Has the time come to declare video-assisted thoracic surgery lobectomy the standard of care for early stage lung cancer?

In the absence of a well-designed randomized trial, propensity-matched studies are often viewed as the next best level of evidence to guide patient management. Overwhelmingly, published propensity-matched studies from large national databases have all shown the video-assisted thoracic surgery (VATS) approach to be superior to thoracotomy for lobectomy in the surgical treatment of lung cancer. Propensity-matched studies using the Society of Thoracic Surgeons (STS) database (1,2), the American College of Surgeons Oncology Group (ACOSOG) Z0030 study database (3), the American College of Surgeons National Surgical Quality Improvement Program database (4), the Nationwide Inpatient Sample database (5), the surveillance epidemiology and end results (SEER)-medicare database (6), the cancer and leukemia group B (CALGB) 140202 study database (7), the European Society of Thoracic Surgeon database (8), the Premier Prospective Database (9), the French National Database (10), and the National Cancer Data Base (NCDB) (11) have all uniformly shown VATS lobectomy have a lower complication rate and a shorter length of hospital stay when compared with lobectomy by thoracotomy. The current study by Zhao et al. (12) adds to this growing list of published propensity-matched studies that find the VATS approach to be superior.

Zhao et al. (12) compared the VATS approach to muscle sparing thoracotomy for lobectomy in 482 matched patients with clinical stage I lung cancer. The VATS approach was found to have a longer operative time (98.8 vs. 78.0 minutes, P<0.001), fewer lymph node stations sampled (4.3 vs. 5.1, P<0.001), fewer lymph nodes resected (12.6 vs. 17.9, P<0.001), less chest tube days (3.7 vs. 4.8 days, P<0.001), shorter hospital stay (6.0 vs. 7.1 days, P=0.002) and fewer complications (3.3% vs. 9.1%, P=0.008). Operative mortality, recurrence free survival and overall free survival were not different between the two groups. Study weaknesses include the retrospective nature of the data, data from a single institution, the lack of complication grading, and the lack of clarity regarding if the VATS group represented the more recent cohort as the median follow up time for each group was not provided. Despite these limitations, this study by Zhao et al. (12) is consistent with the results from larger propensity-matched studies discussed above, finding advantage with the VATS approach for lobectomy.

Despite all the evidence in favor of VATS, the majority of resections for lung cancer in the USA continue to be performed by thoracotomy. The national rate of lobectomy by VATS is reported at approximately 25%, and even among Thoracic Surgeons, the utilization of the VATS approach for lobectomy remains under 50% as reported by STS database (11). With the preponderance of evidence pointing towards its superiority, it would seem that VATS lobectomy should be deemed the “standard of care” for the surgical treatment of early stage lung cancer. Then why has the adoption of the VATS approach been so slow? The answer lies in the fact that there is currently no well-designed multi-institutional randomized trial to provide us with the high level of evidence necessary to dramatically affected patient care. The need for such a randomized trial stems from the limitations of the current published propensity-matched studies and the concerns regarding nodal retrieval during VATS that seems to surface from time to time in the literature.

It is well known that propensity-matched studies are not substitutes for well-designed randomized trials as such studies can never account for all variables, known and unknown, that can affect the outcome. Although all the published propensity-matched studies, discussed above, effectively account for patient and tumor characteristics during matching, they all fail to account for surgeon characteristics (13). This limitation can significantly affect study results, especially in light of the study by Blasberg et al. (9), where the VATS approach was found to be associated with academic institutions, high volume surgeons and thoracic surgeons after multivariate analysis. VATS surgeons are likely to solely utilize the VATS approach, citing data supporting its superiority; while open surgeons are likely to solely utilize thoracotomy, citing the lack of a randomized studies and also perhaps because of their discomfort with the minimally invasive approach. Therefore even after careful application of propensity-score methods, it remains impossible to distinguish between the surgeon and the approach as they are inextricably intertwined. This limitation, termed inextricable confounding by Blackstone (14), is uniformly seen in all propensity-matched studies that compare VATS versus thoracotomy. By not accounting for surgeon characteristics, it leaves open the possibility that the advantages seen with VATS may be due to surgeon expertise rather than the approach itself, as suggested in an editorial by Wood (15).

With regards to lymph node retrieval during the VATS approach, the data is conflicting. Analysis from the STS database (16), the Danish lung cancer registry (17), meta-analysis by Zhang et al. (18), and even this current study by Zhao et al. (12), have shown that the VATS approach results in a lower number lymph nodes resected and less lymph node stations evaluated as compared to thoracotomy. In contrast, data from the SEER-Medicare database (6) and the NCDB (11) have shown the opposite, with VATS having a higher number of lymph nodes resected; while data from the ACOSOG Z0030 study (3) and the CALGB 140202 study (7) have shown no difference between the two groups with regards to lymph node retrieval. Ultimately, there is no difference between the two groups when long term oncologic endpoints of disease free and overall survival are evaluated, as shown by propensity-matched studies from the SEER-Medicare database (6), the CALGB 140202 study (7), the French National database (10), the Chinese multi-institutional registry (19) and this current study by Zhao et al. (12).

As to the current state of VATS lobectomy, the wide use of this minimally invasive technique continues to be hampered by the limitations of its propensity-matched studies and the continued controversy regarding lymph node retrieval continues. These issues can only be overcome by randomized trial, and we and others have long express the importance of conducting such a trial (6,10,13,15,18,20). If we truly believe that the VATS approach is better for our patients, then as VATS surgeons, we must set aside our bias to conduct a multi-institutional randomized trial. Through randomized trial, we must clearly demonstrate to the medical community its superiority in the important endpoints of complication, mortality, recurrence free survival and overall survival. If this is found to be so, VATS lobectomy should then be deemed the “standard of care” for early stage lung cancer and we should then see a rapid rise in the use this minimally invasive technique.

Acknowledgments

Funding: None.

Footnote

Provenance and Peer Review: This article was commissioned and reviewed by the Section Editor Dr. Qiang Pu (Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, China).

Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/vats.2017.08.04). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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