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Eur J Cardiothorac Surg 2002;21:1094-1099
© 2002 Elsevier Science NL

VATS is an adequate oncological operation for stage I non-small cell lung cancer

^a Department of Thoracic Surgery, Sainte Marguerite Hospital-CHU Sud, Université Méditerranée (Aix-Marseille II), School of Medicine, 270 Bd Sainte Marguerite, 13274 Marseille, France
^b UPRES EA 2201, IFR Jean Roche, France
^c Department of Medical Information and Biostatistics, Sainte Marguerite Hospital, Université Méditerranée (Aix-Marseille II), School of Medicine, 13274 Marseille, France

Received 14 September 2001; received in revised form 8 January 2002; accepted 15 March 2002.

* Corresponding author. Tel.: +33-491-744-680; fax: +33-491-744-590
e-mail: pathomas{at}ap-hm.fr

	Abstract

Top Abstract 1. Introduction 2. Materials and methods 3. Results 4. Discussion Appendix A. Conference... References

 
Objectives: This study was designed to determine the long-term prognosis of video-assisted thoracic surgery (VATS) vs. open lung resections for patients with pathological stage I non-small cell lung cancer (NSCLC). Materials and methods: The medical records of all patients who underwent lung resection for a pathological stage I NSCLC were reviewed for the period from 1990 to 1999, by screening of a database into which data were entered prospectively. There were 511 patients (430 males and 81 females) whose age averaged 63±10 years who underwent 515 lung resections. Our VATS experience began in 1993 with selected stage I patients, and since that date an average of one patient on four was managed with VATS. Lung resections consisted of 25 wedge resections or segmentectomies (seven VATS), 390 lobectomies (92 VATS), 19 bilobectomies (one VATS) and 81 pneumonectomies (ten VATS). Lymph node dissection was performed in all cases. Results: There were significantly more females (P=0.01) and adenocarcinoma (P=0.02) in the VATS group (n=110) when compared to the open group (n=405). Tumour size averaged 4±2 cm in the open group and 3±2 cm in the VATS group (P=0.04). The distribution of T1/T2 tumours was 97/308 and 50/60, respectively (P=0.0001). At follow-up, cancer recurrence could be documented in 117 patients, with no difference of incidence between the two groups (22.5 vs. 24.5%; P=0.64). Estimated Kaplan–Meier 5-year survival rates, including the operative mortality as well as any cancer-related and unrelated death, were 62.8% (confidence interval (CI): 56.8–68.7%) vs. 62.9% (CI: 51.4–74.4%), respectively (P=0.60). The advent of VATS did not influence the patients' survival: 5-year survival rate was 63.9% (CI: 55.3–72.5%) for the period from 1990 to 1992, and 58.8% (CI: 51.7–65.9%) for the period from 1993 to 1999 (P=0.65). Subgroups survival analysis according to the T status did not show any statistically significant difference between the two groups. Conclusions: VATS lung resection with lymph node dissection achieved a 5-year survival similar to that achieved by the conventional approach. VATS is a valuable option for the management of selected patients with an early-stage NSCLC.

Key Words: Video-assisted thoracic surgery • Non-small cell lung cancer

	1. Introduction

Top Abstract 1. Introduction 2. Materials and methods 3. Results 4. Discussion Appendix A. Conference... References

 
The adequacy of video-assisted thoracic surgery (VATS) as a cancer operation is still controversial. Regarding the treatment of non-small cell lung cancer (NSCLC), however, there is some ground suggesting equivalent survival following either VATS and thoracotomy. Any meta-analysis of the literature, however, is hampered by the absence of large prospective comparative studies, the wide variety of minimally invasive techniques used and the remaining uncertainty about optimal patients selection. From the beginning of our experience in 1993 with VATS for major lung resections for NSCLC, we adopted a very pragmatic policy. First, a VATS approach was proposed only to a small subset of patients, mainly those having a small stage I tumour and demonstrating no technical and/or anatomical difficulties. Second, our technique included a minithoracotomy and a rib spreader to facilitate the operation. Having assessed the feasibility of our technique [1], identifying its possible benefits at short- and middle-term evaluation [2], the purpose of the present study was to report on the long-term survival on the basis of prospectively gathered data. We limited our study to those patients who were proved to have a pathological stage I disease, because it is in this homogeneous group of patients with a relatively favourable oncological prognosis that one can confront best the impact of other factors.

	2. Materials and methods

Top Abstract 1. Introduction 2. Materials and methods 3. Results 4. Discussion Appendix A. Conference... References

 
The medical records of all patients who underwent lung resection for a pathological stage I non-small cell lung cancer, as defined by the new International Classification System [3], were reviewed for the 10-year period ranging from January 1990 to December 1999. Patient charts were identified by screening of a database into which data were entered prospectively for any patient undergoing surgery for lung malignancy at our department.

There were 511 patients, 430 males and 81 females, whose ages ranged from 31 to 86 years (mean: 63±10 years). These 511 patients underwent 515 lung resections; four patients having undergone a second operation for a metachronous NSCLC during the study period.

An open approach was performed in 405 patients through a posterolateral thoracotomy (n=295), or a muscle-sparing lateral thoracotomy (n=109). Anecdotally, a sternotomy was used in one patient who required the combined resection of a contralateral giant bulla.

Our experience with VATS began in February 1993 with selected patients fulfilling the following criteria: clinical stage I disease, tumour size less than 5 cm, no dense pleural adhesions at thoracoscopic exploration, near complete fissure and free hilum. VATS was performed in 110 patients. The technique was already described elsewhere [1]. Briefly, the procedure begins with the video-thoracoscopic inspection of the pleural cavity through a 10-mm port access inserted in the anterior aspect of the sixth intercostal space. A 5-cm utility thoracotomy is then performed on the midaxillary line in the fifth intercostal space, and can be converted at any time in a lateral thoracotomy. Access to the chest is widened by the use of a specific rib spreader. One 12-mm supplementary port is usually inserted in the posterior aspect of the seventh intercostal space. The two trocarts are used indifferently for the video-thoracoscope and endoscopic linear cutting stapplers required for the division of the posterior part of the oblique fissure and/or the pulmonary vessels. The operating surgeon divides the pulmonary vessels and bronchus separately under direct vision through the minithoracotomy, while an assistant surgeon assists through the other ports, using the TV monitor for guidance. Mediastinal lymph node dissection is usually performed under TV monitor guidance. It includes the resection of all nodes in stations 10 and 11, and at least the sampling of the following node stations: 7 and 9 in all cases, 2R and 4R in right-sided resections, 4L, 5 and 6 in left-sided resections. Frozen sections are performed in any suspicious node, and the procedure is converted to an open one whenever a N+ disease is disclosed in order to perform a radical lymphadenectomy. The operative specimen is removed in a surgical bag. Specific surgical instrumentation, but mainly standard staplers and stitches are used.

Lung resections consisted of 25 wedge resections or segmentectomies (seven VATS), 390 lobectomies (92 VATS), 19 bilobectomies (one VATS) and 81 pneumonectomies (ten VATS). Complete R0 cancer resection was achieved in all patients.

Pathology disclosed an adenocarcinoma in 216 cases, a squamous cell carcinoma in 215 and a large cell carcinoma in 72. Miscellaneous non-small cell types were found in 12 cases. There were 147 stage IA tumours, and 348 stage IB tumours. The tumour size ranged from 0.5 to 13 cm (mean: 4±2 cm). Blood vessel invasion was identified on 34 surgical specimens. Table 1 details the characteristics of the patients with respect of the surgical approach. The proportions of female and adenocarcinoma were significantly higher in the VATS group. Tumours were also smaller in size and the T status differed consequently with a majority of T1 tumours in the VATS group. In turn, the incidence of pneumonectomy was lower in the VATS group.

	3. Results

Top Abstract 1. Introduction 2. Materials and methods 3. Results 4. Discussion Appendix A. Conference... References

 
Fig. 1 illustrates the number of patients operated on during the study period with respect to the surgical approach. Fifteen patients died of the operation (2.9%). The operative mortality rates were 2.7% in the VATS group (n=3), and 3% in the open approach group (n=12; P=0.85). Estimated overall survival rates were 61.1% (55.8–66.5) and 44.2% (36.9–51.5) at 5 and 10 years, respectively.

View larger version (17K): [in this window] [in a new window]   Fig. 1. Number of procedures performed per year according to the surgical approach.

The advent of VATS did not influence the patients' survival: 5-year survival rate was 63.9% (CI: 55.3–72.5%) for the period from 1990 to 1992, and 58.8% (CI: 51.7–65.9%) for the period from 1993 to 1999 (P=0.65). Overall 5-year survival rates associated with VATS and open procedures (Fig. 2 ) were 62.9% (CI: 51.4–74.4%) and 62.8% (CI: 56.8–68.7%), respectively (P=0.60). Overall 5-year survival rates in stage IA patients (Fig. 3 ) were 64.9% (CI: 47.3–82.5%) in the VATS group and 79.7% (CI: 69.6–89.9%) in the other group but this difference did not reach statistical significance (P=0.15). In stage IB patients (Fig. 4 ), 5-year survival rates were 61.2% (CI: 45.9–76.5%) and 58.1% (CI: 51.2–65%), respectively (P=0.40).

View larger version (24K): [in this window] [in a new window]   Fig. 2. Survival curves with respect to the surgical approach.

View larger version (20K): [in this window] [in a new window]   Fig. 3. Survival in stage IA patients according to the surgical approach.

View larger version (22K): [in this window] [in a new window]   Fig. 4. Survival in stage IB patients according to the surgical approach.

	4. Discussion

Top Abstract 1. Introduction 2. Materials and methods 3. Results 4. Discussion Appendix A. Conference... References

Port site tumour recurrence is a reported complication of VATS [4], but our experience illustrates that its true incidence may be low when meticulous technique for the extraction of specimens in dedicated plastic bags is used. Furthermore, we never hesitated to convert the operation to a formal thoracotomy whenever a technical difficulty was encountered in connection with local anatomical or tumoral conditions, which avoided excessive manipulations and inherent risks of spreading. Yamashita et al. [5] prospectively tested whether circulating tumour cells could be found perioperatively in the peripheral blood of patients with pathological stage I NSCLC who underwent video-assisted lobectomy, and compared their data to those of a historical group of patients operated on through a conventional approach. The occurrence of circulating tumour cells during video-assisted lobectomy was significantly higher than in patients who underwent open lobectomy (89 vs. 51%), suggesting that VATS, as compared with open surgery, may increase the risk of seeding tumour cells into the circulation during operation.

Conversely, it was suggested recently that the degree of procedural invasiveness may influence the extent of immunosuppression. In randomised patients undergoing lobectomy for NSCLC, the team of Edinburgh [6] demonstrated that VATS, when compared with thoracotomy, was associated with less traumatic insult to the patient, and consequently, reduced the activity of the acute phase cytokine IL-6 and mediators (C-reactive protein, reactive oxygen species) and effector cells of cellular immunity. The same team [7] had previously reported that VATS was also associated with less effect on specific anti-tumour immunity (CD4 T-cells and natural killer cells) and non-specific secondary immunity (phagocyte responses). These findings could suggest a better maintenance of host immune competence against cancer following resection by VATS when compared with open surgery.

However, true endpoints are overall survival and incidence of cancer recurrence, assessed best by comparison with the standard treatment in randomised patients. One should notice that about 10 years after the advent of this method, there is still hardly any data from so-designed studies. Nevertheless, our data seem to agree with those from the literature [8–13] (Table 2). First, there does not seem to be an excess of cancer recurrences such as would be expected with inadequate local resection. Second, reported survival data indicate that the results with Stage I NSCLC are similar to those reported following equivalently staged conventional resection. Longer follow-up, however, is required given the wide variety of reported figures, some of which seem to be exceptionally good. Randomised studies are still required to confirm or to moderate some enthusiastic claims on a possible superiority of VATS over thoracotomy [10].

We conclude that VATS lobectomy could be accepted as a valuable surgical option in the treatment of highly selected patients with early-stage lung cancer given that it provides similar overall survival and incidence of cancer recurrence than the standard approach. PET-scanning will probably help to better define in a near future the place of VATS in the therapeutic oncological armamentarium. To date, a substantial improvement having been demonstrated in terms of early postoperative course, this minimally invasive approach should be applied preferentially in aged or frail patients.

	Footnotes

 
Presented at the joint 15th Annual Meeting of the European Association for Cardio-thoracic Surgery and the 9th Annual Meeting of the European Society of Thoracic Surgeons, Lisbon, Portugal, September 16–19, 2001.

	Appendix A. Conference discussion

Top Abstract 1. Introduction 2. Materials and methods 3. Results 4. Discussion Appendix A. Conference... References

 
Dr H. Toomes (Stuttgart, Germany): I want to ask you about the converting rate, you didn't say about that, and the operating time, and the criteria for your converting rate.

Dr Thomas: The converting rate has evolved along the study period. At the beginning of our experience, the converting rate was about 8%, as published in our first report in the European Journal of Cardiothoracic Surgery. With time and with the necessity that this kind of surgery remains compatible with the overall scheduled surgical activity, the rate of conversion raised paradoxically and is about 25%. Indeed, we now convert as soon as possible in order to avoid long operative times whenever any anatomical or technical difficulty is encountered. As a consequence, we can state that the operative time in the VATS group is similar to that of the open group.

Dr T. Orlowski (Warsaw, Poland): First of all, I would like to ask you, what was the reason of pneumonectomy in stage I disease, and second, let's say, it was not the real video thoracoscopy, it was, rather, a mini thoracotomy with video-assisted surgery, but did you do any kind of lymph node exploration?

Dr Thomas: When looking at the literature, one may notice that as high as 20% of all surgical procedures performed for a stage I NSCLC may be pneumonectomies. In our series, the ten patients who received VATS pneumonectomy had proximally located tumours. Undoubtedly, some of them would have been suitable candidates for a bronchial sleeve lobectomy. However, our policy at that time was to perform a pneumonectomy whenever the lung function allowed this kind of resection. Now, our policy has a little bit changed and we favour a bronchial sleeve resection whenever it allows a complete resection.

Dr Orlowski: Some of the authors indicated that the appropriate indications for video-assisted lobectomy is a tumour which is situated very favourably.

Dr Thomas: Yes.

Dr Orlowski: So don't you think that in those particular cases you will be able to do, for example, a sleeve or even a simple lobectomy if you do it with the open technique?

Dr Thomas: I do agree with you. Some patients with a proximally located tumour are now advantageously managed with a bronchial sleeve lobectomy. In our opinion, this is not possible to date with a VATS approach.

We also agree with you with the fact that this technique is rather a video-assisted mini thoracotomy than video-thoracoscopy. We always used these terms in our previously published reports.

When one analyses in detail the data of the literature, one notices that the length of the utility thoracotomy incision lengthen with time, and that most teams now use a retractor and sometimes a costal section at the time of the extraction of the operative specimen. We perform this minithoracotomy from the beginning of the intervention, and optimise it with a retractor. This facilitates dramatically the operation and allows the performance of the lymph node dissection in similar conditions to those offered by an open thoracotomy.

Dr P. Van Schil (Antwerp, Belgium): As I stated yesterday during the postgraduate program, there are no good studies looking at the cost analysis of a VATS lobectomy or pneumonectomy compared to a traditional open thoracotomy. As you seem to have a very large experience in VATS surgery, did you look at the cost analysis of a VATS lobectomy vs. a traditional open thoracotomy? I realise it is not a randomised study, but do you have any idea about the cost issue?

Dr Thomas: No, we have not looked at this end point. In France, it is very difficult to appreciate real costs due to the treatment, because an all-inclusive price per day of hospitalisation is used.

Mr K. Moghissi (East Yorkshire, UK): I have a question which is based really on the results that you very well illustrated, that for one group of patients in stage I, a thoracotomy gives better results, okay? Now, at what stage do you decide that particular subgroup should have a thoracotomy and not VATS? I can't see how you can distinguish that at the start. Can you do that?

Dr Thomas: On the basis of a retrospective study it is always difficult to assess.

Mr Moghissi: You see, you have got a patient, I mean with respect to that here it is, he has got a tumour, stage I. Am I agreeing to do a thoracotomy or VATS? How do I decide?

Dr Thomas: Well, a difficult question! In some patients another reason may be taken into account. In an older patient, a patient with an impaired lung function, or with other substantial co-morbidity, we trust that this technique offers a better early recovery. When looking at the oncological efficacy, I have to emphasise that thoracotomy remains our standard approach.

Mr R. Berrisford (Exeter, UK): You showed us that the VATS group had a higher proportion of T1 tumours and that the mean tumour size in the VATS group was smaller. Were you disappointed that the survival was exactly the same in the two groups? Is there a worry that the patients in the VATS group, maybe because they were operated on thoracoscopically, had an equal, not better outcome than the open group?

Dr Thomas: The main explanation is sampling probably. Indeed, if stage IA patients had a worse survival in the VATS group, stage IB patients had a better survival than patients of the open group. When looking at the interval of confidence, there is a very wide range for the VATS survival curve.

Moreover, in the previous presentation from Poland, you could notice that stage I NSCLC patients had a 50% survival at 5 years. Our 62% rate, whatever the surgical approach used, compares favourably. We all know when looking at the literature that there is a very wide range of 5-year survival for stage I disease, and this feature is a major matter of concern. When you look at some Japanese studies with a 90% survival rate at 5 years, it is still a lot better than 60%.

Dr D. Branscheid (Grosshansdorf, Germany): What was the reason of death for those patients who you lost during that period?

Dr Thomas: The incidence of cancer recurrence was the same in the two groups: 24% in the VATS group and 22% in the open group developed cancer recurrence, and because of this, the two groups were similar.

Dr Branscheid: Local recurrence or spread metastases –

Dr Thomas: Both.

Dr Branscheid: – or recurrence in the mediastinum of lymph nodes? Did you differentiate that?

Dr Thomas: No, it was impossible because of the small sampling, but the cause, local or distant metastases, was not different between the two groups.

	References

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