Outcomes and pulmonary function after sleeve lobectomy compared with pneumonectomy in patients with non–small cell lung cancer

Abstract

Background

Sleeve lobectomy is recommended to avoid pneumonectomy and preserve pulmonary function in patients with central lung cancer. However, the relationship between postoperative pulmonary functional loss and resected lung parenchyma volume has not been fully characterized. The aim of this study was to evaluate the relationship between pulmonary function and lung volume in patients undergoing sleeve lobectomy or pneumonectomy.

Methods

A total of 61 lung cancer patients who had undergone pneumonectomy or sleeve lobectomy were analyzed retrospectively. Among them, 20 patients performed pulmonary function tests, including vital capacity (VC) and forced expiratory volume in 1 s (FEV1) tests, preoperatively and then about 6 months after surgery. VC and FEV1 ratios were calculated (measured postoperative respiratory function/predicted postoperative respiratory function) as the standardized pulmonary functional loss ratio.

Results

Thirty‐day operation‐related mortality was significantly lower after sleeve lobectomy (3.2%) than pneumonectomy (9.6%). The 5‐year relapse‐free survival rate was 46.67% versus 29.03%, and the 5‐year overall survival rate was 63.33% versus 38.71% in patients receiving sleeve lobectomy versus pneumonectomy. The VC ratio in the pneumonectomy group was better than in the sleeve lobectomy group (1.003 ± 0.117 vs. 0.779 ± 0.12; p = 0.0008), as was the FEV1 ratio (1.132 ± 0.226 vs. 0.851 ± 0.063; p = 0.0038).

Conclusions

Both short‐term and long‐term outcomes were better with sleeve lobectomy than pneumonectomy. However, actual postoperative pulmonary function after pneumonectomy may be better than clinicians expect, and pneumonectomy should still be considered a treatment option for patients with sufficient pulmonary reserve and in whom sleeve lobectomy is less likely to be curative.

Sleeve lobectomy should be considered as the first strategy in any case of lung cancer over pneumonectomy. However, the standardized pulmonary functional loss ratios for vital capacity (VC) and forced expiratory volume in 1 s (FEV1) (measured postoperative respiratory function/predicted postoperative respiratory function × 100) are better in the pneumonectomy group than in the sleeve lobectomy group. Pneumonectomy still should be a treatment option.

INTRODUCTION

For patients unable to tolerate a pneumonectomy because of an inadequate pulmonary reserve, sleeve lobectomy has a definite role in the surgical management of non–small cell lung cancer (NSCLC), thanks to its greater sparing of the lung parenchyma. ¹ , ² , ³ , ⁴ By comparison, pneumonectomy is associated with higher morbidity and mortality, poorer quality of life, and cardiopulmonary dysfunction. ¹ , ⁵ Some observational studies have demonstrated an association between sleeve resections and lower perioperative mortality rates with equivalent oncologic outcomes as compared to pneumonectomy. ² , ⁶ , ⁷ According to a multilevel analysis using data from the national data base, ⁵ sleeve resection is associated with improved short‐term outcomes as well as improved overall survival (OS). However, whether sleeve resection is sufficiently curative to be indicated for patients who could tolerate pneumonectomy continues to be debated. ²

Several reports have shown the superiority of sleeve lobectomy over pneumonectomy for preserving postoperative pulmonary function. ⁸ , ⁹ , ¹⁰ , ¹¹ They all recommend that sleeve lobectomy be the first‐choice strategy whenever possible, because there is preservation of lung parenchyma and therefore, a better lung function and quality of life. ¹⁰ However, the relationship between postoperative functional loss and resected lung volume has not been fully characterized.

Our aim was to evaluate the relationship between pulmonary function and resected lung parenchyma volume in patients undergoing sleeve lobectomy or pneumonectomy and to compare the surgical procedures with respect to postoperative pulmonary function.

METHODS

Patients

All experimental protocols were approved by the institutional review board (IRB) at Akita University Hospital (approval number: 2679), and all samples were collected under IRB Protocol No. 2679, which allows collection of tissue and medical record with consent or waiver of consent when no personalized health information is required, as was the case in this study. From among a total of 1149 NSCLC patients, the medical records of 61 patients who underwent pneumonectomy or sleeve lobectomy at our institute between January 2004 and December 2019 were retrospectively reviewed. The patients' characteristics are listed in Table 1. Ten patients received pre‐operative chemotherapy or radiation. The cases that were lost to follow‐up or suffered complications preventing postoperative pulmonary function testing were excluded from a second study comparing pulmonary function tests. A total of 20 patients who performed pulmonary function tests after undergoing pneumonectomy (n = 11) or sleeve lobectomy (n = 9) were deemed eligible for comparison. A diagram of the selection process is shown in Figure 1. These patients' characteristics are listed in Table 2.

TABLE 1.

Characteristics of patients who underwent pneumonectomy or sleeve lobectomy

Characteristic	Pneumonectomy (N = 31)	Sleeve lobectomy (N = 30)	p‐value
Age (yr)	65.23 ± 10.47	64.93 ± 8.25	0.9057
Sex			0.2205
Male	23	26
Female	8	4
Histology			0.0274
Squamous	13	21
Non‐squamous	18	9
Tumor location side			0.0002
Left	23	10
Right	8	20
Lobe			0.0119
Upper lobe	15	25
Middle lobe	1	1
Lower lobe	15	4
Size (mm)	49.87 ± 18.00	35.39 ± 13.43	0.0012
p‐Nodal status			0.7418
N0	8	10
N1	10	10
N2	13	10
p‐Stage			0.1715
IA/IB	2	6
IIA/IIB	6	8
IIIA/IIIB	23	16
Operation time (min)	202.9 ± 57.71	319.44 ± 59.48	0.004
Blood loss (mL)	294.9 ± 300.99	287.93 ± 241.79	0.9232
Duration of chest drainage (day)	2.27 ± 0.75	9.00 ± 3.43	<0.001
Postoperative hospitalization (day)	30.00 ± 37.31	27.00 ± 21.54	0.6595
Mortality (%)
30 day	3.2	0
90 day	9.6	0
Chemotherapy	4	6
Radiotherapy	0	4
Incidence of complication, total	10	10
Acute respiratory distress syndrome	3	0
Bronchopleural fistula	1	2
Prolonged air leakage	0	2
Recurrent laryngeal nerve palsy	2	0
Other	4	6

FIGURE 1.

Flow diagram illustrating the selection process for the 61 patients who underwent pneumonectomy or sleeve lobectomy among 1149 non–small cell lung cancer patients. Among those selected, pulmonary function of evaluated in 20 patients who underwent pneumonectomy (n = 11) or sleeve lobectomy (n = 9) and then performed pulmonary function tests postoperatively

TABLE 2.

Characteristics of patients who performed pulmonary function tests after undergoing pneumonectomy or sleeve lobectomy

Characteristic	Pneumonectomy (N = 11)	Sleeve lobectomy (N = 9)	p‐value
Age (yr)	61.27 ± 12.93	60.44 ± 8.23	0.8763
Sex			0.6595
Male	9	8
Female	2	1
Histology			0.199
Squamous	3	5
Non‐squamous	8	4
Tumor location, side			0.3907
Left	8	4
Right	3	5
Site			0.4287
Upper lobe	6	7
Middle lobe	1	1
Lower lobe	4	1
Size (mm)	45.4 ± 18.3	39.4 ± 10.4	0.4726
Atelectasis and/or bronchial obstruction	5	5	0.6531
p‐Nodal status			0.1096
N0	1	4
N1	5	1
N2	5	4
p‐Stage			0.2136
IA/IB	1	2
IIA/IIB	1	3
IIIA/IIIB	9	4

Surgical procedure

All patients received standard pre‐ and intraoperative care. Sleeve lobectomy was our procedure of first choice for anatomically and progressively suitable carcinomas. Pneumonectomy and sleeve lobectomy were designated with a macroscopically safe margin. If the sleeve lobectomy was incomplete or intraoperative pathological analysis revealed a malignant‐positive surgical margin, the surgeon converted to pneumonectomy at the discretion of the surgical team before or during the surgery.

Pulmonary function tests

To assess the resected lung volume, the predicted‐postoperative pulmonary function was calculated and compared with the actual measured value of pulmonary function at 1 and 6 months after surgery. Pulmonary function was tested with a spirometer (CHE‐ STAC 8800, CHEST M. I.) at our institute and evaluated using American Thoracic Society standards. ¹² The vital capacity (VC) and forced expiratory volume in 1 s (FEV1) were measured in patients preoperatively and postoperatively within 6 months after surgery. The measurements were documented as the actual volume as well as the ratio of the actual volume to the standard volume determined based on the age, sex, and height of the patient as described in our earlier report. ¹³ The postoperative absolute reductions in VC and FEV1 were calculated using the formula: $\left[\text{postoperative value}\right]/\left[\text{preoperative value}\right]\times 100\left(\%\right).$

The ratio of the actual degree of postoperative functional loss to the resected lung volume was calculated using the formula:

$$\left(\left[\text{measured postoperative value}\right]-\left[\text{predicted postoperative value}\right]\right)/\left[\text{predicted postoperative value}\right]\times 100\left(\%\right).$$

Briefly, the predicted‐postoperative pulmonary function was calculated using a formula described previously. ¹⁴ The calculation was based on the number of segments that remained after surgery out of 42 pulmonary segments. If a patient has atelectasis and/or bronchial obstruction, the standardized pulmonary functional loss ratio was calculated after excluding the number of the sub segments obstructed by tumor in the lobe or lung.

As the standardized pulmonary functional loss ratio, the VC and FEV1 ratios were calculated using the formula:

$$\text{measured postoperative respiratory function}/\text{predicted postoperative respiratory function}.$$

Pathological evaluation

Certified pathologists evaluated the specimens for this study. For all dissected tumors and surgical margins, formalin‐fixed, paraffin‐embedded tissue blocks were sectioned and examined using hematoxylin and eosin staining and immunohistochemistry.

Patient follow‐up

Within 2 months after surgery, patients were followed up with a physical examination, chest x‐ray, computed tomography (CT), and laboratory tests. Although the follow‐up schedule after surgery varied, it usually entailed a chest CT every 3 to 6 months and brain magnetic resonance imaging, bone scintigraphy, and/or positron emission tomography/CT every 6 to 12 months for the first 2 years. This was followed by evaluations every 6 to 12 months. If recurrence was suspected, the follow up schedule was tightened. Postoperative adjuvant chemotherapy was recommended based on the final pathological stage.

Statistics

Groups were compared using Fisher's exact test. Comparisons of functional changes after surgery within each group were made using two‐sample Student's t‐test for paired data. Group data are expressed as means ± standard deviation. Kaplan–Meier analysis was used to estimate 5‐year relapse‐free survival (RFS) and 5‐year OS and the curves were compared using the log‐rank test. Differences between groups were considered significant when p < 0.05. Statistical analyses were performed using JMP IN 15.2.0 software (SAS Institute).

RESULTS

Comparison of the clinical characteristics, pathologic stage, and preoperative treatments between patients receiving sleeve lobectomy or pneumonectomy are summarized in Table 1. There were no significant differences in age, sex, nodal status, or pathological stage between the two groups. Tumor histology, size, and location were slightly differed between the sleeve lobectomy group and pneumonectomy group. The operation time was significantly longer in the sleeve lobectomy than pneumonectomy group (319.44 ± 59.48 min vs. 202.9 ± 57.71 min; p = 0.0004), and the duration of chest drainage was shorter after sleeve lobectomy (9.00 ± 3.43 days vs. 2.27 ± 0.75 days; p < 0.0001). Moreover, the 30‐days operation‐related mortality was significantly lower after sleeve lobectomy (3.2%) than after pneumonectomy (9.6%). The 5‐year RFS rate was 46.67% versus 29.03% in patients with sleeve lobectomy versus pneumonectomy, whereas the 5‐year OS was 63.33% versus 38.71% (Figure 2).

FIGURE 2.

Kaplan–Meier curves for (a) relapse‐free survival and (b) overall survival among patients who underwent sleeve lobectomy (red line) or pneumonectomy (blue line)

Pulmonary function before and after surgery was compared in 20 eligible patients (11 pneumonectomy and 9 sleeve lobectomy) extracted from the two groups. There was no significant between‐group difference in the preoperative VC (pneumonectomy 3404.55 ± 180.68 mL vs. sleeve lobectomy 3768.89 ± 199.75 mL; p = 0.1929) or FEV1 (pneumonectomy 2410 ± 216.31 mL vs. sleeve lobectomy 2648.89 ± 239.14 mL; p = 0.4683). By contrast, both postoperative VC (pneumonectomy 1880 ± 131.74 mL vs. sleeve lobectomy 2597.78 ± 145.64 mL; p = 0.0018) and FEV1 (pneumonectomy 1440.91 ± 114.15 mL vs. sleeve lobectomy 1988.89 ± 126.2 mL; p = 0.0047) were better following sleeve lobectomy (Figure 3). Figure 4 shows the differences in preoperative, predicted postoperative, and actual measured postoperative respiratory function between the two groups. Notably, the VC ratio was better in the pneumonectomy than in the sleeve lobectomy group (1.003 ± 0.117 vs. 0.779 ± 0.12; p = 0.0008). Likewise, the FEV1.0 ratio in the pneumonectomy group was also better than in the sleeve lobectomy group (1.132 ± 0.226 vs. 0.851 ± 0.063; p = 0.0038).

FIGURE 3.

Distribution maps of the preoperative and postoperative (a) vital capacity (VC) and (b) forced expiratory volume in 1 s (FEV1) in patients who underwent pneumonectomy (red line) or sleeve lobectomy (blue line)

FIGURE 4.

Box plots of the preoperative, predicted postoperative, and actual postoperative vital capacity (VC) (a) and forced expiratory volume in 1 s (FEV1) (b) in patients who underwent pneumonectomy (red) or sleeve lobectomy (blue). Shown in (c) are the standardized pulmonary functional loss ratios for VC and FEV1 (measured postoperative respiratory function/predicted postoperative respiratory function × 100). Values are expressed as mean ± standard deviation (SD).

DISCUSSION

In the present study, respiratory function tests showed that postoperative actual measured VC and FEV1 were significantly better preserved after sleeve lobectomy than pneumonectomy. Notably, however, the VC and FEV1 ratios (actual postoperative respiratory function/predicted postoperative respiratory function), which were calculated as standardized pulmonary functional loss ratios, were better in the pneumonectomy group than in the sleeve lobectomy group.

Many surgeons agree that sleeve lobectomy should be considered as the first strategy in any case of NSCLC that can be radically resected with this technique. This is because sleeve lobectomy is associated with better short‐term perioperative outcomes and better OS than pneumonectomy. ⁵ Consistent with those findings, in the present study the 30‐day mortality was significantly lower after sleeve lobectomy (3.2%) than after pneumonectomy (9.6%), indicating that bronchoplasty is a safer technique than leaving main bronchial stumps. Nevertheless, some surgeons are still of the opinion that pneumonectomy is a better course for patients with N1/N2 disease. ² This is in part because the relationship between survival and lymph node status is unclear in patients treated with sleeve lobectomy or pneumonectomy. In addition, three meta‐analyses ² , ³ , ⁵ showed that, although there is a significant difference in 5‐year OS between sleeve lobectomy and pneumonectomy for patients with pN0 or pN1 disease, there is no difference for patients with pN2 or pStage III disease.

In a prospective study carried out to assess pulmonary function following pneumonectomy or sleeve lobectomy, more favorable results were obtained with sleeve lobectomy with regard to preservation of FEV1 (mean perioperative FEV1 loss was 170 ml [range, 0–500 mL] after sleeve lobectomy vs. 620 mL [range, 200–1400 ml] after pneumonectomy, p < 0.0003). ¹⁵ Still, from oncological and surgical viewpoints, pneumonectomy is unavoidable in some cases. Moreover, the VC and FEV1 ratios, which we calculated as the ratio of the measured to the predicted postoperative respiratory function, were better after pneumonectomy than after lobectomy group. Therefore, when pneumonectomy is performed, clinicians should be aware that early and long‐term postoperative pulmonary function may be significantly better than expected. Multiple factors adversely affect operative mortality and cardiopulmonary morbidity after pneumonectomy. ² , ³ , ⁵ , ¹⁶ Although pneumonectomy remains a high‐risk procedure, it still should be considered a treatment option in selected NSCLC patients with sufficient respiratory function. Thoracic surgeons should not hesitate to use radical pneumonectomy if it appears likely to cure a patient's lung cancer.

A beneficial surgical technique that may prevent severe postoperative complications after pneumonectomy is reinforcement of the mainstem bronchus stump using vascularized tissue to prevent a bronchopleural fistula (BPF). ¹⁷ , ¹⁸ A BPF is one of the most serious complications after pulmonary resection and reportedly occurs in ~1.5%–15% of patients after pneumonectomy. ¹⁹ To prevent a bronchopleural fistula, it is recommended that every bronchial stump be covered using omental, muscular, ²⁰ pericardial, ²¹ , ²² or diaphragmatic flaps ²³ whenever one or more of the following risk factors is present: right or completion pneumonectomy, high‐dose radiotherapy, or residual tumor at the bronchial stump. ¹⁷ It is also essential to prevent cardiopulmonary complications during the postoperative period. Improved perioperative management related to anesthesia/critical care (such as early extubation), pulmonary rehabilitation (including aggressive chest physiotherapy, secretion control, and early ambulation with exercise) and multimodal analgesia (including epidural anesthesia, non‐steroidal anti‐inflammatory drugs, and an anticonvulsant drug used to treat neuropathic pain) ²⁴ , ²⁵ have reduced the incidence of potentially fatal cardiopulmonary complications after pneumonectomy. Prevention and attention to complications and better pain management during the early postoperative period is essential to provide further improvement of the respiratory and general condition of patients following pneumonectomy.

The finding that preoperative spirometry is predictive of long‐term survival after a major resection, including pneumonectomy, has not been widely reported. ²⁶

Calculating accurate predicted postoperative pulmonary function is an important factor in determining the appropriate surgical strategy. This is especially true for patients with impaired pulmonary function. Although pneumonectomy may be desirable for its curability, the patient's lung function may not allow it. Several techniques for predicting postoperative pulmonary function have been reported, but most yield a calculated lung function that is lower than the actual postoperative pulmonary function after pneumonectomy. ²⁷ , ²⁸ In theory, atelectasis caused by bronchial obstruction because of a tumor does not change predicted postoperative pulmonary function after sleeve lobectomy. ²⁹ In the present study, however, predicted postoperative FEV1 was lower than the measured FEV1 after sleeve lobectomy. Five cases of each group had atelectasis and/or bronchial obstruction, and they may have been affected by the discrepancy in degree of bronchial obstruction between the predicted and actual values. In cases where selection of the surgical procedure may affect curability, it is necessary to make decisions around surgical procedure with that in mind. A more accurate predictive formula for calculating postoperative predictive pulmonary function will be needed for selection of sleeve lobectomy versus pneumonectomy.

Our study has several potential limitations. The first is the absence of measurements between 1 and 6 months after surgery. As a result, the time course of functional recovery could not be estimated from the present study. The time at which this ratio returns to the predicted value needs to be clarified through future study. An important second imitation is the small sample size and possible selection and allocation bias, which are the main pitfalls of comparison studies.

In summary, the VC and FEV1 ratios, calculated as the ratio of the measured to the predicted postoperative pulmonary function, was better after pneumonectomy than sleeve lobectomy. This means that postoperative respiratory function may be better than expected, even after pneumonectomy. Although pneumonectomy remains a high‐risk procedure with severe complications and high mortality, it still should be considered a treatment option in selected thoracic disease patients who have sufficient respiratory reserves and whose general condition permits it.

AUTHOR CONTRIBUTIONS

All authors had full access to the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: K.I. Acquisition of data: T.M., S.T., N.K., S.K., H.I., K.T., and H.S. Analysis and interpretation of the data: T.M., and K.I. Drafting of the manuscript: T.M., and K.I. Critical revision of the manuscript for important intellectual content: K.I. Statistical analysis: K.N. Study supervision: Y.M.

CONFLICT OF INTEREST STATEMENT

The authors have no conflict of interest.

Matsuo T, Imai K, Takashima S, Kurihara N, Kuriyama S, Iwai H, et al. Outcomes and pulmonary function after sleeve lobectomy compared with pneumonectomy in patients with non–small cell lung cancer. Thorac Cancer. 2023;14(9):827–833. 10.1111/1759-7714.14813