Lung Cancer 86 (2014) 115–120
Contents lists available at ScienceDirect
Lung Cancer journal homepage: www.elsevier.com/locate/lungcan
Review
Non-small cell lung cancer: When to offer sublobar resection Alan D.L. Sihoe a , Paul Van Schil b,∗ a Division of Cardiothoracic Surgery, Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China b Department of Thoracic and Vascular Surgery, Antwerp University Hospital, Wilrijkstraat 10, Edegem, B-2650 Antwerp, Belgium
a r t i c l e
i n f o
Article history: Received 2 September 2014 Accepted 7 September 2014 Keywords: Lung cancer Segmentectomy Sublobar resection Wedge resection Surgery Thoracotomy Video assisted thoracic surgery
a b s t r a c t Sublobar resection for lung cancer – whether non-anatomic wedge resection or anatomic segmentectomy – has emerged as a credible alternative to lobectomy for the surgical treatment of selected patients with lung cancer. Sublobar resection promises to cause less pulmonary compromise in such patients. Emerging evidence suggests that sublobar resection may offer survival outcomes approaching that of lobectomy for lung cancer patients whose disease meets the following criteria: stage IA disease only; tumor up to 2–3 cm diameter; peripheral location of tumor in the lung; and predominantly ground-glass (non-solid) appearance on CT imaging. The best results are obtained with segmentectomy (as opposed to wedge resection) and complete lymph node dissection. Nevertheless, the evidence is currently still limited, and the above criteria are met only in a minority of patients. Large randomized trials are underway to define the clinical role of sublobar resections, and results are eagerly anticipated. Until that time, lobectomy should still be regarded as the mainstay of surgical therapy for patients with early stage lung cancer at present. © 2014 Elsevier Ireland Ltd. All rights reserved.
1. Introduction Only some 50-odd years ago, the pneumonectomy was considered the surgical procedure offering the best chance of curing a patient with lung cancer [1,2]. It took decades before the lobectomy gradually became the default operation for lung cancer. Recently, the question arose whether sublobar resection comprising a non-anatomic resection of a wedge of lung parenchyma (wedge resection or excision) or removal of an anatomic segment of the lung (segmentectomy), is an oncologically valid procedure. Such a sublobar resection would leave the patient with less respiratory compromise, and (at least with wedge resection) would be a technically simpler operation that ideally complements minimally invasive surgical approaches. Over the years, clinical evidence has generally supported the latter argument. Most thoracic surgeons today would acknowledge that the lobectomy still offers a better chance of curing lung cancer than any form of sublobar resection. But that situation is gradually evolving. Clinical evidence is emerging to show that sublobar resection may have an important role to play in a subset of patients with non-small cell lung cancer (NSCLC).
This article will look at some of the evidence for sublobar resection for NSCLC. Technical aspects of how wedge resections and segmentectomies are performed are beyond the scope of this article, but can be easily read about elsewhere [3]. 2. Evidence from the surgical literature Sublobar resection as a concept is not new. As early as 1973, an actuarial 5-year survival rate of 56% was reported in a series of 69 patients undergoing segmentectomy for bronchogenic carcinoma [4]. In the 1990s, further retrospective studies found no difference in survival when lobectomy and sublobar resections for NSCLC were compared [5,6]. In 1995, the only randomized trial of sublobar resection versus lobectomy for clinical T1N0 NSCLC was published by the Lung Cancer Study Group [7]. In this study, 122 patients with sublobar resection (including 82 segmentectomies) were compared with 125 lobectomies. The death rate per year was 30% higher in the sublobar group with borderline statistical significance (p = 0.08). Moreover, the locoregional recurrence rate in the sublobar group was 300% higher than in the lobectomy group (p = 0.008), with relatively worse results after wedge resection than after segmentectomy. 2.1. Evidence for reduced morbidity?
∗ Corresponding author. Tel.: +32 3 8214360; fax: +32 3 8214396. E-mail addresses: [email protected], [email protected] (P. Van Schil). http://dx.doi.org/10.1016/j.lungcan.2014.09.004 0169-5002/© 2014 Elsevier Ireland Ltd. All rights reserved.
In the Lung Cancer Study Group randomized trial, it was found that the mean drop in Forced Expiratory Volume in one second
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A.D.L. Sihoe, P. Van Schil / Lung Cancer 86 (2014) 115–120
(FEV1) at 12–18 months after a sublobar resection was 5.2% compared to 11.1% after lobectomy (p = 0.04). Since that time, further studies have confirmed that sublobar resection better preserves lung function [8,9]. In addition to lung function preservation, overall morbidity may also be reduced by sublobar resection [10,11]. De Zoysa [12] conducted a systematic literature review on the topic. In three studies morbidity after sublobar resection was reduced – with lower complication rates, shorter hospital stays and better preservation of pulmonary function.
2.2. Evidence for equivalent survival to lobectomy? In the Lung Cancer Study Group randomized trial, sublobar resection was associated with a loco-regional recurrence rate of over 17% [7]. Studies since then have consistently shown locoregional recurrence rates with segmentectomy to be only 2–8% [6,13–16]. Fernando [17] compared outcomes of 124 patients after sublobar resection with those of 167 patients after lobar resection. For tumors smaller than 2 cm, there was no difference in survival. Okada [18] concluded that the 5-year cancer-specific survival rates of patients with stage I disease with a tumor of 20 mm or less were no different if a lobectomy, segmentectomy or wedge resection was performed. In a study of 107 patients undergoing complete (R0) resection for stage IA NSCLC 1 cm or less, Schuchert [19] found no difference in recurrence rates or estimated 5-year survival between patients receiving lobectomy, segmentectomy or wedge resections. In a subsequent retrospective review of 785 consecutive patients undergoing anatomic segmentectomy for solitary pulmonary nodules, the same group found that for patients ultimately found to have pathologic stage IA NSCLC, there was no difference in recurrence rates (14.5% vs 13.9%) or 5-year freedom from recurrence estimates (78% in each group, p = 0.74) when comparing segmentectomy and lobectomy [20]. A study by Kates [21] used the Surveillance, Epidemiology, and End Results (SEER) registry in the United States comparing 688 patients who underwent sublobar resection with 1402 who underwent lobectomy for stage I NSCLC up to 1 cm in size. Overall and lung cancer-specific survival rates were not statistically different. This result seems to support sublobar resection for smaller tumors. Most recently, Altorki [22] identified 347 patients who underwent lobectomy (n = 294) or sublobar resection (n = 53) for NSCLC manifesting as a solid nodule found on CT screening as part of the International Early Lung Cancer Action Program. The 10-year survival rates for sublobar resection and lobectomy were 85% and 86%, respectively (p = 0.86). For those with cancers 20 mm or less, the 10-year survival rates were 88% versus 84%, respectively (p = 0.45). However, there have been reports not so favorable to sublobar resection. Another study using the same SEER database failed to corroborate the earlier findings by Kates [21,23]. Looking at an even larger cohort of 14,473 patients with stage I NSCLC, Whitson found that patients who underwent lobectomy had superior overall and cancer-specific survival rates [23]. Another study by Kraev also demonstrated that patients who underwent lobectomy for tumors
Contents lists available at ScienceDirect
Lung Cancer journal homepage: www.elsevier.com/locate/lungcan
Review
Non-small cell lung cancer: When to offer sublobar resection Alan D.L. Sihoe a , Paul Van Schil b,∗ a Division of Cardiothoracic Surgery, Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China b Department of Thoracic and Vascular Surgery, Antwerp University Hospital, Wilrijkstraat 10, Edegem, B-2650 Antwerp, Belgium
a r t i c l e
i n f o
Article history: Received 2 September 2014 Accepted 7 September 2014 Keywords: Lung cancer Segmentectomy Sublobar resection Wedge resection Surgery Thoracotomy Video assisted thoracic surgery
a b s t r a c t Sublobar resection for lung cancer – whether non-anatomic wedge resection or anatomic segmentectomy – has emerged as a credible alternative to lobectomy for the surgical treatment of selected patients with lung cancer. Sublobar resection promises to cause less pulmonary compromise in such patients. Emerging evidence suggests that sublobar resection may offer survival outcomes approaching that of lobectomy for lung cancer patients whose disease meets the following criteria: stage IA disease only; tumor up to 2–3 cm diameter; peripheral location of tumor in the lung; and predominantly ground-glass (non-solid) appearance on CT imaging. The best results are obtained with segmentectomy (as opposed to wedge resection) and complete lymph node dissection. Nevertheless, the evidence is currently still limited, and the above criteria are met only in a minority of patients. Large randomized trials are underway to define the clinical role of sublobar resections, and results are eagerly anticipated. Until that time, lobectomy should still be regarded as the mainstay of surgical therapy for patients with early stage lung cancer at present. © 2014 Elsevier Ireland Ltd. All rights reserved.
1. Introduction Only some 50-odd years ago, the pneumonectomy was considered the surgical procedure offering the best chance of curing a patient with lung cancer [1,2]. It took decades before the lobectomy gradually became the default operation for lung cancer. Recently, the question arose whether sublobar resection comprising a non-anatomic resection of a wedge of lung parenchyma (wedge resection or excision) or removal of an anatomic segment of the lung (segmentectomy), is an oncologically valid procedure. Such a sublobar resection would leave the patient with less respiratory compromise, and (at least with wedge resection) would be a technically simpler operation that ideally complements minimally invasive surgical approaches. Over the years, clinical evidence has generally supported the latter argument. Most thoracic surgeons today would acknowledge that the lobectomy still offers a better chance of curing lung cancer than any form of sublobar resection. But that situation is gradually evolving. Clinical evidence is emerging to show that sublobar resection may have an important role to play in a subset of patients with non-small cell lung cancer (NSCLC).
This article will look at some of the evidence for sublobar resection for NSCLC. Technical aspects of how wedge resections and segmentectomies are performed are beyond the scope of this article, but can be easily read about elsewhere [3]. 2. Evidence from the surgical literature Sublobar resection as a concept is not new. As early as 1973, an actuarial 5-year survival rate of 56% was reported in a series of 69 patients undergoing segmentectomy for bronchogenic carcinoma [4]. In the 1990s, further retrospective studies found no difference in survival when lobectomy and sublobar resections for NSCLC were compared [5,6]. In 1995, the only randomized trial of sublobar resection versus lobectomy for clinical T1N0 NSCLC was published by the Lung Cancer Study Group [7]. In this study, 122 patients with sublobar resection (including 82 segmentectomies) were compared with 125 lobectomies. The death rate per year was 30% higher in the sublobar group with borderline statistical significance (p = 0.08). Moreover, the locoregional recurrence rate in the sublobar group was 300% higher than in the lobectomy group (p = 0.008), with relatively worse results after wedge resection than after segmentectomy. 2.1. Evidence for reduced morbidity?
∗ Corresponding author. Tel.: +32 3 8214360; fax: +32 3 8214396. E-mail addresses: [email protected], [email protected] (P. Van Schil). http://dx.doi.org/10.1016/j.lungcan.2014.09.004 0169-5002/© 2014 Elsevier Ireland Ltd. All rights reserved.
In the Lung Cancer Study Group randomized trial, it was found that the mean drop in Forced Expiratory Volume in one second
116
A.D.L. Sihoe, P. Van Schil / Lung Cancer 86 (2014) 115–120
(FEV1) at 12–18 months after a sublobar resection was 5.2% compared to 11.1% after lobectomy (p = 0.04). Since that time, further studies have confirmed that sublobar resection better preserves lung function [8,9]. In addition to lung function preservation, overall morbidity may also be reduced by sublobar resection [10,11]. De Zoysa [12] conducted a systematic literature review on the topic. In three studies morbidity after sublobar resection was reduced – with lower complication rates, shorter hospital stays and better preservation of pulmonary function.
2.2. Evidence for equivalent survival to lobectomy? In the Lung Cancer Study Group randomized trial, sublobar resection was associated with a loco-regional recurrence rate of over 17% [7]. Studies since then have consistently shown locoregional recurrence rates with segmentectomy to be only 2–8% [6,13–16]. Fernando [17] compared outcomes of 124 patients after sublobar resection with those of 167 patients after lobar resection. For tumors smaller than 2 cm, there was no difference in survival. Okada [18] concluded that the 5-year cancer-specific survival rates of patients with stage I disease with a tumor of 20 mm or less were no different if a lobectomy, segmentectomy or wedge resection was performed. In a study of 107 patients undergoing complete (R0) resection for stage IA NSCLC 1 cm or less, Schuchert [19] found no difference in recurrence rates or estimated 5-year survival between patients receiving lobectomy, segmentectomy or wedge resections. In a subsequent retrospective review of 785 consecutive patients undergoing anatomic segmentectomy for solitary pulmonary nodules, the same group found that for patients ultimately found to have pathologic stage IA NSCLC, there was no difference in recurrence rates (14.5% vs 13.9%) or 5-year freedom from recurrence estimates (78% in each group, p = 0.74) when comparing segmentectomy and lobectomy [20]. A study by Kates [21] used the Surveillance, Epidemiology, and End Results (SEER) registry in the United States comparing 688 patients who underwent sublobar resection with 1402 who underwent lobectomy for stage I NSCLC up to 1 cm in size. Overall and lung cancer-specific survival rates were not statistically different. This result seems to support sublobar resection for smaller tumors. Most recently, Altorki [22] identified 347 patients who underwent lobectomy (n = 294) or sublobar resection (n = 53) for NSCLC manifesting as a solid nodule found on CT screening as part of the International Early Lung Cancer Action Program. The 10-year survival rates for sublobar resection and lobectomy were 85% and 86%, respectively (p = 0.86). For those with cancers 20 mm or less, the 10-year survival rates were 88% versus 84%, respectively (p = 0.45). However, there have been reports not so favorable to sublobar resection. Another study using the same SEER database failed to corroborate the earlier findings by Kates [21,23]. Looking at an even larger cohort of 14,473 patients with stage I NSCLC, Whitson found that patients who underwent lobectomy had superior overall and cancer-specific survival rates [23]. Another study by Kraev also demonstrated that patients who underwent lobectomy for tumors
