Interact CardioVasc Thorac Surg 2009;9:260-264. doi:10.1510/icvts.2008.194456
© 2009 European Association of Cardio-Thoracic Surgery
Institutional report - Pulmonary |
Pneumonectomy for bronchogenic carcinoma: analysis of factors predicting short- and long-term outcome
Eelco J. Veena,*,
Maryska L.G. Janssen-Heijnenb,
Ewan D. Ritchiea,
Bonne Biesmac,
Marco P.H. van den Bogartd and
Robert Jan Bolhuisa
a Department of Surgery, Jeroen Bosch Hospital, 's Hertogenbosch, The Netherlands
b Department of Research, Eindhoven Cancer Registry, Eindhoven, The Netherlands
c Department of Pulmonology, Jeroen Bosch Hospital, 's Hertogenbosch, The Netherlands
d Department of Pulmonology, Bernhoven Hospital, Oss, The Netherlands
Received 14 September 2008;
received in revised form 30 March 2009;
accepted 31 March 2009
 Presented at the 16th European Conference on General Thoracic Surgery, Bologna, Italy, June 8–11, 2008.
*Corresponding author. Amphia Hospital, location Molengracht, 4818 CK, Breda, The Netherlands. Tel.: +31-76-5951151; fax: +31-76-5953818.
E-mail address: eveen{at}amphia.nl (E.J. Veen).
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Abstract
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The objective of this study was to analyse predictive factors for postoperative and long-term outcome after pneumonectomy. From 1 January 2000 to 1 January 2005 a total of 91 (31%) pneumonectomies were performed. Multivariable analysis for postoperative morbidity, mortality, and long-term survival was performed. Patients over 70 years had 1.5 times higher risk of dying (HR=1.5, 95% CI=1.1–2.0) within five years compared to younger patients, those with co-morbidity had 1.8 times higher risk compared to no co-morbidity (HR=1.8, 95% CI=1.3–2.7) and those with stage IIIA had 2.3 times higher risk of dying compared to stage I (HR=2.3, 95% CI=1.5–3.6). Overall postoperative mortality within 30 days in patients undergoing pneumonectomy was 10% (n=9). Most patients who died postoperatively were 70 years or older, had cardiovascular comorbidity and underwent right-sided pneumonectomy (n=6). Patients over 70 years had three times higher risk of complications compared to younger patients (OR=3.1, 95% CI=1.1–8.2), and patients undergoing right-sided pneumonectomy had 2.4 times higher risk compared to left-sided pneumonectomy (OR=2.4, 95% CI=0.9–6.4). Pneumonectomy is accompanied by high postoperative mortality and morbidity rates, the highest risk in patients over 70 years and right-sided pneumonectomy, and consequently should lead to meticulous patient selection and perioperative care.
Key Words: Pneumonectomy; Outcome measurement; Non-small cell lung cancer
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1. Introduction
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Complete surgical resection for patients with non-small cell lung cancer remains the only potential curative option. Due to functional status and co-morbidity, only 30% are eligible for surgery, and anatomic lobectomy or pneumonectomy with mediastinal lymh node dissection has been the treatment of choice. The surgical discussion on pneumonectomy has concentrated on postoperative morbidity/mortality rates and its possible impact on long-term survival with conflicting evidence [1–3]. Various studies have identified risk factors influencing postoperative outcome after pneumonectomy [4, 5]. Increased operative risk should be balanced against possible survival benefits, and alternatives such as bronchoplastic procedures should be considered. A proper selection of surgical candidates is crucial in optimizing surgical care and quality of life. In the Netherlands, as in many other countries, current practice emphasises quality assurance and improvement of health care. We analysed predictive factors for postoperative and long-term outcome after pneumonectomy, to be used in the discussion for measuring quality of care and for choosing optimal treatment strategy.
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2. Patients and methods
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From 1 January 2000 to 1 January 2005, 1063 patients were diagnosed with non-small cell lung cancer in two large general hospitals (Jeroen Bosch Hospital in Den Bosch and Bernhoven in Veghel and Oss). Two hundred and ninety-seven patients (28%) were operated on, of whom 91 patients underwent pneumonectomy. Preoperative evaluation and work-up was performed by the pulmonologist, consisting of a chest roentgenogram, ECG, pulmonary function test, CT-scan of chest and abdomen, bronchoscopy, cervical mediastinoscopy or anterior mediastinotomy on indication, and from 2003 onwards a PET scan was performed routinely. Decision in performing pneumonectomy (and therefore not parenchyma saving procedures as e.g. sleeve lobectomy) was made according to the localisation of the tumour at bronchoscopy, centrally localised tumours with hilar pathological lymph nodes and in patients with extensive growth in other lobes.
Preoperatively, a thoracic epidural catheter was routinely inserted. Prophylactic antibiotic therapy was routinely administered; cefuroxim 750 mg. Pneumonectomy was performed through an anterolateral muscle-sparing thoracotomy, with block dissection of hilar nodes and sampling of mediastinal lymph nodes as appropriate. Formal mediastinal lymph node clearance was not performed. All patients were monitored postoperatively for at least 24 h at the intensive care unit. Data were derived from the population-based Eindhoven Cancer Registry. Data on patient and tumour characteristics, treatment and survival were collected directly from the medical records by trained registrars. For this study, additional data for all patients undergoing pneumonectomy (n=91) were collected retrospectively by reviewing the hospital electronic medical files and clinical charts. The following data were available for analysis: age, date of surgery, hospital stay, smoking, ASA classification, neoadjuvant chemotherapy, tumour localisation, respiratory function (FEV1 and TLCO), histology, pTNM Stage, r0 resection, PET scan performed, mediastinoscopy performed and postoperative complications. Type of surgery was classified as pneumonectomy vs. other surgery, which was defined as all parenchyma-saving procedures (lobectomy, sleeve lobectomy, wedge and segmental resections). The definition of a complication developed by the Association of Surgeons of the Netherlands (ASN) was used: ‘Any state or event, unfavourable to the patient's health, which arose during admission or within 30 days after discharge that either causes unintentional injury or requires additional treatment. Complications were categorised as: a) Surgery/intervention-related, b) Infection-related, c) Organ dysfunction (cardiopulmonary – renal – neurological – gastrointestinal), d) Hospital-Provider Errors, and e) Drug-related. Postoperative mortality was defined as death within 30 days of surgery, independent of the cause of death. Co-morbidity was defined as all diseases that were present at the time of cancer diagnosis and classified according to a slightly adapted list of Charlson. Co-morbidity was categorised as 0, 1, and 2 or more additional diseases. Follow-up was performed by the pulmonologist, every three months the first year, every six months the second year and yearly thereafter. Vital status was completed up to 1 January 2006 through linkage with the municipal personal records. Survival time was defined as the time from diagnosis until death or until the last follow-up. In case of obscurity of the patient's health status, the general practitioner was contacted.
2.1. Statistics
For patients diagnosed with stage I–IIIA long-term survival was estimated. Survival differences between patients undergoing pneumonectomy and those undergoing another type of lung surgery were performed with the log-rank test. In a multivariable Cox regression analysis the independent prognostic effects of gender, age, localisation, tumour stage, type of surgery (pneumonectomy vs. other lung surgery) and co-morbidity was evaluated. For patients undergoing pneumonectomy the univariate association between ASA classification, age, localisation, gender, tumour stage, neo-adjuvant chemotherapy and Ro resection on the one hand and postoperative mortality and morbidity on the other hand were tested for statistical significance with the Fisher exact test. Multivariable analysis for postoperative morbidity was performed with the logistic regression model; only variables significantly predicting outcome in the univariate analyses were included in the model (P<0.10). No multivariable analysis was performed for postoperative mortality, because the number of events was only nine. The statistical package SAS was used for all analyses.
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3. Results
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Table 1 summarizes the characteristics of the 91 patients who underwent a pneumonectomy. Three patients were classified as stage 4 as in these patients two carcinomas (primary tumour with metastasis) were localized in different lobes. In stage 1 there were three patients who received neo-adjuvant chemotherapy and were re-staged after resection as stage 1. Patients undergoing pneumonectomy (stage I–IIIA) had a one-year survival rate of 79%, compared to 85% for patients undergoing other surgery; 5-year survival was 46% and 40%, respectively (Fig. 1). Median survival time was 33 months; 53 (58%) patients had died. In multivariable analysis for patients undergoing surgery, risk of dying was almost twice as high for patients with co-morbidity (HR=1.8, 95% CI=1.3–2.7), 1.5 times higher for patients aged 70 years or older (HR=1.5, 95% CI=1.1–2.0) and 2.3 times higher for patients with stage IIIa compared to those with stage 1 (HR=2.3, 95% CI=1.5–3.6). The most common cause of death was lung cancer related (n=30/56%). Six patients died due to cardiovascular events (ruptured aneurysm (n=1), cerebrovascular event (n=1), cardiac failure (n=4). One patient developed a late bronchopleural fistula. In six patients the cause of death was unknown, without signs of local recurrence. Overall postoperative mortality within 30 days for patients undergoing pneumonectomy was 10% (n=9). Table 2 shows the characteristics of the nine patients who died postoperatively, all died due to cardiac or respiratory failure. Furthermore, eight of nine patients who died postoperatively were 70 years or older, six of nine underwent right-sided pneumonectomy and eight of nine were ASA two or three. In one patient on day 2 post-pulmonary oedema occurred and the patient died due to respiratory failure at day 11. Two patients developed respiratory failure/ARDS (acute respiratory distress failure) at day 2 and 3, respectively, suggesting post-pulmonary oedema, however, not described in the medical file. A total of 82 complications were documented in 40 (44%) patients (Table 3), most frequently cardiovascular and/or pulmonary related (n=40/49%). In 11 patients, arrhythmias occurred in the postoperative course, seven after left-sided and four after right-sided pneumonectomy. In the multivariable logistic regression model patients aged over 70 years had a three times higher risk of morbidity compared to younger patients (OR=3.1, 95% CI=1.1–8.2), and patients undergoing right-sided pneumonectomy had a 2.4 times higher risk compared to left-sided pneumonectomy (OR=2.4, 95% CI=0.9–6.4).
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Fig. 1. Survival curves for patients undergoing pneumonectomy and other type of pulmonary surgery for bronchogenic carcinoma. Other type of surgery included all patients in which a lobectomy, sleeve resection, segmentectomy or wedge resection was performed.
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4. Discussion
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Lung cancer often requires extensive resections such as pneumonectomy, with high complication rates resulting in significant morbidity and postoperative mortality. Considerable variability for these outcome measures has been reported, but direct comparison is hampered by different definitions and selection criteria. Postoperative mortality in our series was 10%, which is relatively high but in range with the literature, reporting percentages between 3.3 and 13% (Table 4). In our study, eight of nine patients who died were aged 70 years or older and in six a right-sided pneumonectomy was performed. Several studies confirm these risk factors. The main risk factors identified in literature for postoperative mortality after pneumonectomy were age (>70 years), cardiac disease, lung function (FEV1 <70%/DLCO%) and right-sided pneumonectomy [2–9]. A study by van Meerbeeck et al. observed the highest postoperative mortality risk (17.8%) in patients aged over 70 years who underwent right-sided pneumonectomy, and Simon et al. showed that right-sided pneumonectomy had negative influence on survival [10, 11]. Post-pulmonary oedema is more often seen in patients with right-sided pneumonectomy and could be an explanation for this high risk. The retrospective aspect of our study makes it hard to identify patients with post pulmonary oedema, but in one patient this was mentioned as the cause of death. The prognostic value of reduced preoperative FEV1 appears less well established, as some studies showed an effect on postoperative outcome and survival whereas others found no correlation [2–9]. Ferguson found that the single breath diffusion capacity (DLCO%) is a better predictor of mortality and pulmonary complications than FEV1 [1]. We did not find a relation between pulmonary function and postoperative outcome, which is probably attributable to the retrospective nature of our study and small numbers. Age (>70 years) was the strongest factor influencing postoperative morbidity. Our study shows the postoperative course after pneumonectomy is complicated in almost half the patients. These numbers are in line with those mentioned in literature (Table 4). The reason why patients aged over 70 years do worse after pneumonectomy is still unknown, as for instance in parenchyma saving procedures this association is not found [11, 12]. Leo et al. reported that age per se increased mortality due to the fact that the elderly experienced more respiratory complications. One difference found in comparison with younger patients was the DLCO, which reflects the ageing status of the alveoli-capillary membrane [4]. In the elderly group, respiratory selection criteria should be redefined in our clinic, with the perioperative risk carefully outweighed against gain in survival. Long-term survival for patients with NSCLC undergoing surgery was relatively good and our results do not suggest that this is negatively influenced by pneumonectomy. The extent of resection has been mentioned as a predictor of survival by Alexiou in stage 1 disease (T1 N0 and T2 N), but was not confirmed by Ferguson and Karissson although in their study survival after pneumonectomy was significantly shorter. Predictors for long-term survival in both studies were age, T and N status and male gender [1, 13]. In our group, age (patients >70 years), stage IIIa vs. I and co-morbidity were prognostic factors influencing long-term survival. Twenty-six percent of all patients were resected for stage 1, three patients were re-staged after neo-adjuvant chemotherapy, in three patients pneumonectomy was bronchoscopically the only technical option, in two patients perioperatively performed biopsy of the bronchus showed tumour and sleeve procedure was technically not possible, and most often the tumour grew into the interlobar fissure, one of the pulmonary arteries, or other lobes making parenchyma saving procedures oncological not warranted. Nowadays, multimodality strategies are developed, induction chemo-radiotherapy in lung cancer combined with surgery, which could have a possible negative effect on mortality rates. As our study and literature still show high morbidity and mortality rates after pneumonectomy, emphasis should be put on knowledge of possible risk factors influencing outcome to weigh surgical risk in lung surgery against survival benefit. Although this study has the benefit of using unselected patients in a population-based setting, the retrospective and non-randomized aspect hinders using these outcome data in the discussion for quality control management and risk stratification. So the intention is to start recording our data in real time in the European Society of Thoracic Surgeons registry (https://www.thoracicdata.org/content/index.php). Measuring surgical outcome should be done taking risk adjustments (case mix), real time registry and quality of life into account and should be evaluated in a local audit program resulting in accurate risk stratification and improvement of care [14, 15]. This will hopefully result in finding the optimal balance between surgical risk in pneumonectomy and survival benefits.
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Abstract
1. Introduction
