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Ann Thorac Surg 2003;76:1782-1788
© 2003 The Society of Thoracic Surgeons

Original article: general thoracic

Sleeve lobectomy or pneumonectomy: optimal management strategy using decision analysis techniques

Mark K. Ferguson, MDa*, Amy G. Lehman, BAa

a Department of Surgery, The University of Chicago, Chicago, Illinois, USA

Accepted for publication June 3, 2003.

* Address reprint requests to Dr Ferguson, Department of Surgery, The University of Chicago, 5841 S. Maryland Ave, MC5035, Chicago, IL60637, USA.
e-mail: mferguso{at}surgery.bsd.uchicago.edu


   Abstract
Top
 Abstract
Introduction
 Material and methods
 Results
 Comment
 Acknowledgments
 References
 
BACKGROUND: The choice between sleeve lobectomy and pneumonectomy is controversial for patients with early-stage lung cancer and who have acceptable lung function.

METHODS: We performed a meta-analysis of results of sleeve lobectomy and pneumonectomy published in English from 1990 to 2003. A decision model was developed with 5-year survival, quality-adjusted life years (QALY), and cost effectiveness as the outcomes, and sensitivity analyses were performed.

RESULTS: The model favored sleeve lobectomy (3.5 percentage point survival advantage) when the reward was 5-year survival; the results were influenced primarily by the 5-year survival rates for patients who did not develop recurrent cancer. Sleeve lobectomy was strongly favored when the reward was QALY (1.53 QALY advantage). Sleeve lobectomy was more cost effective than pneumonectomy, and had an incremental cost effectiveness ratio of $1,300/QALY.

CONCLUSIONS: In patients with anatomically appropriate early-stage lung cancer, sleeve lobectomy offers better long-term survival and quality of life than does pneumonectomy and is more cost effective.


   Introduction
Top
 Abstract
 Introduction
Material and methods
 Results
 Comment
 Acknowledgments
 References
 
Despite substantial improvements in multimodality therapy, resection remains the most important element in potentially curative therapy for lung cancer. Pneumonectomy originally was considered the only appropriate surgical therapy for localized lung cancer, and the transition from pneumonectomy to lobectomy as the standard procedure was controversial and slow. Controversy continues over appropriate management of patients with centrally located tumors. Bronchial sleeve resection was introduced by Price-Thomas in 1947 as a means of conserving lung parenchyma in patients with compromised pulmonary function, and the first sleeve lobectomy was reported by Allison in 1954 [1, 2]. It has only gradually gained acceptance as a standard resection technique for lung cancer. Issues of concern include the possible increased risk of local recurrence, complications related to the bronchial anastomosis, resultant increased costs of care, and whether this more limited operation puts patients at a disadvantage with respect to long-term survival.

Several recent studies suggest that sleeve resection should be used routinely in the management of patients with anatomically appropriate centrally located tumors, even in patients with sufficient pulmonary reserve to permit pneumonectomy [3–6]. The reports contend that local recurrence is not an important issue, that long-term survival is similar to or better than after pneumonectomy, and that quality of life is better than after pneumonectomy. Unfortunately, stage distribution between the two techniques is significantly different in most reports, and careful comparisons between the techniques regarding survival and local recurrence rates with appropriate stage stratification have not been performed. In addition, no formal information is available in these reports regarding quality of life after the two types of operations.

We elected to study the role of sleeve resection compared with pneumonectomy in patients with early-stage non–small cell lung cancer using decision analysis techniques. This methodology lends itself to the analysis of multiple disparate published results and permits comparisons of outcomes using a number of different end points, or rewards, such as survival and cost effectiveness. We sought to determine whether sleeve lobectomy or pneumonectomy offers better survival and quality-adjusted survival and which procedure is more cost effective for patients with early-stage non–small cell lung cancer.


   Material and methods
Top
 Abstract
 Introduction
 Material and methods
Results
 Comment
 Acknowledgments
 References
 
A MEDLINE search of reports published in English from 1990 to 2003 using the terms "sleeve resection and/or pneumonectomy" and "lung neoplasm" was performed and yielded 99 articles. All abstracts were reviewed and a related article search was performed on appropriate abstracts. Articles were selected by a consensus of 2 reviewers that satisfied these predetermined criteria: at least 20 patients in each surgical group; surgical procedures were classified according to stage for stage I and stage II patients [7]; operative mortality was reported or calculable by stage; and 5-year survival was reported by stage. In some cases, nodal status (N0, N1) was used as a surrogate for stage I or stage II disease, respectively. Data that concerned malignancies other than non–small cell lung cancer; information for patients with other than stage I or stage II disease; or carinal, tracheal, and arterial sleeve resection were discarded.

Meta-analyses of the resultant data were performed to produce estimates for appropriate nodes of the decision model. Survival within each study was calculated assuming an equal distribution of stage I and stage II patients to correct for the dissimilar distributions of these stages between sleeve lobectomy and pneumonectomy series. Cost information for surgery was obtained from data collected on 100 patients who underwent thoracotomy for lung resection at the University of Chicago Medical Center 1998 to 2001 under a protocol that was approved by the Institutional Review Board and for which specific patient consent was not required. Costs were prorated for the type of procedure based on mean duration of hospitalization. Costs for other therapies were abstracted from recent literature. All costs were normalized to 2002 dollars using the Consumer Price Index conversion factor. Estimates for other parameters, including survival after recurrent disease and quality of life estimates, were derived from studies published during the same time interval. Isolated local/regional recurrence was defined as recurrence of the original cancer in the bronchus, peribronchial soft tissues, or ipsilateral hilar or mediastinal lymph nodes in order to focus on the differing risks for isolated local recurrence that were procedure dependent. Other patterns of recurrence, including those in the ipsilateral hemithorax, in distant sites, or any local/regional recurrence that was accompanied by a recurrence in another site, were classified as other recurrences. Appropriate ranges were inserted into the model based on 95% confidence intervals (CI) where available or on estimates when necessary.

The model was constructed using a dichotomous choice between sleeve lobectomy and pneumonectomy for patients with stage I and stage II disease (Fig 1). The model assumed that isolated local recurrences after sleeve lobectomy could be treated in a variety of ways including re-resection (completion pneumonectomy), whereas isolated local recurrences after pneumonectomy could not be treated by further resection. Other recurrences were assumed to be managed with either chemotherapy alone or with a combination of chemotherapy and radiation therapy. Survival after recurrence was assumed to be related to the type of recurrence and whether re-resection could be performed for an isolated local recurrence.



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  		Fig 1. Decision model with sleeve lobectomy and pneumonectomy as the options at the decision node (square). At chance nodes (circles), treatment and disease states are assigned probabilities of occurrence. Terminal nodes (triangles) are assigned outcomes values, including survival, QALYs, and cost effectiveness. Values are provided in Table 2. Based on values at terminal nodes and the chance of reaching each terminal node, calculations are performed right to left to yield overall values for each option at the decision node. (CRT = chemoradiotherapy; CT = computed tomography; Op = operative; QALY = quality-adjusted life years; RT = radiotherapy.)

 

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  		Table 2. Probabilities of Events and Utilities of Health States

 
Outcomes included overall survival (expressed as percent survival at 5 years using Kaplan-Meier estimates), quality-adjusted life years (QALY), and cost effectiveness, and were calculated from the perspective of the medical center. Quality adjusted life years were calculated from the product of survival duration for a given health state and the quality of life (QOL) estimate. The data for QOL after surgery were derived from five studies that used three different tools to assess QOL (Short Form 36 [SF-36], European Organization for Research and Treatment of Cancer Quality of Life Questionnaire [EORTC QLQ], and Quality of Life Index [QLI]). The tools were self-administered in three instances and administered by a trained and independent observer in the other instances. The results of QOL ratings were linearly transformed to a scale that scored QOL on a continuum from 0 (very poor) to 1 (optimal health). This resulted in three estimates of global QOL during the early postoperative period and six estimates of global QOL long-term postoperatively. In some studies, median survival was not reached by the end of the reporting period. In these instances, median survival was estimated based on the ratios between 5-year survival values. One-way sensitivity analyses were performed on all variables to identify those variables that influenced the outcomes in the model, and threshold values were calculated to determine inflexion points at which the alternative choice was superior. Two-way sensitivity analyses were performed on clinically important variables that influenced the model outcomes. Statistical analyses were performed with Minitab 12.1 (Minitab, Inc, State College, PA), and Data Pro (release 7.0, TreeAge Software, Inc, Williamstown, MA) was used for all decision analyses. Data are expressed as mean ± SD.


   Results
Top
 Abstract
 Introduction
 Material and methods
 Results
Comment
 Acknowledgments
 References
 
A total of 12 articles met the defined criteria and were used for data abstraction for 860 sleeve lobectomy patients and 746 pneumonectomy patients (Table 1) [8–21]. The distribution of stages between the two groups differed significantly (stages I and II: 450 and 410 for sleeve resection; 250 and 496 for pneumonectomy; p < 0.001). Age distributions for the two surgical groups were not available in the published articles. However, mean ages for patients in the sleeve lobectomy group (61.0 years; 10 reports) did not differ from mean ages in the pneumonectomy group (60.5 years; five reports). The weighted mean operative mortality was 4.1% (Cl, 2.3% to 5.9%) after sleeve lobectomy and 6.0% (Cl, 1% to 11%) after pneumonectomy (p = 0.3) (Table 2). The likelihood of isolated local/regional recurrence was substantially higher after sleeve lobectomy (20%) than it was after pneumonectomy (10%) [9, 11, 13, 18]. Isolated local/regional recurrence as a fraction of all recurrences was higher for sleeve lobectomy (51%) than it was for pneumonectomy (20%), and was higher than for separately reported series of major lung resections for stages I and II non–small cell cancer (30%) [22–28]. There was no difference in mean 5-year survival (51.4 ± 10.1% for sleeve lobectomy vs 49.1 ± 5.5% for pneumonectomy; p = 0.6). Mean median survivals were 70.5 ± 16.2 months for sleeve lobectomy and 55.2 ± 6.6 months for pneumonectomy (p = 0.024).


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  		Table 1. Outcomes of Sleeve Lobectomy and Pneumonectomy for Stage I and II Non–Small Cell Lung Cancer Reported in the Literature From 1990 to 2003

 
Using an outcome of 5-year survival, the decision model slightly favored sleeve lobectomy (52.4%) over pneumonectomy (48.7%). One-way sensitivity analyses demonstrated that the outcome was influenced by the risk of isolated local/regional recurrence in patients undergoing sleeve lobectomy (threshold value, 28%), by the risk of other recurrence in both groups (threshold values, 13% for pneumonectomy and 28% for sleeve lobectomy), and by 5-year survival in patients without recurrent cancer undergoing either operation (threshold values, 73% for pneumonectomy and 70% for sleeve lobectomy). Two-way sensitivity analyses illustrated the relationships for other recurrences (Fig 2) and for 5-year survival in patients without recurrent cancer (Fig 3) for both options, and indicate the preference for sleeve lobectomy in this model.



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  		Fig 2. Two-way sensitivity analysis for the risk of other recurrence with 5-year survival as the outcome. Regions of favored therapy are represented in white (sleeve lobectomy) and grey (pneumonectomy) based on corresponding variable values. The box illustrates the range of values tested in the model, and the preponderance of the white area within the box indicates that sleeve lobectomy is favored by the model.

 


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  		Fig 3. Two-way sensitivity analysis of survival for patients without recurrent lung cancer with 5-year survival as the outcome. Regions of favored therapy are represented in white (sleeve lobectomy) and grey (pneumonectomy) based on corresponding variable values. The box illustrates the range of values tested in the model, and the preponderance of the white area within the box indicates that sleeve lobectomy is favored by the model.

 
Using an outcome of QALY, the decision model strongly favored sleeve lobectomy over pneumonectomy (4.37 vs 2.84 QALY). One-way sensitivity analyses did not identify any variables that influenced the outcome. Sleeve lobectomy was more cost effective than pneumonectomy, and demonstrated an incremental cost effectiveness ratio of $1,300/QALY (Table 3). One-way sensitivity analyses did not identify any variables that influenced the outcome.


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  		Table 3. Outcomes of Cost Effectiveness Analysis

 

   Comment
Top
 Abstract
 Introduction
 Material and methods
 Results
 Comment
Acknowledgments
 References
 
Lung cancer accounts for more cancer deaths in the United States than colorectal, breast, and prostate cancer combined. Early diagnosis and surgical therapy for early-stage lung cancer are the best current methods for optimizing long-term survival. Surgical approaches for lung cancer vary from limited parenchymal resection accompanied by nodal sampling for peripheral, small, early-stage cancers to pneumonectomy and radical mediastinal nodal dissection for centrally located tumors with clinical nodal involvement. Preoperative cardiopulmonary function and the amount of pulmonary parenchyma resected influence postoperative functional performance and likely affect postoperative quality of life. Therefore, individualization of technique selection is important for survival and quality of life outcomes.

Initial efforts at parenchyma-sparing operations such as sleeve lobectomy focused on patients with limited pulmonary reserve who were not candidates for pneumonectomy. Based on a favorable experience with such patients, the indications for such procedures expanded to include patients with anatomically favorable tumors regardless of their preoperative pulmonary status. The theory was that preservation of lung parenchyma was likely to reduce the risks of operative mortality and should improve functional capacity and possibly quality of life in the long term.

The trade-offs for these benefits include a theoretical increase in the risk of several problems: anastomotic complications such as dehiscence, vascular fistula, and stenosis, leading to an increase in costs; local/regional recurrence of the original cancer; and new primary lung cancer. Local/regional recurrence comprises several entities, including anastomotic or bronchial stump recurrence, local nodal recurrence, and regional nodal recurrence. The risk of the first two of these may be increased after sleeve lobectomy because less peribronchial soft tissue is removed and two bronchial resection margins exist as compared with one after pneumonectomy. The risk of developing a second primary lung cancer is increased because of the increased amount of remaining pulmonary parenchyma after lung conservation surgery. The risk of a new primary lung cancer after lobectomy is estimated at between 1% and 2% annually [29–31]. Theoretically, this risk is reduced by one-third after pneumonectomy because of the lesser amount of remaining parenchyma.

These factors have led to some controversy about the relative benefits of parenchyma-sparing operations in patients with good pulmonary reserve. There are ardent advocates for sleeve lobectomy. In contrast, few surgeons recommend the routine use of pneumonectomy, but apply this technique in exceptional situations in which standard lobectomy or bilobectomy is not an option. Comparisons between the two techniques have been hampered by limited reporting of outcomes for each and by differences in stage distribution among the patients undergoing each procedure.

Our review of the recent published literature was able to address some of these issues. Although the results did not differ significantly, operative mortality was confirmed to be somewhat higher after pneumonectomy than after sleeve lobectomy, giving some support to the contention that sleeve lobectomy is a safer operation in the hands of experienced surgeons. Importantly, isolated local/regional recurrence rates were substantially higher after sleeve lobectomy than after pneumonectomy, whereas other recurrence rates did not differ between the two operations. Despite this fact, 5-year survival rates were similar for the two operations when corrections for stage distribution were calculated. Use of 5-year survival as an outcome in the decision model slightly favored sleeve lobectomy over pneumonectomy for managing stage I and II non–small cell lung cancer.

The similarity in 5-year survival rates for the two procedures suggests that pneumonectomy patients die more often of intercurrent disease than do sleeve lobectomy patients, raising concerns about long-term risks of fatal cardiopulmonary limitations in these patients. Quantifying the risk of cardiopulmonary limitation after pneumonectomy is difficult. It has been known for more than half a century that some patients have substantial functional decrements, although they often continue to report quite satisfactory global quality of life (QOL) [32–36]. Two recent reports suggest that QOL may be related to the amount of lung resected, as judged by the type of operation or by estimated postoperative diffusing capacity [33, 35]. Use of these QOL estimates in the calculation of QALY as an outcome shifted the outcome strongly in favor of sleeve lobectomy for the management of these patients.

There are limited data regarding QOL after major lung resection. The data that are available are not consistent in the degree of return of functional capacity, the time necessary to reach a functional plateau postoperatively, the relationship between functional capacity and overall perceived quality of life, or the level of perceived QOL long term postoperatively. Each of these values is vital in the estimation of QALY-related outcomes after major lung resection. It is important that additional prospective efforts at evaluating QOL outcomes after thoracic surgery be undertaken.

Our analysis demonstrated that sleeve lobectomy was more cost effective than pneumonectomy. The calculation was somewhat trivial owing to the small increment in costs accompanying sleeve lobectomy and the large increase in QALY that attends that procedure. The results demonstrate that the incremental cost effectiveness ratio was well within the commonly accepted willingness-to-pay threshold [44].

One possible concern regarding this study design was the comparison of patients in the sleeve lobectomy group who might not have tolerated pneumonectomy to patients in the pneumonectomy group, who presumably had better cardiopulmonary function. Overall, survival and cost effectiveness outcomes were superior for sleeve lobectomy, even though those patients were, on average, less able to tolerate pneumonectomy and presumably had worse baseline cardiopulmonary function and predicted long-term survival as a result. Because the bias was against sleeve lobectomy and the results were strongly in favor of this operation, this should not be a major issue in interpreting the results.

Our findings suggest that performance of a sleeve lobectomy rather than a pneumonectomy for patients who are anatomically appropriate, regardless of underlying cardiopulmonary status, provides an overall survival and QOL advantage. Reasons for this likely include the relatively low overall risk of isolated local/regional recurrence after either operation and improved postoperative cardiopulmonary status after sleeve lobectomy owing to preservation of lung parenchyma. Our calculations were performed using data derived from limited retrospective studies. The use of large volumes of prospectively collected data, such as may become available with the advent of the Society of Thoracic Surgeons General Thoracic Surgery Database, will be invaluable in refining estimates of benefit for either of these operations.


   Acknowledgments
Top
 Abstract
 Introduction
 Material and methods
 Results
 Comment
 Acknowledgments
References
 
We thank Dr David Meltzer and Anirban Basu for their assistance in the preparation of this manuscript.


   References
Top
 Abstract
 Introduction
 Material and methods
 Results
 Comment
 Acknowledgments
 References
 

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Does sleeve lobectomy concomitant with or without pulmonary artery reconstruction (double sleeve) have favorable results for non-small cell lung cancer compared with pneumonectomy? A meta-analysis
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Surgical Techniques and Results for Partial or Circumferential Sleeve Resection of the Pulmonary Artery for Patients with Non-Small Cell Lung Cancer
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Morbidity, mortality, and long-term survival after sleeve lobectomy for non-small cell lung cancer
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P. N. Chhajed, R. Eberhardt, H. Dienemann, A. Azzola, M. H. Brutsche, M. Tamm, and F. J.F. Herth
Therapeutic bronchoscopy interventions before surgical resection of lung cancer.
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B. F. Meyers, F. Haddad, B. A. Siegel, J. B. Zoole, R. J. Battafarano, N. Veeramachaneni, J. D. Cooper, and G. A. Patterson
Cost-effectiveness of routine mediastinoscopy in computed tomography- and positron emission tomography-screened patients with stage I lung cancer
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S.-i. Takeda, H. Maeda, M. Koma, Y. Matsubara, N. Sawabata, M. Inoue, T. Tokunaga, and M. Ohta
Comparison of surgical results after pneumonectomy and sleeve lobectomy for non-small cell lung cancer.: Trends over time and 20-year institutional experience
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P. Bagan, P. Berna, J. C. Das Neves Pereira, F. Le Pimpec Barthes, C. Foucault, A. Dujon, and M. Riquet
Sleeve Lobectomy Versus Pneumonectomy: Tumor Characteristics and Comparative Analysis of Feasibility and Results
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Early and long-term results of lung resection for non-small-cell lung cancer in patients with severe ventilatory impairment
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Bronchovascular Versus Bronchial Sleeve Resection for Central Lung Tumors
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