Does Thoracoscopic Pneumonectomy for Lung Cancer Affect Survival?

Does Thoracoscopic Pneumonectomy for Lung Cancer Affect Survival?

Does Thoracoscopic Pneumonectomy for Lung Cancer Affect Survival? Chukwumere E. Nwogu, MD, Sai Yendamuri, MD, and Todd L. Demmy, MD Department of Thor...

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Does Thoracoscopic Pneumonectomy for Lung Cancer Affect Survival? Chukwumere E. Nwogu, MD, Sai Yendamuri, MD, and Todd L. Demmy, MD Department of Thoracic Surgery, Roswell Park Cancer Institute and University at Buffalo, Buffalo, New York

Background. Although thoracoscopic pneumonectomy may be performed safely, its effect on survival is unknown. Methods. Seventy patients underwent elective pneumonectomy for malignancy at a comprehensive cancer center (Roswell Park Cancer Institute, Buffalo, NY) from 2002 to 2008. Using the same incision set as thoracoscopic lobectomy, candidates for a thoracoscopic pneumonectomy had adequate hilar visualization using flexible thoracoscopy, tissue control using novel retractors, and intrapericardial exposure when appropriate. The bronchus was divided last to prevent excessive traction on the main pulmonary artery. Results. Thirty-four percent of patients had neoadjuvant therapy, proportionally distributed among groups. Patients in the thoracoscopic group had shorter lengths of stay in the hospital and less operative blood loss. Eight patients who were converted to thoracotomy had signif-

icantly more operative blood loss. The complication rates were similar among thoracoscopic, converted, and open groups. For both the thoracoscopic and open groups there was 1 death before 30 days. Between 30 and 90 days there was 1 death in the thoracoscopic group as a result of disease progression and 2 deaths in the open group as a result of cardiovascular causes. There was a modest improvement in overall survival in the video-assisted thoracic surgery group relative to the thoracotomy group, but the former group had smaller tumors. When stratified by stage, there was no survival difference. Conclusions. Pneumonectomy performed either by means of thoracoscopy or thoracotomy resulted in equivalent survival. Further studies and follow-up are needed to verify the benefits of video-assisted thoracic surgery pneumonectomy for lung cancer. (Ann Thorac Surg 2010;89:S2102– 6) © 2010 by The Society of Thoracic Surgeons

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racoscopic pneumonectomy (TP) performed for lung cancer at a comprehensive cancer center.

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horacoscopic procedures are expanding in their popularity and application to more complex operations. Multiple studies have demonstrated the benefits of thoracoscopic lobectomy [1– 4]. These benefits have included shorter hospital stay, decreased pain, decreased blood loss, earlier return to normal activities, better tolerance of adjuvant chemotherapy, and improved quality of life. Oncologic equivalence between thoracoscopic and open lobectomy has been reported, and some studies have even suggested superior survival after video-assisted thoracic surgery (VATS) lobectomy compared with open resections [1, 5]. Immunologic mechanisms may account for this putative improved survival [6, 7]. The application of minimally invasive techniques to larger resections such as pneumonectomy and chest wall or sleeve resections has been limited owing to concerns about safety, technical feasibility, and oncologic equivalence to conventional, open resections. However, there is a growing body of literature that suggests that more radical pulmonary resections can be safely accomplished by use of minimally invasive incisions [8 –13]. This retrospective review was undertaken to compare the short-term to midterm survival of patients undergoing open and tho-

Material and Methods After obtaining approval from our institutional review board, a retrospective review of the records of patients undergoing pneumonectomy for lung cancer between January 1, 2002, and September 30, 2008, was performed. Indications for pneumonectomy were hilar lesions not amenable to sleeve resection or synchronous, central, ipsilateral upper and lower lobe malignancies. Patients requiring emergent pneumonectomy were excluded. Pre-resection workup included pulmonary function testing, computed tomography, positron emission tomography, and mediastinoscopy. Thoracoscopic pneumonectomy was performed using two 12-mm access ports and a 4- to 5-cm access incision without rib spreading. Our technique of TP has been described in detail previously [12]. Pericardia were opened selectively to accomplish safe division of the proximal pulmonary vessels, and bronchi were always divided last to prevent excessive traction on the main pulmonary artery. All patients who received radiation therapy had some form of buttressing

Presented at the 2nd International Bi-Annual Minimally Invasive Thoracic Surgery Summit, Boston, MA, October 9 –10, 2009. Address correspondence to Dr Nwogu, Department of Thoracic Surgery, Roswell Park Cancer Institute, Elm and Carlton Sts, Buffalo, NY 14263; e-mail: [email protected].

© 2010 by The Society of Thoracic Surgeons Published by Elsevier Inc

Drs Nwogu, Yendamuri, and Demmy have no conflicts of interest to disclose.

0003-4975/$36.00 doi:10.1016/j.athoracsur.2010.03.019

of the bronchial stump performed (intercostal muscle, parietal pleura, or pericardial fat pad). Preliminary thoracoscopic evaluation was performed routinely in all cases, including planned open resections. Conversions were defined as operations during which dissection for a TP had begun and a thoracotomy with rib retraction had to be subsequently performed. Data on perioperative outcomes including length of stay (LOS), intensive care unit (ICU) days, complications, blood loss, length of operation, and time to start adjuvant chemotherapy were obtained. Complications studied included arrhythmias, need for blood transfusions, pneumonia, myocardial infarction, bronchopleural fistula, and death. Pneumonia was defined as any clinical symptoms (productive cough) or infiltrate on radiograph requiring any duration of antibiotics. Descriptive statistics such as frequencies and relative frequencies were computed for categorical variables. Numeric variables were summarized using simple descriptive statistics such as the mean, standard deviation, range, and so forth. They are represented in the tables by their median values. Fisher’s exact test was used to study the association between categorical variables. The Wilcoxon rank sum test was used to compare the groups in regard to numeric variables. A nominal significance level of 0.05 was used in all testing. All statistical analyses were done using SAS (version 9.1; SAS Institute, Cary, NC) and GraphPad Prism (version 5.2; GraphPad Software, Inc, La Jolla, CA).

Results Seventy patients had pneumonectomies at our institution. Three patients requiring emergent pneumonectomies were excluded (1 for bleeding after a mediastinoscopy, 1 for pulmonary arterial bleeding during a thoracoscopic lobectomy, and 1 for massive hemoptysis). Of the 67 patients included in the final analysis, 32 were initially attempted by thoracoscopy. Eight patients Table 1. Patient Demographics Characteristic Sex, n (%) Male Female Age (y) Comorbidities n (%) Coronary artery disease Diabetes Hypertension PFTs FEV1 Dlco a

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Thoracoscopic (n ⫽ 24)

Open (n ⫽ 35)

Conversion (n ⫽ 8)

9 (38)a 15 (63)a 67

25 (71) 10 (29) 62

4 (50) 4 (50) 62

3 (13)

6 (17)

1 (13)

2 (8) 11 (46)

1 (3) 17 (49)

1 (13) 2 (25)

87 75

77 69

87 65

p ⬍ 0.05 thoracoscopic vs open.

Dlco ⫽ diffusing capacity of the lung for carbon monoxide; FEV1 ⫽ forced expiratory volume in 1 second; PFTs ⫽ pulmonary function tests.

Table 2. Perioperative Data Variable

Thoracoscopic Open Conversions (n ⫽ 24) (n ⫽ 35) (n ⫽ 8)

Operative data EBL (mL) Time (min) Length of stay (days) ICU Hospital Neoadjuvant treatment n (%) Chemotherapy alone Chemotherapy and radiation Adjuvant treatment Patients (%) Time to start (days) Stage (7th ed) n, (%)a I II III IV a

200a 272a

600b 340b

1 4.5a

2 6

3.5b 8

7 (29) 1 (4)

7 (20) 6 (17)

1 (13) 1 (13)

58 52

46 60

5 (22) 14 (61) 4 (17) 0

p ⬍ 0.05 thoracoscopic vs open.

EBL ⫽ estimated blood loss;

300 228

b

5 (15) 10 (29) 18 (53) 1 (3)

63 64 1 (14) 4 (57) 2 (29) 0

p ⬍ 0.05 conversions vs open.

ICU ⫽ intensive care unit.

(25%) were converted from TP to thoracotomy. The reason for conversion was tumor extension in 5 patients and bleeding in 1 patient. Inability to safely dissect the proximal pulmonary vessels owing to peritumoral scarring or very thick adhesions between the tumor and the hilar structures led to conversions in the remaining 2 patients. This resulted in a total of 24 patients in the TP group, 35 patients in the open group, and 8 patients in the conversion group. Demographic information on these three groups is provided in Table 1. There were more female patients in the TP group compared with the open group, but there were no other significant differences among the groups. Twenty-three patients (34%) had neoadjuvant therapy, proportionally distributed among groups. The mean tumor size was 3.8 cm in the TP group, 4.5 cm in the open group, and 3.0 cm in the converted group. There were more stage III patients in the open group (Table 2). Histologic types of cancer were not significantly different among the groups. There was also similar lymph node sampling among groups, reflected by similar numbers of lymph nodes harvested and lymph node positivity rates. Perioperative data are shown in Table 2. Compared with the open group, blood loss was significantly less in the TP group whereas operative time was increased. In the patients requiring conversion to thoracotomy, both blood loss and operative time were increased compared with the open group. There were no significant differences in the need for blood transfusion among groups. There was a shorter hospital length of stay in the TP group compared with the open group (Table 2). How-

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ever, the conversion group had a significantly longer intensive care unit stay compared with the open group. Complications, both noninfectious and infectious, were similar among all three groups. An intention-to-treat analysis was done, and the complication rates still remained similar in the two groups (Table 3). There were 2 perioperative deaths. One patient who had an open procedure died of acute respiratory distress syndrome in the setting of a bronchopleural fistula on postoperative day 24. The other death occurred on postoperative day 13 in a patient undergoing a TP and was attributed to pneumonia and respiratory failure. There were 3 deaths occurring between 30 and 90 days. One thoracoscopic patient was readmitted from home with rapid disease progression in the liver and died on postoperative day 76. Two open patients died, 1 on day 41 as a result of a stroke in a rehabilitation facility and another on day 66 at home of probable myocardial infarction. The median follow-up of the patients in our series is 47 months. Using an intent-to-treat analysis (conversions included in the thoracoscopic group), for stages I to III non–small cell lung cancer, the median overall survival was 51 months for the thoracoscopic cases compared with 23 months for the open cases (p ⫽ 0.05; Fig 1). Subgroup analysis according to stage was performed. When this was done, there was no significant survival difference observed (Fig 2).

Comment Morbidity Reduction of morbidity from lung cancer resections is an ongoing goal of thoracic surgeons. In the current era of health-care cost cutting, it is imperative that new and often expensive technology or procedures are demonstrated to yield quantifiable benefit. Therefore, we performed a retrospective analysis to explore the potential benefit of thoracoscopic surgery to our pneumonectomy patients. The benefits of thoracoscopic lung resections Table 3. Postoperative Complications (Intention-to-Treat Analysis)a

Variable

Thoracoscopic (Including Conversion) Open (n ⫽ 32) (n ⫽ 35) p Value

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Arrhythmias Number needing transfusions Empyema Pneumonia MI BPF Reoperation Death Any complication a

11 (34) 13 (41)

5 (14) 14 (40)

0.054 0.958

1 (3) 6 (19) 1 (3) 2 (6) 6 (19) 1 (3) 21 (51)

1 (3) 6 (17) 0 2 (6) 5 (18) 1 (3) 20 (57)

0.949 0.864 0.292 0.926 0.622 0.949 0.477

Values are number and (%).

BPF ⫽ bronchopleural fistula;

MI ⫽ myocardial infarction.

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Fig 1. Comparison of overall survival between the thoracoscopic (VATS) and open groups (stages I to III) showing a modest advantage in the thoracoscopic group. The converted cases are included in the thoracoscopic group.

are well documented [4, 14 –16]. Most of these benefits are related to a decrease in morbidity. Several authors have demonstrated the feasibility and safety of thoracoscopic or VATS pneumonectomy [8 –13]. The decision to perform a TP rather than a sleeve resection was made by the integration of findings from the computed tomography, bronchoscopy, and VATS exploration. The only difference between the VATS and open cases was the lack of palpation in the former group. Otherwise, identical considerations prevented an operation to spare pulmonary parenchyma. During this time frame, there were 10 open sleeve resections performed, and since then 5 bronchoplasties or sleeve resections have been accomplished thoracoscopically. In our current series of patients, we had lower operative blood loss if we were able to accomplish the pneumonectomy thoracoscopically (Table 2). There was significantly increased blood loss if there was conversion from VATS to thoracotomy. However, our proportion of converted cases dropped progressively during the period of this review, as would be expected from increasing experience with the procedure (data not shown) [13]. There was no statistically significant difference in the need for blood transfusions among the groups. Operative time was significantly longer for TP compared with thoracotomy, more so if it was a converted case. Patients in the thoracoscopic group had a shorter hospital length of stay, but the converted cases had prolonged intensive care unit stay. There was no difference in the incidence of arrhythmias, empyema, myocardial infarction, pneumonia, bronchopleural fistula, reoperation, or death among the groups (Table 3). However, there was a trend toward a higher incidence of atrial arrhythmias in the thoracoscopic group. This could be explained by our low threshold to open the pericardium when we perform TPs. This allows us to safely divide the proximal pulmonary vessels. The proportion of patients in whom this was done is

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not available because this was not specifically captured in our database. The higher incidence of atrial arrhythmias in the VATS group could have been a result of a higher proportion of intrapericardial pneumonectomies in that group. Intrapericardial vessel manipulation may have caused more pericardial and atrial irritation. It appears that an aggregate reduction in morbidity from pneumonectomy is dependent on keeping the conversion rate from VATS to thoracotomy low. As we have gained experience, we have been able to decrease our conversion rate rather than converting to thoracotomy earlier during the procedure.

Overall Survival Some authors have reported improved patient survival after thoracoscopic lobectomies compared with similar procedures through thoracotomy [1, 6]. This has been explained by the reduced immunosuppression from the minimally invasive approach. This could improve a patient’s ability to scavenge residual tumor cells or cells shed at the time of resection from tumor manipulation [1]. It has also been reported that numbers of circulating natural killer and T cells, T-cell oxidative activity, and levels of immunochemokines such as insulin-like growth factor binding protein-3 are higher after VATS than after thoracotomy [6]. Our group has been interested in minimally invasive resections of relatively advanced lung cancers for quite some time. The follow-up of our patients is now long enough to critically evaluate their survival. After a median follow-up of 47 months, we demonstrate a possible survival benefit of TP. However, there is certainly patient selection bias favoring the thoracoscopic group. The patients who had open resections tend to have larger, more advanced tumors. The subgroup analysis supports the assertion that the difference is staged-related, as there was no statistically significant difference in stages I, II, or III between the thoracoscopic and open resection groups. Thus, although we are unable to categorically claim any survival benefit at this time, there is no indication of a detrimental effect from TP on survival. As more surgical groups accumulate experience with TP, propensity-matched, retrospective analyses of prospectively collected data may provide more evidence on the survival benefit from TP or lack thereof. Given the lack of equipoise among surgeons and widespread patient preference for minimally invasive operations, it is unlikely that a prospective randomized study comparing thoracoscopic to open pneumonectomy will be done.

Fig 2. Stage-specific comparison of overall survival between the thoracoscopic (VATS) and open groups showing no statistically significant difference. (A) Stage I survival (6 open, 4 thoracoscopic cases). (B) Stage II survival (14 open, 9 thoracoscopic cases). (C) Stage III survival (14 open, 3 thoracoscopic cases).

Thoracoscopic pneumonectomy for lung cancer can be performed safely with an acceptable conversion rate that is improving and does not adversely affect survival. It is associated with decreased hospital length of stay and lower operative blood loss, but longer operative times. Complication rates between thoracoscopic and open pneumonectomy are similar. Our early experience suggests that the patients in the thoracoscopic group recover faster, but no definite judgment can be made at this time.

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Conclusions

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New studies and additional follow-up are needed to determine whether there is a survival benefit of TP for lung cancer. In the interim, as long as safety and oncologic principles are preserved during the conduct of such procedures, we believe it is reasonable to apply minimally invasive techniques to more complex operations, particularly for frail patients. Improvements to the art of surgery have traditionally evolved in this manner.

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