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Ann Thorac Surg 2003;76:1796-1801
© 2003 The Society of Thoracic Surgeons

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Original article: general thoracic

Lung resection for non–small-cell lung cancer in patients older than 70: mortality, morbidity, and late survival compared with the general population

^a Department of Cardiothoracic Surgery, Erasmus Medical Center Rotterdam, Rotterdam, Netherlands
^b Department of Public Health, Erasmus Medical Center Rotterdam, Rotterdam, Netherlands

Accepted for publication June 13, 2003.

^* Address reprint requests to Dr Kappetein, Department of Cardiothoracic Surgery, Room BD 156, Erasmus MC, PO Box 2040, 3000 CA Rotterdam, Netherlands.
e-mail: a.kappetein{at}erasmusmc.nl

	Abstract

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BACKGROUND: Operative mortality and morbidity in elderly patients operated on for non–small-cell lung cancer are acceptable. However, risk factors for hospital mortality and the benefits for the patients in the long term are insufficiently defined, and survival compared with the general population is not known.

METHODS: From January 1989 to October 2001, 126 consecutive patients older than 70 years of age underwent resection for non–small-cell lung cancer. Each patient was scaled according to the Charlson Comorbidity Index. Postoperative events were divided into minor and major complications. Risk factors for complications and long-term survival were assessed by univariate and multivariate logistic regression analysis. Survival was compared with the yearly expected survival rates of the general population.

RESULTS: The hospital mortality was 3.2%. Minor complications occurred in 71 (57%) patients, major complications, in 16 (13%) patients. No risk factor was predictive for major complications. However, a Charlson comorbidity grade of 3 to 4 was predictive for major complications (odds ratio, 12.6; 95% confidence interval, 1.5 to 108.6). Our study showed a 5- and 10-year survival rate of 37% (95% confidence interval, 23 to 51) and 15% (95% confidence interval, 8 to 22). Smoking (odds ratio, 2.3), chronic obstructive pulmonary disease (odds ratio, 2.1), and pathologic stage IIIA (odds ratio, 2.2) or IIIB (odds ratio, 11.9) were risk factors for long-term survival. The observed survival was lower than the expected survival, but the difference decreased with increasing time after pulmonary resection.

CONCLUSIONS: Pulmonary resection for non–small-cell lung cancer in patients older than 70 years shows acceptable morbidity and mortality. The Charlson index is a better predictor of complications than individual risk factors. In time survival is no longer correlated with the disease but follows the same pattern as the general population.

	Introduction

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The incidence of lung cancer in men in the Netherlands has decreased from 109 per 100,000 per year in 1989 to 1991 to 93 per 100,000 per year in 1995 to 1997, whereas in women the incidence has increased from 18 to 23 per 100,000 per year. Lung cancer mortality in men has decreased from 106 to 91 per 100,000 per year and has increased in women from 15 to 20 per 100,000 per year [1]. There is a general trend worldwide of an increasing lung cancer incidence of the elderly population as well as the proportion of patients with serious comorbidity.

Resection still represents the main curative treatment modality for patients with non–small-cell lung cancer. The risk of operation is higher in patients with concomitant respiratory or cardiac disease [2–4]. Recent data suggest that the operative mortality rate in the elderly is acceptable [2, 5–9]. However, the benefits for the patients in the long term are less well defined, and survival compared with the general population is not known.

The aim of this study is to assess the early morbidity and mortality and the late survival of elderly patients operated on for non–small-cell lung cancer, to identify risk factors, and to compare the long-term results with the survival of the general population stratified according to age and sex.

	Material and methods

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Data collection
Clinical data were obtained from the medical records. All electrocardiograms were evaluated for signs of myocardial infarction, left ventricular hypertrophy and arrhythmias. Follow-up was completed in all patients through February 2002. Patients were followed up with regular visits to the outpatient clinic. Civil administrations provided the date of death; the cause of death was obtained from the general practitioner in case of out-of-hospital death. The following risk factors were evaluated: sex, type of surgery, histologic cell type, pathologic stage, smoking habits, diabetes, coronary artery disease, forced expiratory volume in 1 second (unknown in 17 patients), and chronic obstructive pulmonary disease. All patients who used oral bronchodilators were considered as having chronic obstructive pulmonary disease. Each patient was scaled on the Charlson Comorbidity Index (CCI) [10], a weighted index of 19 conditions found to significantly influence survival in cancer patients and given a score based on the relative mortality risk. The score can be divided into four comorbidity grades: 0, 1 to 2, 3 to 4, and 5 or more. Patients were considered to have a comorbid condition if a listed disorder was mentioned in the records or if the patient was treated for it. Cardiac disease is associated with a higher risk of operation in patients with lung cancer [2–4, 11, 12]. Therefore, we modified the CCI by scoring all forms of coronary artery disease (myocardial infarction, angina, coronary artery bypass grafting, and percutaneous transluminal coronary angioplasty) with a value of 1.

Histologic typing occurred according to The World Health Organization Histologic Typing of Lung Tumors [13]. The postsurgical (pathologic) stages of the patients were determined according to the international TNM classification for lung cancer [14].

Hospital mortality included all deaths during the first 30 days, or during the postoperative hospital stay. Complications were classified as minor (non–life-threatening) or major (potentially life-threatening), occurring within 30 days of surgery, or within 3 months in case of empyema or bronchopleural fistula [15]. Patients having both minor and major postoperative complications were coded as having major complications only, although the nature of the minor complication was also recorded.

Patients
Between January 1, 1989, and October 31, 2001, 126 patients (101 men, 25 women), who were 70 years or older, underwent pulmonary resection for non–small-cell lung cancer at the Department of Cardio-Thoracic Surgery of the Erasmus Medical Center, Rotterdam. Three men and 2 women underwent surgery at different time intervals for a second tumor or a tumor recurrence. One woman left the country and was lost to follow-up; 125 patients who were operated on were included in this study. The mean age at time of surgery was 74 years (range, 70 to 82 years); 7 patients were octogenarians.

Data analysis
Univariate logistic regression analysis was used to discriminate independent risk factors for major complications after surgical resection. Long-term survival curve was estimated by the Kaplan-Meier method; 5 and 10-year survival are expressed as percentage ± 95% confidence intervals (CI). Cox proportional hazard analysis was used to determine risk factors for long-term survival. Both the logistic and Cox proportional multivariate analyses were performed with a stepwise forward regression model in which each variable with a p value of less than 0.1 in the univariate analysis was entered in the model.

Yearly expected survival rates for the 125 patients were calculated from age-specific and sex-specific mortality data of the Dutch general population. The age was updated annually, correcting for withdrawals during follow-up. Poisson regression was used to test whether there was a difference between the observed (including hospital deaths) and expected survival rates, and a rate ratio (or relative risk) was estimated. To test whether this difference changed with time since pulmonary resection, time was entered into the Poisson model as a linear continuous variable. The resulting estimate has the interpretation of decrease of the rate ratio per additional year of follow-up.

	Results

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A history of myocardial infarction was present in 22% of this study group. None of these patients underwent lung resection within 6 months after infarction. Six patients had undergone a prior coronary artery bypass surgery; 2 patients underwent coronary artery bypass surgery and lobectomy in one session. Left ventricular hypertrophy was diagnosed in 16% and atrial fibrillation in 5% (Table 1).

The prevalence of comorbid conditions of the CCI is listed in Table 2. Charlson Comorbidity Index was 0 in 25 patients, 1 in 42, 2 in 29, 3 in 24, 4 in 5, and 5 or more in none (Table 1). Operative characteristics are listed in Table 3.

Complications
Complications occurred in 58%. Minor complications occurred in 71 patients (57%). The most common complications were arrhythmia (31%) and air leak lasting more than 5 days (21%). Major complications occurred in 16 patients (13%; Table 4). None of the female patients experienced a major complication. This study showed a postoperative myocardial infarction rate of 1.6% (2 cases). In one of the 27 cases with a history of myocardial infarction, a reinfarction was noted (reinfarction rate of 3.7%). The second case of infarction postoperatively led to death 2 days after surgery.

To determine the difference in survival between patients operated on for non–small-cell lung cancer and the general population we compared the survival of the present series (observed) to the expected survival of the elderly general population (70 years or older) in the Netherlands (Fig 1). The observed survival was significantly (p < 0.001) lower than the expected survival, but the difference significantly (p = 0.01) decreased with increasing time after pulmonary resection.

View larger version (19K): [in this window] [in a new window]   Fig 1. Expected versus observed survival, with 95% confidence limits (postoperative deaths included).

	Comment

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Studies indicate that patients undergoing major noncardiac surgery within 3 months of a myocardial infarction have a high reinfarction rate of up to 37%, whereas patients undergoing major noncardiac surgery more than 6 months after a myocardial infarction have a lower reinfarction rate of approximately 5% [17]. Our results (reinfarction rate of 3.7%) confirm that patients can safely undergo a pulmonary resection 6 months after a myocardial infarction. It is not certain that with current interventional cardiology techniques surgery has to be delayed until 6 months after a myocardial infarction.

It is well known that pneumonectomy, especially right-sided pneumonectomy, is associated with higher incidence of complications when compared with limited resections [15, 18], and higher mortality rates in some series can partly be explained by the higher percentage of pneumonectomies [5, 7, 8, 18]. The British Thoracic Society [3] noted that pneumonectomy is associated with a higher mortality risk in the elderly and that age should be a factor in deciding suitability for pneumonectomy. However, Ginsberg and colleagues [6] reported a lower mortality rate in pneumonectomies in elderly patients (5.9%) compared with lobectomies (7.3%). Also in our series no mortality was observed in the pneumonectomy group, and this procedure was also not associated with a higher incidence of major complications. Patient selection is the most suitable reason for this observation. No individual risk factor was significantly predictive for major postoperative complications. However, as we also showed in an earlier series [19], the CCI, a morbidity index score, was correlated with a higher risk for major postoperative complications.

The operative mortality rate of 3.2% is well within the range published by other investigators, who reported a hospital mortality ranging from 1.2% to 12.8% [2, 5–9, 16] (Table 7). It is also comparable to the mortality rates of lung cancer resection in the population younger than 70 years [2, 5, 7, 9, 16]. The low mortality rate of 1.2% in the series of Morandi and colleagues [9] can partly be explained by excluding patients who underwent surgery after neoadjuvant chemotherapy. Because of the exclusion of these patients, who most probably represent a group with advanced stage non–small-cell lung cancer, a selection bias is introduced.

Older age at operation is described as a risk factor with regard to late survival. Our study shows a 5-year survival rate of 37%. Other investigators noted a 5-year survival rate ranging from 28% to 48% [2, 5, 8, 9] (Table 6). Roxburgh and colleagues [7] reported a 4-year survival of 67%. This high survival rate can be attributed to a strict selection protocol and the fact that postoperative deaths were excluded. The difference in survival between the patients and the general Dutch population significantly decreases with time, which indicates that with time survival is no longer correlated with the disease but follows the same pattern as for the general population.

The limitation of this study is that it is retrospective in design, and in 17 patients data on forced expiratory volume in 1 second, and in 2, data on pathologic stage, were missing.

We conclude that pulmonary resection for non–small-cell lung carcinoma is justified in patients older than 70 years; its morbidity, mortality, and survival are acceptable. The CCI is a better predictor of major postoperative complications than individual risk factors. Despite a certain frequency of minor and major complications, patients older than 70 years can be operated on with a good survival irrespective of the type and extent of resection. In time, survival is no longer correlated with the disease but follows the same pattern as the general population.

	References

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