomy, and (2) thoracoscopic lobectomy produces significantly superior OS compared to thoracoscopic wedge resection for patients with Stage I tumors. Considering heterogeneity among studies and most data were from retrospective studies, the results of the meta-analysis should be interpreted with caution.

Acknowledgments

The authors would like to thank the study participants for their contribution to the research, as well as current and past researchers and staff. The study was supported by the funding from the General Program of National Natural Science Foundation of China (81172238, 81472188). The work was supported by the Third Military Medical University.[30]

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
 > References Top

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