Accepted Manuscript

Title: Is VATS lobectomy standard of care for operable

non-small cell lung cancer?

Author: Fernando Vannucci Dr. Diego Gonzalez-Rivas

PII: S0169-5002(16)30445-7
DOI: http://dx.doi.org/doi:10.1016/j.lungcan.2016.08.004
Reference: LUNG 5189

To appear in: Lung Cancer

Received date: 7-5-2016

Revised date: 4-8-2016
Accepted date: 10-8-2016

Please cite this article as: Vannucci Fernando, Gonzalez-Rivas Diego.Is VATS
lobectomy standard of care for operable non-small cell lung cancer?.Lung Cancer
http://dx.doi.org/10.1016/j.lungcan.2016.08.004

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Is VATS lobectomy standard of care for
operable Non-Small Cell Lung Cancer?

Fernando Vannucci1,2 and Diego Gonzalez-Rivas3,4,5

1. Department of Thoracic Surgery – Hospital Federal do Andaraí, Rio de

Janeiro/Brazil
2. Department of Thoracic Surgery – Hospital Central da Polícia Militar
(HCPM), Rio de Janeiro/Brazil
3. Department of Thoracic Surgery and Lung Transplant – Coruña University
Hospital, Coruña/Spain
4. Minimally Invasive Thoracic Surgery Unit (UCTMI), Coruña/Spain
5. Department of Thoracic Surgery – Shanghai Pulmonary Hospital, Tongji
University School of Medicine, Shanghai/China

Author’s e-mail addresses:

[email protected]
[email protected]

- Corresponding author: Dr. Fernando Vannucci, MD. – Thoracic Surgery

Department, Hospital Federal do Andaraí – Rio de Janeiro/Brazil
- Address: Rua Leopoldo 280 7th floor – Cirurgia Torácica, Andaraí – Rio de
Janeiro/RJ – Brazil, ZIP code 20541-170.
- Mobile: +55(21) 98162-4110
- Phone/Fax: +55(21) 3518-7572
- E-mail: [email protected]
HIGHLIGHTS
- VATS lobectomy is safe, feasible and cost-effective procedure
- VATS lobectomy offers better post-op quality of life if compared to open
surgery
- Regarding survival, VATS lobectomy equals to open surgery, if not better
- VATS lobectomy should be standard of care in early stage non-small cell lung
cancer
- VATS lobectomy done by skilled surgeons can be an option for more
advanced disease

Abstract
Video-Assisted Thoracic Surgery (VATS) for treatment of lung cancer is being
increasingly applied worldwide in the last few years. Since its introduction, many
publications have been providing strong evidences that this minimally invasive
approach is feasible, safe and oncologically efficient; offering to patients several
advantages over traditional open thoracotomy, particularly for early-stage disease (I
and II). The application of VATS for locally advanced disease treatment has also been
largely described, but probably requires a further level of experience, which is more
likely to be found in reference centers, with skilled experts. Although a large multi-
institutional prospective randomized-controlled trial is the best way to confirm the
superiority of one technique over another, such study comparing VATS versus open
lobectomy for lung cancer is unlikely to ever come out. And in this scenario,
retrospective data remains as the most reliable source of scientific information. Based
on a literature review, the main objective of this article is to discuss to what extent
VATS lobectomy can be considered the gold standard in the surgical treatment of
lung cancer, taking into account the most important comparison aspects between the
minimally invasive approach and open thoracotomy technique. This review addresses
questions regarding lymph node dissection, oncologic efficacy, extended resections
beyond standard lobectomy, post-operative complications / pain / quality of life,
survival rates and the present limits of indication (and contraindication) for VATS, in
order to define the real role of this technique on the surgical treatment of lung cancer
in a minimally invasive, but safe and effective manner.
Keywords: VATS lobectomy; minimally invasive thoracic surgery; lung cancer;
video-assisted thoracic surgery; anatomic lung resection

1. Introduction – Historical note and brief summary of VATS evolution

During the last quarter of century, the surgical treatment of intrathoracic
pathologic conditions has been tremendously changed and influenced by the
appearance and evolution of Video Assisted Thoracic Surgery (VATS) techniques.
Originally, the basic concept of thoracoscopy was first introduced by Hans Christian
Jacobeus, in the end of the 19th century, when he proposed the use of a modified
cystoscope to breakdown pleural adhesions in order to promote therapeutic lung
collapse in patients with tuberculosis [1]. This approach was practically abandoned
after the improvement of the medical treatment for tuberculosis, but after some
decades of forgetfulness, thoracoscopy has re-emerged thanks to technological
advances specially regarding video systems, scopes, cameras, endoscopic staplers and
dedicated surgical instruments, giving birth to what we know as modern VATS.
As in many other areas of surgery, minimally invasive techniques in thoracic
surgery have come to stay, minimizing complications, providing less pain and better
quality of life after surgery, offering faster recovery, better cosmetic results and better
cost-effectiveness, in addition to deliver long term results at least equivalent to those
observed on open surgery, becoming an interesting alternative to treat high risk
patients in a better risk-benefit ratio [2]. And in our opinion, it's reasonable to say that
thoracic surgery has profited more than any other surgical specialty with the advent of
minimally invasive approaches, mainly because of two factors: 1) post-operative pain
has always been historically one of the most inconvenient consequences of open
thoracic surgery, leading to higher risk of post-operative complications and
compromising recovery and post-operative quality of life in a significant number of
patients; 2) the thoracic cavity, with its rigid wall and the ease of handling of deflated
lungs, fits perfectly to video-assisted surgery main principles, usually with no need
for CO2 gas insufflation.
Initially used for diagnostic and simple therapeutic purposes, VATS has became
progressively more accessible and the gaining experience with this method combined
to constant technological evolution permitted its adoption to perform more and more
complex procedures in all fields of thoracic surgery, including the surgical treatment
of patients with operable Non-Small Cell Lung Cancer (NSCLC). This ongoing
evolution also fed the raising of new surgical techniques and approaches for lung
cancer, like uniportal VATS [3], non-intubated VATS surgery [4] and robotic thoracic
surgery as well [5]. Until today, VATS is the cornerstone of all minimally invasive
surgical approaches to the thorax and skilled surgeons using this platform can carry
out practically all kinds of standard and extended lung resections.
Regarding particularly VATS lobectomy for lung cancer, its prompt implement
worldwide has been slower, mostly because of technical and cost-related issues [6, 7].
So, the early experience on VATS lobectomy for lung cancer came from some few
centers of excellence in North America [8, 9, 10], Europe [11, 12] and Asia [13], each
one describing their own technique and results. In the following years, this lack of
standardization regarding the technique might have contributed to slow down the
propagation of VATS lobectomy outside these centers and only within the last decade
more coordinated efforts were made to unify and standardize VATS definitions and
techniques [14,15], regardless the number of incisions/ports used to carry out the
planned lung resection. And so, even more recently, with the increasingly easy access
to the technique (more training programs available, educational activities, prompt
access to internet videos) and the lowering price of the devices needed to perform it,
VATS lobectomy is becoming slowly and progressively widespread worldwide,
including in Latin America [7]. The number of VATS lobectomy cases performed
per year in developing countries seems to be still less than it could be, but we believe
that it tends to change the future, not only thanks to the growing experience with the
technique and wider access to dedicated surgical instruments and disposable stapling
devices, but also due to the implement of reliable database systems in these countries.
According to the published data so far, VATS lobectomy has been already shown
to have many potential advantages over open thoracotomy. A vast number of
publications provide strong evidences that the minimally invasive approach is
oncologically equivalent to open surgery (if not better) [16, 17], with similar (or even
better) survival rates [16, 17]. Medical literature available also provides strong
evidences that VATS lobectomy is also more suitable to high-risk and/or poor lung
function patients [18, 19] and is related to lower complication rates [20, 21, 22], less
post-operative pain [23, 24] and less inflammatory response [23], shorter chest tube
duration and hospital length of stay [20], faster recovery and return to daily activities
[20], better preservation of pulmonary function [23], lower overall cost [22], better
postoperative quality of life [24] and better compliance with adjuvant therapy when
compared to open surgery.
The main objective of this article is to discuss to what extent VATS lobectomy
can be considered the gold standard in the surgical treatment of lung cancer, taking
into account the most important comparison aspects between the minimally invasive
approach and open thoracotomy technique.

2. VATS versus open thoracotomy for lung cancer – Lymph node dissection and
oncological efficacy
The lymph node dissection is an important step on the surgical treatment of lung
cancer. There is no better way to stage the disease accurately and thus, guide further
oncological strategies. Nowadays, there is still an open debate regarding the “quality”
of nodal evaluation provided by VATS when compared to open surgery and its impact
on the oncological outcomes. Some publications [25, 26, 27, 28] indicate a correlation
between the surgical approach and the nodal upstaging likelihood. These articles
indicated a higher lymph node upstaging rate after thoracotomy, independent of tumor
size and extent of resection, suggesting that open surgery could offer a more radical
lymph node dissection, but some interesting findings in each of them should be
individually highlighted, as follows: considering lymph node status as an important
prognostic factor in lung cancer, it is interesting to notice that in one of the studies
[25], even with a lower upstaging rate after VATS surgery, the overall three-year
survival was better in the minimally invasive approach. In another paper [26], the
difference on upstaging rate between the two techniques disappeared when a
subgroup of academic/research programs were analyzed, maybe indicating that lymph
node upstaging ability could be more dependent on surgeon’s experience with VATS
lobectomies and oncological commitment, rather than on the approach itself. In both
papers, propensity matching has minimized the selection bias. In a large multi-
institutional publication [27] evaluating lymph node assessment with VATS or open
surgery in 11,500 anatomic lung resections for lung cancer (including sublobar
resections) found a higher upstaging rate from N0 to N1 in the open group, but the
upstaging rate from N1 to N2 was similar in both groups, suggesting a variability in
the completeness of peribronchial and hilar lymph node evaluation. Another relevant
paper [28], based on the Danish Lung Cancer Registry from 2001 to 2007 (1,513
cases of clinical stage I NSCLC), demonstrated that nodal upstaging occurred in
18.6% of patients and was significantly higher after open surgery for N1 upstaging
(13.1% vs 8.1%; p < 0.001) and N2 upstaging (11.5% vs 3.8%; p < 0.001), but it did
not reflect in worse survival for the VATS group patients: the unadjusted survival was
higher in VATS group and after adjustment by multivariate analysis, there was no
difference between VATS and thoracotomy (hazard ratio, 0.98; 95% confidence
interval, 0.80 to 1.22, p = 0.88). The authors conclude stating that the difference in
nodal upstaging might be result of patient selection for reasons not clarified by the
registry and that VATS is an adequate approach for lobectomy at stage I NSCLC
patients, with no adverse impact on survival when compared to open thoracotomy.
In another retrospective series comparing 1,087 patients surgically treated for lung
cancer in a single institution (610 VATS and 487 open), Berry and coworkers [16]
showed no impairment on oncologic efficacy when VATS was performed. Regarding
the risk of lower upstaging rate on VATS cited by the previously mentioned
publications [25, 26, 27, 28], the author conclude saying that “it must be emphasized
that surgeons performing a VATS lobectomy for lung cancer must accomplish lymph
node removal that is equivalent to what they would accomplish by thoracotomy.
Ultimately, patient outcomes are likely more dependent on whether a surgeon
performs a good oncologic procedure, regardless of the specific approach”.
Irrespective any controversy or open debate about lymph node upstaging, which
indeed seems to occur more frequently after open thoracotomy, several publications
comparing open versus thoracoscopic lymph node dissection accomplish for
equivalence between the two approaches, both in terms of number of lymph nodes
harvested [29] and number of lymph node stations assessed [30].
In accordance to this, some recent publications have suggested that a radical
lymph node dissection can also be achieved through uniportal VATS, regarding
specifically the number of lymph nodes removed and the number of mediastinal
lymph node stations dissected [3, 31, 32, 33].

3. VATS versus open thoracotomy for lung cancer – Extended resections beyond
lobectomy
Historically, VATS lobectomy for lung cancer was initially proposed only for
early stage disease. As the years have passed by and the gaining experience with the
method became significant enough, a few experts started to use the VATS platform to
carry out extended major lung resections, as well.
 Nowadays, some centers and surgeons are known by their capability to perform
not only standard anatomic resections by VATS, but also more complex resections
such as bronchial sleeve, vascular sleeve, carinal, chest wall, and other en-bloc
resections as well. Extended resections, particularly sleeve and carinal resections, are
technically demanding and have a steep learning curve. These procedures must be
done by highly skilled surgeons, with large experience in both VATS lung resections
and open sleeve resections as well.
It is fairly known that minimally invasive pneumonectomies are feasible and have
precise indications in the surgical treatment of lung cancer, but just to keep the focus
on the main objective of this text, this type of resection will not be addressed here.
Sleeve resections are complex operations but they represent an attractive
possibility to avoid pneumonectomy. By reconstructing the airway and/or lobar
arterial blood supply, a significant amount of healthy lung parenchyma is spared.
Therefore, respiratory function is less compromised and also the risk of complications
related to pneumonectomy is avoided. For these reasons, sleeve resections are always
indicated whenever possible, even for patients with normal lung function. It has been
largely demonstrated that sleeve resections are associated with lower morbidity, better
survival and improved quality of life when compared to pneumonectomy [34, 35]. In
the last few years, thanks to recent technological improvements in thoracoscopy and
growing experience with VATS for lung cancer, bronchial sleeve, vascular sleeve and
tracheal/carinal resections are being carried out safely with comparable outcomes to
open approach [36, 37, 38].
When the lung lesion invades the pulmonary artery, a decision must be made: is
possible to avoid a pneumonectomy? And if it is indeed possible, how should the
vascular reconstruction be done? Arterial resections can demand a partial resection
followed by suture (with or without a patch) or it can be necessary to completely
resect an arterial segment, which must be reconstructed by end-to-end anastomosis
(with or without a prosthetic graft). This rationale summarizes the indication and
surgical strategy for a vascular en-bloc resection and reconstruction in lung cancer
cases. VATS approach for vascular sleeve resections and subsequently for double-
sleeve (broncho-vascular) resections are a huge step further in this complex scale of
minimally invasive extended lung resections. The first reports of VATS vascular
sleeve and VATS double sleeve are quite recent [38, 39]. Even though it has been
demonstrated to be technically feasible, double-sleeve and tracheal/carinal resections
still remain as a contraindication for VATS approach in the majority of centers [38].
From a technical point of view, all VATS sleeve resections (including carinal
resections) are very well described and do not differ from those performed by open
surgery [36, 38]. Principles and details regarding how to proceed with vascular
clamping, intravenous heparin use, running suture tips/pitfalls and the unclamping
process are essentially the same that surgeons usually apply on open thoracotomy.
The same can be stated for bronchoplastic procedures. However, Gonzalez-Rivas,
who describes the technique for uniportal VATS sleeve resections, emphasizes that
the availability of bi-articulated VATS dedicated instruments is highly recommended
to ensure more ergonomics, comfort, and safety to the operation [37].
Tumors invading the chest wall and the superior sulcus can also be suitable for
minimally invasive resection in selected patients. Actually, these cases are conducted
by a hybrid approach and VATS has the potential to limit the extent of chest wall
resection and the incision size as much as possible, in addition to avoid rib spreading.
Indeed, using the thoracoscopic view from inside, it is easier to assure exactly where
the tumor invades the chest wall, and therefore precisely define in what extent the
chest wall must be resected. A limited thoracotomy is made exactly over the chest
wall segment to be resected and the invasiveness of the procedure is considerably
reduced. There are some series with few patients that show oncologic outcomes and
survival similar to open surgery [40, 41, 42], with shorter length of stay [40], possibly
leading to less pain and a better recovery of lung function [42].
As just mentioned, almost all resections can be carried out by minimally invasive
means. But is crucial for all thoracic surgeons to keep in mind that extended
resections by VATS are the result of long-term accumulated experience (both in
VATS and in open extended resections). This level of experience and skill is an
indispensable precondition to propose a thoracoscopic approach for a planned
complex major resection. Just like other authors, we believe that these extended
operations should be referred to “high-volume surgeons in high-volume centers with
staged complexity of the procedures being performed” [43].

4. VATS versus open thoracotomy for lung cancer – Crucial post-operative

outcomes: complications, pain, quality of life and survival rates
 VATS lobectomy is a safe procedure and several publications have already shown
that it is related with lower complication rates [20, 44, 45], lower pain and better
quality of life [24] and also at least equivalent survival, if not better [16, 44], when
compared to open surgery.
In a single-institution retrospective series [16], Berry et al. evaluated 1,087
lobectomies and bilobectomies (610 VATS and 477 Thoracotomy) for NSCLC. The
overall 5-year survival rate observed was better in the VATS group (57,5% vs. 43.1%,
p = 0,001). When the authors applied a logistic regression model to calculate
propensity scores using the approach (VATS or open) as outcome, this difference
disappeared (5-year survival was 54,7 for VATS and 48% for open surgery, p = 0,3),
indicating that minimally invasive approach did not have a negative influence on
multivariate survival analysis of this cohort.
In a recent multi center analysis extracted from the previous CALGB 140202
series, the CALGB 31001 study [20] proposed an outcome comparison between
VATS and Thoracotomy for NSCLC in early stage disease (stages I and II). From 350
eligible and matched patients (175 VATS and 175 open), the data retrospectively
collected showed that the mean length of stay was shorter in the VATS group (5.4 vs.
8.0 days, p < 0,0001) and the incidence of any surgical complication was smaller in
this group (14.9% vs. 25.1%, p < 0,0001), as well.
A randomized controlled trial conducted in Denmark recently published [24]
compared VATS Lobectomy and lobectomy by anterolateral thoracotomy for early
stage lung cancer, regarding postoperative pain and quality of life. The final analysis
included 102 VATS and 99 open cases from October 2008 to August 2014.
Postoperative pain was assessed by Numeric Rating Scale (NRS), from 0 (“no pain”)
to 10 (“worst pain imaginable”) and measured six times a day during hospital stay and
then once at 2, 4, 8, 12, 26 and 52 weeks after surgery. Self reported postoperative
quality of life was evaluated using the EuroQol 5 Dimensions (EQ5D) questionnaire
and the European Organization for Research and Treatment of Cancer (EORTC) 30
item questionnaire (QLQ-C30); during hospital stay and at 2, 4, 8, 12, 26 and 52
weeks after discharge. When analyzing pain scores, the results showed a lower
incidence of significant pain (NRS ≥ 3) in the first 24 hours after surgery for VATS
group (VATS 38% vs. Thotacotomy 63%, p = 0,0012) and a lower incidence of
relevant pain episodes (NRS ≥ 3) at the VATS group during the 52 week follow-up
period (p < 0.0001). Regarding quality of life comparison between the two groups, it
was pointed as significantly better after VATs according to EQ5D (p = 0.14), but not
statistically different according to EORTC QLQ-C30 (p = 0,13). Complication rates
were similar between the groups.
A meta-analysis [44] published in 2008 comparing 6370 patients (3114 VATS
cases and 3256 thoracotomy cases) from 39 publications has shown a significant
difference on overall complication rates favoring the VATS group (16.4% vs 31.2%;
p = 0,018), which has had also a better annual survival rate, observed at one, two,
three, four and five years after surgery.
In 2016, a propensity-matched analysis of outcome from the European Society of
Thoracic Surgeons (ESTS) database was published [45] and the results also pointed
towards a statistically significant difference on overall complication rates between the
two approaches, favoring VATS group again (29.1% vs 31.7%; p = 0,0357). Major
cardiopulmonary complications (15.9% vs 19.6%; p = 0,0094), atelectasis requiring
bronchoscopy (2.4% vs 5.5%; p < 0,0001), mechanical ventilation > 48h (0.7% vs
1.4%; p = 0,0075) and wound infection (0.2% vs 0.6%; p = 0,0218) were the
outcomes with statistically significant difference between the two groups. This study
also highlighted that the positive influence of VATS became more evident in high-
risk patients (> 70 years old / poor lung function).
All but one [24] of the above cited publications are retrospective studies and are
not statistically strong as a prospective randomized trial. They must be analyzed
taking into considerations all its strengths and weaknesses, but still represent the best
available source of data, providing reliable evidences, if well and carefully
interpreted.

5. VATS Lobectomy for lung cancer – Indications and contraindications

VATS is a different approach, not a new procedure. Following this rationale, the
preoperative evaluation and indications for surgical treatment remain the same as for
open surgery. Contraindications for VATS have been changing over time since its
introduction, thanks to technological improvements and growing experience with the
platform.
Anyway, when planning a surgical strategy, with respect to indications and
contraindications to VATS in the surgical treatment of lung cancer, all cases actually
must be individualized and analyzed from different perspectives.
 First, from a technical point of view, it seems that the concepts of
indication/contraindication are nowadays more dependent on surgeon’s comfort and
experience. It means that contraindications are usually relative and what could be
considered a contraindication by some surgeons would not necessarily be by another
more experienced and skilled colleagues. Exceptions apply, of course, and huge
tumor masses, mainly when central, tend to be removed by open surgery, regardless
the surgeon’s experience [15]. Situations that were considered contraindications in the
past, such as previous thoracic surgeries or pleural adhesions, today do not
contraindicate a minimally invasive approach, but inability to tolerate single-lung
ventilation still remains a potential contraindication for VATS [46].
From a clinical standpoint, absolute contraindications for open surgery can also be
considered contraindications for VATS (for example: FEV1 < 30% and/or DLCO <
30%), but in the other hand, some selected high-risk patients who are unfit for a
thoracotomy (elderly and/or poor lung function) can be considered surgical candidates
if VATS is an option [15].
Finally, from an oncologic perspective, contraindications when present are usually
absolute, no matter what approach is proposed.

6. Discussion and Conclusion

Definitely, VATS lobectomy can be taught to virtually every thoracic surgeon, but
ideally there must be a standardization of the learning process, just like recently
proposed by Zwischenberger and coworkers [47]. It is also important to consider that
the consensus proposed by the ESTS in 2014 requires a minimum of 50 resections as
a target to achieve technical proficiency in VATS lobectomy and at least 20 cases per
year to maintain operative skills [15]. The main problems to overlap the learning
curve could be pointed out as (1) limited access to disposable devices, specially in
developing countries [7] and (2) limited capacity to expose the learner to a consistent
surgical volume in order to obtain efficient and continuous progress from novice until
proficient level [47]. These issues may preclude or, at least, bring impairments to the
learning process by compromising its initial results. This situation should be taken
into consideration when planning a VATS lobectomy training program.
Perhaps, patients from hospitals that are not initially suitable for a VATS
lobectomy program should be referred to reference centers, or they could be operated
in the same institution, with the aid of a external consultant surgeon who would be
responsible to teach and assist the local team in their first cases, until they can
perform surgeries by their own, in order to avoid complications and ultimately, to
ensure safety.
Regarding the technique itself: four, three or two incisions, uniportal, totally
endoscopic or robotic: it just doesn’t matter! Since the basic criteria proposed by
CALGB 39802 to define VATS are fulfilled [14, 15] and the general oncologic
principles are respected, the best minimally invasive approach is the one that each
surgeon does better and feels more confortable to perform in order to achieve his best
results in a safe manner. So far, there is no proven superiority of one technique over
another.
In the absence of a large multi-institutional prospective randomized-controlled
trial, which is not available – and it seems that is not likely to ever be conducted –
well-collected retrospective data becomes the best source of scientific information.
And so far, most of the published data about this subject provide strong evidences
enough to infer that VATS lobectomy for lung cancer is clearly beneficial for
patients, with better outcomes and oncologic results/survival rates at least equivalent
(if not better) when compared to open surgery, besides all other already mentioned
advantages.
For these reasons, the authors advocate for VATS lobectomy as a feasible, safe,
cost-effective and oncologically appropriate procedure and; in centers where this
technology is available and the surgical team is adequately skilled to perform it
safely, this approach should be considered the standard of care for operable lung
cancer cases. More complex cases and/or those presenting with locally advanced
disease that might be also suitable for VATS resection should be ideally referred to
high-volume reference centers, to be conducted by a team of experts.

Conflict of interest statement: None declared, by both authors.

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