Local Extension at the Hilum Region Is Associated With Worse Long-Term Survival in Stage I Non- Small Cell Lung Cancers

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1 Local Extension at the Hilum Region Is Associated With Worse Long-Term Survival in Stage I Non- Small Cell Lung Cancers Chang Chen, MD,* Fang Bao, MD,* Hui Zheng, MD, Yi-ming Zhou, MD, Min-wei Bao, MD, Hui-kang Xie, MD, Ge-ning Jiang, MD, Jia-an Ding, MD, and Wen Gao, MD Departments of General Thoracic Surgery and Pathology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai; and Medical School of Suzhou University, Suzhou, China Background. The prognostic significance of hilar structures invasion, which remains undefined for non-small cell lung cancer (NSCLC), may have potential application for cancer staging. Tumor extension along the bronchus and pulmonary vessels was examined for survival significance. Methods. In all, 213 pathologically proved central-type stage I NSCLC cases were enrolled. Four study groups were assigned based on the extent of resections: standard lobectomy (group L, n 32), bronchoplastic procedures (group B, n 94), standard lobectomy combined with pulmonary angioplasty (group A, n 48), and bronchial sleeve resection combined with pulmonary artery angioplasty (group BA, n 39). Univariate and multivariate analysis were performed by the Kaplan-Meier method and the Cox regression model. Results. There were 2 postoperative deaths (pulmonary embolism and serious pulmonary infection). Complications were noted in 39 patients (18.3%). Among these patients, the overall 5-year survival rate was 60.2% 0.05%, with a median survival time of months. The 5-year survival rates of subgroups were 79.5%, 59.7%, 59.0%, and 47.9%, respectively for groups L, B, A, and BA. Univariate analysis indicated tumor size, bronchial invasion, arterial involvement, and type of operation as closely associated with long-term survival. Multivariate analysis indicated that type of operation and tumor size were the most prominent prognostic factors of 5-year survival. Conclusions. Proximal tumor extension into bronchus, invasions into extrapericardial pulmonary vessels, and tumor size were the most important risk factors for 5-year survival with central-type stage I NSCLC. Tumor extension in the hilum was highly related to prognosis and might provide pertinent information to accurately define a tumor ( T ) subclass. (Ann Thorac Surg 2012;93:389 97) 2012 by The Society of Thoracic Surgeons Macroscopic tumor extension and invasion of adjacent organs are highly predictive of poor longterm survival and are important components for defining tumor ( T ) status of all lung cancers. For instance, tumors that invade vital organs, including the trachea, carina, mediastinum, vertebral body, heart, great vessels or esophagus, and recurrent laryngeal nerve, are staged as T4. Numerous studies have found that surgical patients who bear the T4 statue (with adjacent organ/tissue invasion as listed above) had a 5-year survival rate of approximately 22% if the tumors were completely removed, whereas nonsurgical T4 candidates had only a 0% to 7% survival rate [1, 2]. Cancerous involvement of the chest wall, diaphragm, phrenic nerve, mediastinal Accepted for publication Sept 28, *Drs Chang Chen and Fang Bao are both first authors. Address correspondence to Dr Gao, Department of General Thoracic Surgery, Tongji University School of Medicine, Zhengmin Rd, 507, Shanghai , China; shanghaifeike@yahoo.cn. pleura, parietal pericardium, or the main bronchus less than 2 cm distal to the carina was defined as T3 and yielded a 31% rate for 5-year survival [2]. In contrast, for early-stage lung cancers, simply tumor position and tumor size were taken into consideration in the T defining system. However, the prognostic role of both local extension and extent of hilar structure involvement remains unclear. According to the latest TNM classification system (Union Internationale Contre le Cancer [UICC]/American Joint Committee on Cancer [AJCC], seventh edition) [2], stage T1a/T1b refers to a tumor that has a diameter of 3 cm or less and no evidence of invasion more proximal than the lobar bronchus or tumor surrounded by lung or visceral pleura. Further, T2a/T2b refers to tumor sizes of 3 to 5 cm and 5 to 7 cm, main bronchus involvement 2 cm or greater distant to the carina, visceral pleura invasion, or with obstructive pneumonia or atelectasis. Invasion into the hilar structures, either bronchus or pulmonary vessels, has typically been assumed in the same subclass T2a/T2b [2]. Of note, it has not been previously addressed as to whether these hilar involvements differ in long-term outcomes and, corre by The Society of Thoracic Surgeons /$36.00 Published by Elsevier Inc doi: /j.athoracsur

2 390 CHEN ET AL Ann Thorac Surg TUMOR EXTENSION AT HILUM IN STAGE I NSCLC 2012;93: spondingly, whether this result could be applied to delineate different subclasses. Some minor evidence has suggested that vessel involvement and bronchial extension might be associated with worse survival. For example, Macchiarini and colleagues [3] showed that blood vessel invasion was an independent prognostic factor in stage I NSCLC. Additionally, other studies have demonstrated that lymphatic invasion is also associated with adverse prognosis [4 6]. These studies, however, only reveal survival information for cases with microscopic vessel involvement; the prognostic significance of extrapericardial large vessels invasion has been neglected [3 7]. Moreover, little is known about the comparative outcomes between extensive bronchial invasion and major pulmonary vessel involvement. Therefore, a description of the extent of tumor invasion at the hilum region might be prognostically relevant and have further staging significance. We hypothesized that invasion to hilar structures is associated with different long-term outcomes at stage I NSCLC. Such a relationship was examined in the present study. With an aim of purifying the study group, only T1-2N0M0 central-type NSCLC cases were enrolled. Patients and Methods Approval for the study was obtained from the Hospital Ethics Committee. General Information A total of 2,234 NSCLC patients underwent major lung resection for surgical pathology diagnosis of stage I NSCLC (originally based on the sixth edition of the TNM classification system for lung cancers) between April 1994 and December 2008, at the department of thoracic surgery, Shanghai Pulmonary Hospital. According to the study design, two definite inclusion criteria were applied for case selection: pathologically proved N0 (without lymph node metastasis) and central-type NSCLC. First, each case was restaged according to the new edition of the staging system (UICC/AJCC, seventh edition) [2]. All cases bearing T2 disease in the database were reevaluated and redefined as T2a/T2b or T3 based on tumor size measurement. Therefore, cases with a tumor size of 5 cm to 7 cm were deleted as these represented a condition of T2b and were in correspondence with a higher stage (stage IIa) in the new system [2]. Second, the term central-type was verified by examining the records of both preoperative bronchoscopies and pathologic macroscopic descriptions. Evidence of proximal tumor growth to the segmental bronchi, either by macroscopic examination or by bronchoscopy, was mandatorily defined as central-type. Finally, cases with incomplete resections (mostly positive bronchial stump) and bilobectomies, administration of neoadjuvant therapy, diagnosis of metachronous carcinoma, and extrapulmonary carcinoma were excluded. After screening, 213 cases were enrolled from the original database. All patients underwent preoperative evaluations including chest computed tomography, magnetic resonance imaging, upper abdominal computed tomography scan, or ultrasonography examination to exclude remote metastasis. Positron emission tomography was optional. Bronchoscopy was routinely performed to obtain endobronchial information such as the extent of endoluminal neoplasm protrusion, which is obligate to predict a corresponding operative method. Anatomic major pulmonary resections were performed with the aim of a cure for each case. Resection margins underwent onsite frozen section examinations during the operations. An R0 resection was defined if there was no macroscopic residual cancer retained. Routine hilar and mediastinal lymph node dissection was performed, which included the resection of stations 10, 11, 7, and 9 in all cases; stations 2R and 4R for right side cancers; and stations 5 and 6 for the left side. Status of N0 was confirmed according to the pathology data that no intrapulmonary, hilar, or mediastinal lymph node involvement was present. Groupings and Definitions Study groups were assigned according to operative types, which were in accordance with corresponding anatomic structure involvement. Sleeve lobectomies or bronchoplastic procedures were performed if the tumor growth was already invading the lobar orifice or into a larger bronchi; pulmonary angioplasties and tangential arterial resections usually indicate vascular invasion of different extent and length. Except for these two situations, simple lobectomy was technically feasible even though the tumor was located at the hilum. In all, four study groups were assigned (Fig 1): group L (lobectomies) cases with simple lobectomies; no tumor extensions proximal to the lobar bronchus and no pulmonary artery involvement; group B (bronchoplasties) cases with sleeve lobectomies or bronchoplasties, which indicated proximal tumor extension involvement in the lobar orifice but without pulmonary artery invasion; group A (angioplasties) cases with pulmonary angioplasties or tangential pulmonary artery resections; only partial pulmonary artery walls or branches were involved; no bronchial extension was confirmed; and group BA (bronchoangioplasties) cases with double sleeve lobectomies or any types of bronchoplastic surgery combined with tangential artery resections or angioplasties; tumor extension was confirmed along the lobar bronchus and pulmonary artery, and thus necessitated subsequent extensive resections and reconstructions. Data Collection and Follow-Up Clinicopathologic characteristics, including general information and operative methods, were retrieved from the department s database. All patients were followed up by a trained staff every 6 months. Telephone interviews, mailings, or outpatient visits were the main methods of

3 Ann Thorac Surg CHEN ET AL 2012;93: TUMOR EXTENSION AT HILUM IN STAGE I NSCLC 391 Fig 1. All cases were assigned to the four study groups L (lobectomies), B (bronchoplasties), A (angioplasties), and BA (bronchoangioplasties) according to the different hilar structure involvement. (A) Standard lobectomy was performed for group L, (B) bronchoplastic or sleeve bronchial resections for group B; (C) pulmonary angioplastic procedure for group A; and (D) bronchial sleeve resection combined with angioplastic or sleeve vessel resections for group BA. A plus sign ( ) indicates tumor lobar orifice involvement; a minus sign ( ) indicates no lobar orifice involvement. (PA pulmonary artery.) follow-up to obtain information about survival and disease relapse. Survival was measured from the date of surgery to the date of death, or censored at the endpoint of follow-up. Complete follow-up information was obtained in 198 cases (93%); 15 cases (7%) were lost to follow-up. Statistical Analysis Numerical data were depicted in the form of mean and standard deviation. Categorical variables were compared with the contingency table and 2 test. Continuous variables were compared under paired t test and one-way analysis of variance. Survival rates for each group were calculated by the Kaplan-Meier method and further compared using a log rank test. Multivariate analysis of overall survival was performed with a Cox regression model. A p value less than 0.05 was considered statistically significant. Results General Information In all, 213 cases with stage T1-2N0M0, central-type NSCLC were finally enrolled in the present study. All patients underwent lobectomies, with or without bronchoplastic or angioplastic operations, or both. The mean age was years (range, 12 to 80 years); 183 patients (85.9%) were male and 30 (14.1%) were female. There were 133 (62.4%) squamous cell carcinomas, 39 (18.3%) adenocarcinomas, and 41 (19.3%) other histologic types. Tumor size ranged from 0.5 to 5 cm (mean cm). Pathologic specimen examinations showed that lobar takeoff was involved in all 133 bronchoplastic cases, among which 25 cases involved the lower edge of the main bronchus. There were 108 right-sided cancers and 105 left-sided cancers (Table 1). Thirty-two simple lobectomies, 94 bronchoplastic procedures (including 58 bronchial sleeve resections and 36 bronchoplastic operations), 48 pulmonary angioplasties (in addition to simple lobectomies), and 39 sleeve lobectomies combined with pulmonary angioplasty (which included 12 double sleeve resections and 27 tangential pulmonary artery resections) were performed (see Fig 2). Nineteen cases included microscopic tumor invasion into the pulmonary artery. For all angioplastic procedures, no synthetic/biological prosthesis, pericardial patch, or conduit was used for artery reconstructions. No intraoperative deaths occurred. Two patients died within 30 postoperative days, 1 death ascribed to acute pulmonary embolism on the fifth postoperative day, and 1 due to acute respiratory failure and serious pulmonary infection on the 25th postoperative day. Severe compli- Table 1. General Information on Patients According to the Four Different Groups Variable Group L Group B Group A Group BA Age, years Sex, male/female 26/6 88/6 35/13 34/5 Side, left/right 11/21 33/61 30/18 31/8 Histology, Sq/Ad/other 15/8/9 76/7/11 17/16/15 25/8/6 Tumor size, cm cm/ cm/ 2 cm 13/15/4 41/34/19 32/14/2 27/11/1 Complications, yes/no 5/27 16/78 8/40 10/29 Ad adenocarcinoma; Group A angioplasties; Group B bronchoplasties; Group BA bronchoangioplasties; Group L lobectomies; Sq squamous.

4 392 CHEN ET AL Ann Thorac Surg TUMOR EXTENSION AT HILUM IN STAGE I NSCLC 2012;93: Fig 2. Case distributions according to subgroups L (lobectomies), B (bronchoplasties), A (angioplasties), and BA (bronchoangioplasties) and tumor site. A plus sign ( ) indicates tumor lobar orifice involvement; a minus sign ( ) indicates no bronchial extension. (LL left lower lobe; LU left upper lobe; PA pulmonary artery; RL right lower lobe; RM right middle lobe; RU right upper lobe.) cations occurred in 14 patients (6.6%), including bronchopleural fistula (n 3), acute respiratory failure (n 6), upper gastrointestinal bleeding (n 1), hemothorax (n 1), empyema combined with bronchopleural fistula (n 2), and acute respiratory failure combined with upper gastrointestinal bleeding (n 1). Other minor complications experienced by 25 patients included arrhythmia (n 8), prolonged air leak (n 8), secondary pneumonia that necessitated antibiotics treatment and led to prolonged hospital stay (n 6), and pulmonary atelectasis (n 3). Survival Information At the time of follow-up, 67 patients had died because of local recurrence (n 4, 5.9%), distant metastasis (n 44, 65.7%), and other (n 19, 28.4%), as detailed in Table 2. The overall 5-year survival rate was 60.2% 0.05% for the present case series, with a median survival time of months. The 5-year survival rate was, respectively, 79.5%, 59.7%, 59.0%, and 47.9% for the four subgroups, L, B, A, and BA (Fig 3). Proximal Tumor Extension to Bronchus or Onto Vessels Predicts Worse Survival There were obviously three grades of survival among the four study groups, as shown in Figure 3, with group L being the best, group B and group A in the middle, and group BA being the worse. Further analysis indicated that the survival difference was significant among these three classes (p 0.000). There was a significant Table 2. General Information on the 67 Deaths Variable Group L Group B Group A Group BA Cancer-related recurrence Local recurrence 2 2 Bone metastasis Brain metastasis Hepatic metastasis 2 1 Abdominal metastasis 1 Extensive spread Non cancer-related deaths Refractory pulmonary infection 2 1 Acute respiratory failure Hemoptysis Unknown reasons 2 Total Group A angioplasties; Group B bronchoplasties; Group BA bronchoangioplasties; Group L lobectomies.

5 Ann Thorac Surg CHEN ET AL 2012;93: TUMOR EXTENSION AT HILUM IN STAGE I NSCLC 393 Fig 3. The survival rates of the four study groups L (lobectomies [heavy dotted line]), B (bronchoplasties [light solid line]), A (angioplasties [light dotted line]), and BA (bronchoangioplasties [heavy solid line]) were obvious at three grades, with group B and group A being the intermediate. There was no significant difference of survival between group B and group A (p 0.948). Pairwise comparisons revealed a significant difference in survival rate between group L and group B (p 0.036), group L and group A (p 0.047), group B and BA (p 0.008), and group A and BA (p 0.048). survival difference between groups B, A, and BA together versus group L (p 0.008; Fig 4). Such results are highly suggestive that more complex operations and widened extent of resections are closely associated with prominently worse long-term survival for centraltype NSCLC. Fig 5. (A) Survival rates were prominently different between cases with major pulmonary artery (PA) invasion (solid line) and cases without major PA invasion (broken line) by comparing groups A (angioplasties) and BA (bronchoangioplasties) versus groups L (lobectomies) and B (bronchoplasties). (B) There was also a prominent survival difference between cases with bronchial invasion (solid line) and cases without bronchial tumor extension (broken line), by comparing groups B and BA versus groups L and A. Fig 4. Kaplan-Meier survival curves between group L (lobectomies [broken line]) and groups B (bronchoplasties) A (angioplasties) BA (bronchoangioplasties [solid line]). Further, bronchial extension and major blood vessel involvement, as risk factors for survival, were examined with a Kaplan-Meier analysis. Comparison between cases with bronchial extension (a mix of groups B and BA) and cases without (groups L and A) showed a significant difference in 5-year survival (55.9% versus 67.3%, p 0.027). A similar result was obtained pertaining to the condition of artery invasion (groups A and BA versus groups L and B, p 0.010; Fig 5A and 5B). Therefore, these data further supported the hypothesis

6 394 CHEN ET AL Ann Thorac Surg TUMOR EXTENSION AT HILUM IN STAGE I NSCLC 2012;93: Fig 6. Kaplan-Meier survival curves according to tumor size: 2 cm (light dotted line), 2.01 to 3 cm (heavy dotted line); and 3.01 cm to 5 cm (solid line [log rank p 0.008]). that tumor extension into either the bronchi or vessels is highly associated with worse survival. Tumor Size Also a Prominent Prognostic Factor for Central-Type NSCLC Tumor size was the determinant factor for subclasses of stage I cases. In detail, the seventh edition TNM system held that tumor diameters of 2 cm and 3 cm were the criteria to differentiate stages Ia and Ib. Figure 6 shows that tumors with a diameter of 2 cm or less, 2.01 cm to 3 cm, and 3.01 cm to 5 cm, respectively, were obviously associated with gradually decreasing survival (p 0.008). Prognostic Factors of 5-Year Survival Under Univariate and Multivariate Analysis To avoid misunderstanding of phrase tumor extension as a simple histologic infiltration depth within a single structure, type of operation was used to indicate present grouping methods (groups L, B, A, and BA). For the reason that bronchial extension shared similar survival significance with pulmonary vessel involvement (Fig 3), the variable type of operation was redefined as three zones: group L, group B/A, and group BA. Univariate analysis showed that type of operation (p 0.000), tumor size (p 0.008), arterial invasion (p 0.010), and bronchial invasion (p 0.027) were prominent risk factors for 5-year survival rates. Other variables, such as age, sex, tumor location and histologic type, and adjuvant chemotherapy, were irrelevant to prognosis (p 0.05; Table 3). Multivariate analysis with Cox regression further revealed that both tumor size (hazard ratio 1.684, p 0.008) and type of operation (hazard ratio 2.122, p 0.000) were the most significant risk factors. As such, tumor size and type of operation were independent risk factors that were predictive of 5-year survival (Table 4). Comment Non-small cell lung cancers of the hilar region are commonly defined as stage I if there is no lymph node metastasis and the tumor diameter is less than 5 cm, regardless of possibly varied resection extent and surgical techniques. For these central-type lung cancers, however, conditions T1/T2 possibly comprise a wide range of disease composites, considering the various kinds of involved hilar structures. Practically, it could also be quite confusing that tumors requiring complicated and extended resections (such as pulmonary angioplasties or double sleeve lobectomies) share similar long-term survival rates with those of simple lobectomies. Previous studies had emphasized the rationale and how-to-do aspects of these surgical techniques such as sleeve lobectomy, lobectomy with tangential pulmonary artery resection, and double sleeve lobectomy [8 11], but no correlative survival comparisons have been performed from Table 3. Univariate Analysis of Risk Factors of 5-Year Survival Variables Patients (n) 5-Year Survival (%) p Value Type of operation Group L Group B/A Group BA Tumor size 3.01 cm to 5.0 cm cm to 3 cm cm Arterial invasion Yes/no 87/ / Bronchial extension Yes/no 133/ / Age 60 years years Sex Male/female 183/ / Side Left/right 105/ / Histology Squamous Adenocarcinoma Other types Histology Squamous Nonsquamous Adjuvant chemotherapy Yes/no 154/ / Group A angioplasties; Group B bronchoplasties; Group BA bronchoangioplasties; Group L lobectomies.

7 Ann Thorac Surg CHEN ET AL ;93: TUMOR EXTENSION AT HILUM IN STAGE I NSCLC Table 4. Multivariate Analysis of Risk Factors for 5-Year Survival 95% Confidence Interval Variables Hazard Ratio Lower CI Upper CI p Value Type of operation Tumor size Bronchial extension Arterial invasion Histologic type Sex Age Tumor side Adjuvant chemotherapy CI confidence interval. the stand of tumor staging and long-term prognosis. The hypothesis that some subclasses of T1/T2 might be further defined by measuring the extent of involvement of hilar structures, namely, reflected by operative extent, is therefore reasonable. Interestingly, we found that both pulmonary vessel invasion and bronchial extension were the most important risk factors in predicting long-term survival for central-type stage I NSCLC. However, the prognostic significance of the involvement of extrapericardial pulmonary artery branches involvement has not been well evaluated in the literature even though only intrapericardial great vessel involvement has been termed as a T4 condition. The overall 5-year survival of angioplastic procedures, either tangential resection or complete sleeve reconstruction, was commonly between 48.3% and 66.1% for early stage lung cancers [12 14]. In the series by Gabor and colleagues [15] of T1-3N0M0 NSCLC cases, patients with vessel invasion had significantly worse 5-year survival rates of 23.5% compared with 74.5% for patients with innocent pulmonary arteries (p 0.01). Moreover, a meta-analysis yielded a median overall survival of 60 months for sleeve lobectomies and 30 months for an angioplastic group; the overall 5-year survival rates were 50.3% and 38.7%, respectively, for these two groups [16]. Although these data suggest a seemingly inferior survival rate for patients with extrapericardial vessels involvement, no confirmative conclusion can be drawn. The underlying reason is that these studies recruited a mixture of patients with various stages of cancers, and none was specifically designed to compare the prognostic outcomes between different surgical maneuvers. Our study has now confirmed the negative prognostic role of major extrapericardial pulmonary artery involvement. Such results may have similar staging significance with findings that intrapericardial great vessel involvement predicted worse survival and was, therefore, defined as T4. The finding that bronchial extension was also prognostically related is not surprising. Tumor extension along the bronchi might be submucous or peribronchial. Usuda and associates [17] reported a positive relationship between depth of bronchial wall invasion and length of longitudinal extension along the bronchus. Additionally, tumors retained at the distal margin were associated with poor survival [17]. Sakai and coworkers [18] also noted that main bronchus invasion was a statistically independent prognostic factor in primary NSCLC (confidence interval: , p 0.01). Moreover, according to data shown in Figure 3, itis interesting that the prognostic impact of bronchial and vessel extension might be additive. The 5-year survival of combined bronchoangioplastic reconstructions (group BA) was significantly worse compared with that of the other study groups (p 0.05 in all pairwise comparisons and p in the Kaplan-Meier analysis). Similar findings were also noted by Chunwei and associates [13], who identified a 5-year survival rate of 55.5% for sleeve bronchial resections and 33.3% for patients with additional pulmonary angioplasties (p ). Additionally, in the case series by Nagayasu and coworkers [19], the 5-year survival rates were significantly different between the bronchoplastic group and the bronchoangioplastic group: 63.4% and 24.2%, respectively (p ). The relationship between tumor size and survival has been well recognized and verified in numerous studies and has been used to differentiate T1a (tumor size 2 cm), T1b (tumor size 2 cm to 3 cm), and T2a (tumor size 3.01 cm to 5 cm) [2]. With the new lung cancer staging system, the 5-year survivals for T1a, T1b, T2a, were 77%, 71%, and 58%, respectively [2]. The current data yielded similar results with 5-year survivals of 72.3% and 48.4%, respectively, for T1b and T2a hilum-located cancers, and 79.7% for T1a (tumors 2 cm or subcentimeter tumors). Tumor size and the extent of hilar structure invasion were also verified as the most significant prognostic factor by a comprehensive multivariate analysis. The clinical significance of the present findings is that they have potential applications for predicting survival and that they might help more accurately define T staging for these central-type stage I NSCLC. As Shrager and associates [12] suggested, tumors that invade the pulmonary artery might be a T2-defining factor based on the supposition that visceral pleura barrier encroaching

8 396 CHEN ET AL Ann Thorac Surg TUMOR EXTENSION AT HILUM IN STAGE I NSCLC 2012;93: occurred. The results from the present study, moreover, suggest that both vessel invasion and lobar bronchus extension as well as the tumor size variable are prominently prognostically related. These variables, therefore, may be combined to indicate a higher T class (such as T2b or even T3) and a correspondingly tumor upstaging other than stage I. The authors thank Dr Li-ling Zou (Department of Statistics, Tongji University School of Medicine) for her assistance with statistical analysis. References 1. Bernard A, Bouchot O, Hagry O, Favre JP. Risk analysis and long-term survival in patients undergoing resection of T4 lung cancer. Eur J Cardiothorac Surg 2001;20: Detterbeck FC, Boffa DJ, Tanoue LT. The new lung cancer staging system. Chest 2009;136: Macchiarini P, Fontanini G, Hardin JM, Pingitore R, Angeletti CA. Most peripheral, node-negative, non-small-cell lung cancers have low proliferative rates and no intratumoral and peritumoral blood and lymphatic vessel invasion. Rationale for treatment with wedge resection alone. J Thorac Cardiovasc Surg 1992;104: Miyoshi K, Moriyama S, Kunitomo T, Nawa S. Prognostic impact of intratumoral vessel invasion in completely resected pathologic stage I non-small cell lung cancer. J Thorac Cardiovasc Surg 2009;137: Tsuchiya T, Akamine S, Muraoka M, et al. Stage IA nonsmall cell lung cancer: vessel invasion is a poor prognostic factor and a new target of adjuvant chemotherapy. Lung Cancer 2007;56: Hashizume S, Nagayasu T, Hayashi T, et al. Accuracy and prognostic impact of a vessel invasion grading system for stage IA non-small cell lung cancer. Lung Cancer 2009;65: Bodendorf MO, Haas V, Laberke HG, Blumenstock G, Wex P, Graeter T. Prognostic value and therapeutic consequences of vascular invasion in non-small cell lung carcinoma. Lung Cancer 2009;64: Deslaurlers J, Gregoire J, Jacques LF, Piraux M, Guo G, Lacasse Y. Sleeve lobectomy versus pneumonectomy for lung cancer: a comparative analysis of survival and sites of recurrence. Ann Thorac Surg 2004;77: Ferguson MK, Lehman AG. Sleeve lobectomy or pneumonectomy: optimal management strategy using decision analysis techniques. Ann Thorac Surg 2003;76: Venuta F, Ciccone AM. Reconstruction of the pulmonary artery. Semin Thorac Cardiovasc Surg 2006;18: Gómez-Caro A, Garcia S, Reguart N, et al. Determining the appropriate sleeve lobectomy versus pneumonectomy ratio in central non-small cell lung cancer patients: an audit of an aggressive policy of pneumonectomy avoidance. Eur J Cardiothorac Surg 2011;39: Shrager JB, Lambright ES, McGrath CM, et al. Lobectomy with tangential pulmonary artery resection without regard to pulmonary function. Ann Thorac Surg 2000;70: Chunwei F, Weiji W, Xinguan Z, Qingzen N, Xiangmin J, Qingzhen Z. Evaluations of bronchoplasty and pulmonary artery reconstruction for bronchogenic carcinoma. Eur J Cardiothorac Surg 2003;23: Kojima F, Yamamoto K, Matsuoka K, et al. Factors affecting survival after lobectomy with pulmonary artery resection for primary lung cancer. Eur J Cardiothorac Surg 2011;40: e Gabor S, Renner H, Popper H, et al. Invasion of blood vessels as significant prognostic factor in radically resected T1-3N0M0 non-small-cell lung cancer. Eur J Cardiothorac Surg 2004;25: Ma Z, Dong A, Fan J, Cheng H. 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 metaanalysis. Eur J Cardiothorac Surg 2007;32: Usuda K, Saito Y, Nagamoto N, et al. Relation between bronchioscopic findings and tumor size of roentgenographically occult bronchiogenic squamous cell carcinoma. J Thorac Cardiovasc Surg 1993;106: Sakai Y, Ohbayashi C, Kanomata N, et al. Significance of microscopic invasion into hilar peribronchovascular soft tissue in resection specimens of primary non-small cell lung cancer. Lung Cancer 2011;73: Nagayasu T, Matsumoto K, Tagawa T, Nakamura A, Yamasaki N, Nanashima A. Factors affecting survival after bronchoplasty and broncho-angioplasty for lung cancer: single institutional review of 147 patients. Eur J Cardiothorac Surg 2006;29: INVITED COMMENTARY Dr Chen and colleagues [1] address an interesting clinical situation. In patients with small central tumors treated with lobectomy, does undergoing an additional sleeve resection for bronchial or pulmonary artery invasion affect survival? The clinical grouping of these tumors is not entirely clear. Should a T1a/b or T2a tumor that invades or is intimately involved with central bronchi or pulmonary arteries be treated based on that T class or should it be upstaged? If there is a worse prognosis, where should these patients be placed in the staging scheme? The current study addresses this question. It is a well-structured investigation with clear inclusion and exclusion criteria that yields a rather homogeneous patient cohort. The reported follow-up rate of 93% is commendable. The study has the inherent limitations associated with its retrospective nature. The inclusion of patients with pathologic R0 and N0 disease makes broader translation somewhat limited. What the data presented do demonstrate is that tumor size and extent of hilar structure invasion are predictive of survival. Long-term outcomes are followed. The clear cohort inclusion criteria and limited-stage tumors in this analysis allow for comparisons with the current American Joint Committee on Cancer Lung Cancer Staging system, 7th edition. The survival does demonstrate a progressive change in prognosis that corresponds with the extent of invasion or resection. The data support what one would intuitively deduce, ie, no invasion is better and invasion of both bronchus and pulmonary artery needing resection is worse. The need to resect 1 or the other is an intermediate outcome but, somewhat surprisingly, does not convey a terribly worse survival than does the need for no sleeve resection at all by The Society of Thoracic Surgeons /$36.00 Published by Elsevier Inc doi: /j.athoracsur