Approximately 80% of patients with lung cancer are diagnosed with locally advanced or metastatic disease1 and cannot be offered curative treatment.2,3 It has been estimated that 20% to 30% of patients with lung cancer develop central airway obstruction, causing varying degrees of dyspnea, atelectasis, postobstructive pneumonia, respiratory failure, or death.4,5 Central airway obstruction can sometimes quite rapidly cause respiratory distress, leading to acute hospital admission for immediate bronchoscopic management.6,7 Interventional endoscopic procedures can provide immediate symptom relief and improve lung function.8
The choice of procedure depends on the type of obstruction and the available resources and expertise.9 Intraluminal lesions may be amenable to treatment with laser ablation, electrocautery, or debulking with a rigid bronchoscope. External compression of the airway often requires airway stenting, whereas mixed lesions frequently require a combination of different techniques. Preoperative evaluation with a recent computed tomography thorax and bronchoscopy is necessary to assess the type of lesion, the pulmonary circulation, and the patency of the airways distal to the tumor.6
Bronchoscopic procedures can effectively alleviate dyspnea, stop hemoptysis, and improve the quality of life in patients with lung cancer.10,11 Interventional bronchoscopy was introduced at the Interventional Centre, Rikshospitalet, in 1998. Laser ablation, electrocautery, and silicone and metal stents have been offered at our institution as part of the palliative treatment of patients with lung cancer. Rikshospitalet is a tertiary center and patients with malignant airway obstruction have been referred to us for treatment from all of the other hospitals in Norway.
Studies on survival after endoscopic interventions in malignant airway obstruction are limited in number. The largest study to date was published by Cavaliere et al in 1996.1 Reports on survival in recent years have been on smaller subsets of patients. We report our experience of the first 10 years of interventional bronchoscopy in malignant airway obstruction with regard to complications and survival.
PATIENTS AND METHODS
All patients referred for interventional bronchoscopy were evaluated on the basis of medical history, clinical examination, a recent computed tomography thorax, and bronchoscopy. The patients who were assessed as being likely to have a life expectancy of more than 3 weeks, without severely compromised pulmonary circulation and with patent airways distal to the stenosis, were accepted for treatment. The life expectancy assessment was based on the opinion of the referring pulmonologist or oncologist, and was discussed with the interventional pulmonologists at our institution. A good performance score was considered preferable, but some patients with a poor performance score (Eastern Cooperative Oncology Group 3 or 4) were accepted for treatment when the poor performance was considered to be caused by a central airway obstruction.
Between 1998 and 2009, 257 patients with malignant airway obstruction were treated with interventional bronchoscopy at our clinic. The group consisted of 167 men and 90 women (median age 67, range: 31 to 88 y, Table 1). Patients with endobronchial carcinoids and adenoid cystic carcinomas were not included in the analysis as the prognosis in these 2 groups is known to be markedly different.
All patients were consecutively registered in the department's clinical database. Sex, age, treatment modality, complications, duration of the procedure, and dates of intervention were prospectively registered as a part of the department's routine. Additional data such as histology of the tumor, oxygen dependency, and information regarding the postoperative period were retrospectively collected from the medical charts. Time of death was registered based on information from the National Population Register of Norway.
Survival was compared between patients with primary lung versus metastatic cancer to the airways and between patients with different histological types of cancer, such as small-cell lung cancer (SCLC), nonsmall-cell lung cancer (NSCLC), and metastatic cancer.
The bronchoscopic procedures were performed by interventional pulmonologists in the operating room setting.
The procedures were performed under general anesthesia. Propofol was used for sedation (4 to 8 mg/kg/h) and remifentanil for analgesia (0.1 to 0.5 μg/kg/min). Cisatracurium was used for the induction of neuromuscular blockade at a dosage of 0.15 mg/kg, and for prolonged neuromuscular blockade, if needed, by a further infusion of 0.2 mg/kg/h. All of the patients were ventilated using a closed circuit connected to the ventilator. Respiration was maintained at a rate of 10 to 15 breaths/min with a peak pressure of less than 30 mm Hg. The proportion of oxygen in the anesthetic gas mix was 0.3 to 0.9 when thermal modalities were not used, and 0.35±0.05 during laser ablation.
Most procedures were performed using a flexible bronchoscope through an endotracheal tube. In patients with large tumor masses, a rigid bronchoscope was used for tumor debulking or silicone stent insertion. Lesions with intraluminal growths were treated using a neodymium: yttrium aluminium garnet laser or electrocautery. The laser was set to 40 to 45 W and 1 second of laser treatment was followed by a 1-second interval to avoid overheating and combustion of the tumor. Extrinsic compression from tumors or enlarged lymph nodes was treated with metallic (Ultraflex) or silicone stents (Dumon, Hood). A combination of different techniques was used when deemed indicated by the physician.
Survival after the first interventional bronchoscopy treatment was reviewed. The data are presented as median with interquartile range. Survival time was calculated from the date of the first procedure to the date of death. The end of study was set at September 1, 2009. The survival time was estimated using Kaplan-Meier and Cox regression methods. The log-rank test was performed to compare the results between groups. A 2-tailed P value of less than 0.05 was considered statistically significant.
The study was approved by The Norwegian Regional Ethics Committee and the Norwegian Social and Health Directorate.
Among the 257 patients, 210 had primary lung cancer and 47 had lesions metastatic to the airway; 11 histological groups were represented (Table 2). The tumor was localized in the trachea in 56 patients, and was localized in the bronchi of the right and left lung in 138 and 84 patients, respectively. The tumor compromised more than 1 airway in 21 patients (Fig. 1). The median time from the date of diagnosis to interventional bronchoscopy was 3 months (range: 0 to 70). The median time from diagnosis to interventional bronchoscopy in patients with SCLC was 9 months (range: 0 to 60), whereas in patients with NSCLC it was 3 months (range: 0 to 70) (P=0.02).
A total of 360 endobronchial interventions were performed in 257 patients, ranging from 1 to 8 procedures per patient (Table 1). The number of procedures performed per patient was not significantly different between the groups. Rigid bronchoscopy was performed in 43 procedures, and flexible bronchoscopy in 317. Subsequent interventions were performed due to recurrence of the airway obstruction.
By the end of the study, 239 of the patients had died, and 18 were still alive. Eighteen patients died within 2 weeks after the procedure. Eight of these patients received endoscopic interventions because they were in danger of immediate suffocation, thus they were accepted for bronchoscopic intervention, even though their life expectancy was limited. Ten patients died within the first 2 weeks after the procedure, even though their life expectancy had been preoperatively assessed as being longer than 3 weeks. Five of these patients died in the hospital within a few days of the procedure. The remaining 5 patients unexpectedly died at home of unknown causes.
Patients in all performance scores were treated. Nineteen patients were admitted as emergency cases and 31 had critical airway stenosis, defined as imminent tracheal or bilateral main bronchus occlusion. Sixty-seven patients (32%) were oxygen dependent; 52 of them were discharged without oxygen. Four patients were on mechanical ventilation before the procedure; 3 of them were discharged after treatment.
In the primary lung cancer group, the median survival after interventional bronchoscopy was 15 weeks, whereas in the metastatic cancer group it was 18 weeks (P=0.35, Fig. 2, Table 3). Patients with SCLC (n=18, 8.6%) had a shorter life expectancy after interventional bronchoscopy compared with the NSCLC group (7 and 17 wk, respectively, P=0.04).
The following complications of the procedures were observed: 1 pneumothorax (0.3%), 1 case of life-threatening airway obstruction during the procedure (0.3%), and 5 cases of serious hemorrhage that required the procedure to be interrupted (1.4%). All cases of serious hemorrhage occurred in patients with lung metastases from renal carcinoma. The bleeding was managed by applying local pressure at the bleeding site with the rigid bronchoscope and instillation of cold saline, adrenaline, or tranexamic acid. The endoscopic interventions were resumed after successful hemostasis and completed as planned in 4 cases. One patient with renal failure, renal cancer, and lung metastases died on the operating table from profuse bleeding during his eighth procedure.
Median survival in the patients with primary lung and metastatic cancer in this study was 15 weeks (110 d). This result corresponds to the data reported by some other researchers (15 wk in a study by Cavaliere et al1 and 16 wk in a study by Suh et al12). Eighteen of our patients (6%) died within the first 2 weeks after the procedure. None of these early deaths was considered to be related to the interventional procedure. In a study of survival after stent insertion for malignant airway stenosis, Breitenbucher et al13 reported a similar number of early deaths, as 3.5% of their patients did not survive the first week after stent insertion. In our 8 patients who died within 2 weeks, the interventional procedure (stenting in 7 out of 8) was performed to avoid suffocation and was carried out even though their life expectancy was recognized as being limited. Disease severity was underestimated in some of the remaining 10 patients, but some of these early deaths were unexpected, even in retrospect. Moreover, they illustrate the fact that the assessment of life expectancy is not simple in patients with malignancies. Despite this, there seems to have been a learning curve for the preoperative assessment: 8 of these early deaths occurred within the first 6 years after the introduction of interventional bronchoscopy at our institution, and only 2 early deaths occurred within the last 5 years.
The majority of our patients had lesions that obstructed the trachea or the main stem bronchi (Fig. 1). In general, bronchoscopic interventional procedures are mostly useful down to the lobar level, as it is technically more difficult to perform procedures in the smaller bronchi. The benefit with regard to oxygenation and ventilation is also less.
Metastatic disease is, by definition, a widespread disease and pulmonologists and patients alike assume a poor prognosis. However, we found no significant difference in the survival of these patients compared with the primary lung cancer group, and we suggest that even patients with metastatic disease should be considered candidates for interventional endoscopic procedures. Central airway obstruction can be difficult to detect, even for pulmonologists, and as patients with malignancies other than lung cancer are usually treated by nonpulmonologists, we suspect that many patients with metastatic disease may have undetected central airway obstruction. Consequently, we believe that many patients with metastatic disease are not offered interventional bronchoscopy, even though such treatment could achieve effective palliation. In the largest cohort study published by Cavaliere et al,1 which included 1838 patients referred for endoscopic treatment of malignant airway obstruction, only 130 patients (7%) had metastatic disease. In our study, 16% had lung metastases from other malignancies.
Patients with newly diagnosed SCLC were generally not referred for early intervention due to the good initial sensitivity to chemotherapy. However, 2 groups of patients with SCLC did receive endoscopic treatment. The first group included the 4 patients who were diagnosed with a critical central airway stenosis and risked early death before chemotherapy could be effective. The second group included the 14 who had a slow disease progression after chemotherapy and recurrence. As a consequence, our patients with SCLC were highly selected among the general population of patients with small cell lung cancer.
Interventional bronchoscopy is generally considered to be safe, with a complication rate as low as 1% (0% to 2.2%) in the hands of an experienced operator, but some complications do occur.14 The most common are bleeding and difficulties in maintaining adequate ventilation.8 In our practice, serious complications were rare (1.9% of all procedures), and only one of them resulted in the death of a patient (0.3%). This patient, who had a highly vascularized lung metastasis from renal cancer in the right main bronchus, also had renal failure, and died of profuse bleeding during his eighth procedure. Endoscopic yttrium aluminium garnet laser resection and mechanical debulking with a rigid bronchoscope every 2 to 3 months prevented this patient from suffocation and prolonged his life for 1.5 years. Ernst et al15 reported a 20% complication rate in a multicenter study of therapeutic bronchoscopic procedures, but they included a wider range of less serious complications, such as episodes of desaturation below 90% and transient hypotension, in their data.
Even though the complications might be serious, it is our conviction that patients with terminal cancer (facing death from suffocation) should be offered treatment. Interventional bronchoscopy in these patients must be performed by an experienced team of pulmonologists, anesthesiologists, and operating room staff.
Interventional endoscopic procedures have an almost immediate effect, which is important in patients with malignant airway obstruction as their life expectancy is short. Careful preoperative evaluation is important for patient selection, but the assessment of life expectancy can be difficult. The procedures are safe and complications are rare, but the high incidence of hemorrhaging in the patients with metastases from renal carcinoma calls for caution in these patients. Patients with lung metastases from other malignancies survive as long as patients with primary lung cancer and should be offered treatment.
The authors thank Landsforeningen for Hjerte-og Lungesyke, Helse-og Rehabilitering (LHL), Norway, for financial support of this project.
1. Cavaliere S, Venuta F, Foccoli P, et al. Endoscopic treatment of malignant airway obstructions in 2,008 patients Chest.. 1996;110:1536–1542
2. Rostad H, Naalsund A, Jacobsen R, et al. Small cell lung cancer in Norway. Should more patients have been offered surgical therapy? Eur J Cardiothorac Surg. 2004;26:782–786
3. Rostad H, Strand TE, Naalsund A, et al. Lung cancer surgery: the first 60 days. A population-based study Eur J Cardiothorac Surg. 2006;29:824–828
4. Wood DE, Liu YH, Vallieres E, et al. Airway stenting for malignant and benign tracheobronchial stenosis Ann Thorac Surg. 2003;76:167–172
5. Asimakopoulos G, Beeson J, Evans J, et al. Cryosurgery for malignant endobronchial tumors: analysis of outcome Chest. 2005;127:2007–2014
6. Ernst A, Feller-Kopman D, Becker HD, et al. Central airway obstruction Am J Resp Crit Care Med. 2004;169:1278–1297
7. Noppen M, Poppe K, D'Haese J, et al. Interventional bronchoscopy for treatment of tracheal obstruction secondary to benign or malignant thyroid disease Chest. 2004;125:723–730
8. Bolliger CT, Sutedja TG, Strausz J, et al. Therapeutic bronchoscopy with immediate effect: laser, electrocautery, argon plasma coagulation and stents Eur Respir J. 2006;27:1258–1271
9. Chhajed P, Somandin S, Baty F, et al. Therapeutic bronchoscopy for malignant airway stenoses: Choice of modality and survival J Cancer Res Ther. 2010;6:204–209
10. Saji H, Furukawa K, Tsutsui H, et al. Outcomes of airway stenting for advanced lung cancer with central airway obstruction Interact Cardiovasc Thoracic Surg. 2010;11:425–428
11. Amjadi K, Voduc N, Cruysberghs Y, et al. Impact of interventional bronchoscopy on quality of life in malignant airway obstruction Respiration. 2008;76:421–428
12. Suh JH, Dass KK, Pagliaccio L, et al. Endobronchial radiation therapy with or without neodymium yttrium aluminum garnet laser resection for managing malignant airway obstruction Cancer. 1994;73:2583–2588
13. Breitenbucher A, Chhajed PN, Brutsche MH, et al. Long-term follow-up and survival after Ultraflex stent insertion in the management of complex malignant airway stenoses Respiration. 2008;75:443–449
14. Folch E, Mehta AC. Airway interventions in the tracheobronchial tree. Seminars in Respiratory and Critical Care Medicine 2008 Respiration.. 2008;l:441–452
15. Ernst A, Simoff M, Ost D, et al. Prospective risk-adjusted morbidity and mortality outcome analysis after therapeutic bronchoscopic procedures: results of a multi-institutional outcomes database Chest.. 2008;134:514–519
© 2011 Lippincott Williams & Wilkins, Inc.