Less is More: Video-Assisted Thoracic Surgery (VATS) vs. Open Thoracotomy (OT) in the Management of Resectable Lung Cancer

Lung cancer is the leading cause of cancer-related mortalities around the world [1]. Potentially curable early stage Non-Small-Cell Lung Cancer (NSCLC) can be found in one-third of this patient population [2]. Surgical resection remains the backbone of treatment in resectable lung cancers. The introduction of VATS in 1994 [3] sparked interest in minimally invasive tumor resection. VATS has also been shown to have fewer postoperative complications [4] and has been associated with decreased postoperative pain and increased quality of life compared to OT [5]. Several studies have compared these two approaches indirectly, but no randomized controlled trial has investigated the long-term effect on outcomes. We aim to investigate the long-term Disease-Free Survival (DFS) and OS of patients with lung cancer undergoing lung resection by OT or VATS for resectable stage lung cancer. Patients and Methods


Introduction
Lung cancer is the leading cause of cancer-related mortalities around the world [1].Potentially curable early stage Non-Small-Cell Lung Cancer (NSCLC) can be found in one-third of this patient population [2].Surgical resection remains the backbone of treatment in resectable lung cancers.The introduction of VATS in 1994 [3] sparked interest in minimally invasive tumor resection.VATS has also been shown to have fewer postoperative complications [4] and has been associated with decreased postoperative pain and increased quality of life compared to OT [5].Several studies have compared these two approaches indirectly, but no randomized controlled trial has investigated the long-term effect on outcomes.We aim to investigate the long-term Disease-Free Survival (DFS) and OS of patients with lung cancer undergoing lung resection by OT or VATS for resectable stage lung cancer.

Surgical methods
VATS lung resections were performed via a three-port incision technique including a 4-centimeter anterior axillary working port.The specimens were removed via the working port.Rib spreading was not required.A hilar dissection proceeding from anterior to posterior was performed for lobectomies.For OT resections, a standard posterolateral thoracotomy was used.Generally, bulky tumors, inability to tolerate one-lung ventilation, dense adhesions, en bloc chest wall resections, sleeve resections, neoadjuvant radiation therapy, or intraoperative complications were reasons for selecting an OT approach or for requiring a conversion from VATS to OT.

Study population
Records for patients diagnosed with stage I through III resectable lung cancer treated at Loma Linda University Medical Center from May 2005 through May 2015 were retrieved through a retrospective chart review.Patients were subsequently divided into VATS and OT groups.

Study outcomes
The primary outcome of this study was RFS followed by OS as the secondary outcome.Survival was calculated from the date of surgery to the date of recurrence diagnosis/death or end of study follow-up.

Study covariates
Patient and tumor characteristics included age at diagnosis, sex, tobacco use, tumor location (Side and Lobe), stage, size and type of treatments including chemotherapy or radiotherapy.

Statistical analyses
Tumor and demographic characteristics were compared using Chi-square and Wilcoxon-Mann-Whitney tests.Purposeful variable selection approach was used to identify covariates that were included in the final models.A covariate-adjusted Cox proportional hazards model was used to compare RFS and OS between patients treated with VATS and those treated with OT.Profile likelihood was used to estimate 95% CIs.Proportionality was assessed using Shoenfeld residuals correlations and log-log survival plots.All tests were conducted using R software; R Core Team.R: A language and environment for statistical computing; R Foundation for Statistical Computing, Vienna, Austria.

Recurrence-free survival (RFS) and overall survival (OS)
No significant differences in RFS (Figure 1) (p=0.23) or OS (Figure 2) (p=0.68) were observed between VATS versus OT in the Kaplan-Meier survival curves.After adjusting for covariates, the Cox regression models (Tables 2 and 3), show no difference in RFS, HR=1.26

Discussion
VATS was performed initially in the 1990's.Since then there have been multiple studies advocating the superiority of VATS over conventional OT in terms of short and long-term side effects as well as hospital LOS [18][19][20].However, some surgeons still prefer OT over VATS.In fact, according to the Society of Thoracic Surgeons General Thoracic Surgery Database, the percentage of VATS lobectomies performed in the United States are performed by VATS [21,22] at high volume centers.One explanation for this may be due to the controversial results between several comparative studies in this field [23] since during the resectable years of its development, there was a lack of a clear definition of VATS between thoracic surgeons [24][25][26].The goal of this study was to evaluate the outcomes in a low volume university setting over the last 10-year period, 2005-2015, where VATS was initiated in 2009 (Figure 4).
Our study, like other similar articles (Table 4), did not capture any statistically significant findings between VATS and OT groups in terms of RFS and OS (p=0.23 and p=0.68, respectively).Also similarly, VATS lobectomy was associated with shorter LOS and non-inferior long-term

Procedure
Open

Procedure
Open thoracotomy 1   survival when compared with OT lobectomy.These results support previous findings from smaller single-and multi-institutional studies that suggest that VATS does not compromise oncologic outcomes when used for resectable stage lung cancer [27,28].Over the last 15 years, there have been multiple studies, which have compared VATS to OT (Table 4).As noted in the table, these studies consistently showed decreased LOS and no difference in three to five-year disease free or OS.
Our data is consistent with other data sets retrospectively comparing VATS and OT for resection of resectable non-small cell lung cancer [10,28].
Although our current study did not capture any statistically significant value related to RFS, OS between two surgical modalities but compare to OT, in VATS lobectomy's incisions are smaller with no rib spreading which leads to have a faster recovery.Reviewing the previous studies showed although there was no difference in terms of the timing to receive adjuvant chemotherapy between VATS vs. OT [17] but patients who went under VATS had a better chance to tolerate and complete adjuvant chemotherapy courses, with less need for dose reduction and experiencing less related side effects [29] although still there is lack of data and results about any possible OS benefit [30][31][32].
Our study has several limitations.First and most importantly, our study is a single institution retrospective study.Specific information on patient selection criteria as well as differences in surgeons' experience is lacking and may have led to selection bias.VATS, like all newly developed minimally invasive surgical techniques, requires skills and experience in which not all surgeons have been trained.

Conclusion
Our study suggests that patients undergoing VATS lobectomy in a low-medium sized university setting have comparable long-term and short-term outcomes compared to national data in terms of DFS, OS, and shorter LOSs.This suggests referrals to high volume centers for lobectomy is not required as even low-medium volume centers with board-certified thoracic surgeons trained in VATS can achieve equivalent outcomes.

Figure 3 :
Figure 3: Postoperative length of stay by type of procedure.

Figure 4 :
Figure 4: Forest plot for various treatment subgroups.

Table 4 :
Lobectomy associated with shorter LOS.