Predictors of long time survival after lung cancer surgery: A retrospective cohort study

The epidemiology of lung cancer has changed dramatically within the last 40 years. The incidence has increased, especially among women, and there are more adenocarcinomas. The number of surgical candidates in stage I and II disease have increased both for patients below and above 70 years [1–3]. There is an ongoing debate regarding centralisation of lung cancer surgery. Generally, hospitals with low volumes of lung cancer surgery have lower five years survival and more complications than teaching hospitals and hospitals with high volumes [4]. Predictors of higher survival rate or lower complication rate have been female gender [5–10], lower age [5, 6, 8, 9, 11, 12], early preoperative stage [5, 13], lobectomy [5, 9, 12–15], adenocarcinoma [8, 13, 16], no previous coronary heart disease [17–19], and normal pulmonary function tests [6, 9, 11, 17, 20, 21]. Some of these predictors have been analysed only in univariate tests. There are as far as we know no previous reports from county hospitals where lung cancer surgery is performed with staff from larger teaching hospitals.

Aalesund Hospital in Norway is a county hospital with a catchment area of approximately 100 000 inhabitants. The aim of this study was to evaluate lung cancer surgery performed in a county hospital in terms of 30 days mortality, complications and long time survival, and to evaluate predictors of long time survival.

A total of 149 operations in 148 patients at Aalesund Hospital from 1993 to 2006 with non-small cell lung cancer (NCLC) were retrospectively reviewed. One patient had two operations for different lung cancers and only the last operation was included in further analysis. The medical records of two patients were not found and these were excluded from the analysis of complications. The medical records of all patients were followed to 15.09.2007. Mortality data were available for all patients, but details about relapse were missing for four patients. All complications that appeared within 60 days after surgery were registered. Pulmonary embolism and deep venous thrombosis were included when they appeared within 90 days.

After the locally based specialist in thoracic surgery left in 1997, lung cancer surgery was taken over by three specialists from teaching hospitals in Tromsö and Trondheim. Adjuvant cytostatic treatment was introduced in November 2004. Only six patients received adjuvant chemotherapy, 10 patients had adjuvant irradiation therapy. Some advanced stage cases or high risk patients were initially referred to the regional hospital for treatment during the study period, but this was a minority. Pneumectomy was performed when there was a large central tumor or tumor invasion of a main bronchus, and the patients had a good pulmonary function with expected postoperative FEV₁ above 1 litre.

The statistical analysis was performed in SPSS using Chi square tests and Hazard ratio from Cox regression for univariate analysis, and Hazard ratio from Cox regression for multivariate analysis of survival. Variables described as significant in previous studies were included in univariate analyses. All variables in the univariate analyses were included in the multivariate analysis. Kaplan Meier plots were performed to estimate median survival time and to visualize some of the univariate variables.

The Regional Medical Ethics Committee and the Norwegian Social Science Data Service approved the study.

The 30 days mortality rate of 2.7% in this study was comparable or lower than previously reported from high volume hospitals for lung cancer surgery [4, 12]. Five years overall survival rate of 41.6% is comparable to previous reports from larger centres [5, 8, 13]. The higher 30 days mortality and morbidity rate among elderly patients and following pneumonectomy have previously been described [7, 11, 12], but the relation have not been significant in all studies [19]. The early complication rate is prone to information bias in a retrospective study, but our report of 36.3% with ≥ 1 complication was within the same range as in previous reports [4, 7, 12, 13].

Age above 70 years and a more advanced preoperative stage were predictors of reduced long time survival in this study as well as in some previous studies [5, 13, 22]. Thus, these variables should routinely be included in future multivariate analyses. The increased survival of female gender has previously been described [5, 10], but like comparable studies, we could not find any significant effect of gender [13].

FEV₁ < 80% predicted reduced long time survival by multivariate analysis. The predictors of long time survival have been described in different studies. FEV₁ can be treated linearly, with cut off points, or in terms of FEV₁/FVC ratio. One previous study applied FEV1<70% of predicted and found only a small influence on long time survival [13]. The present study found a marked difference between patients with FEV₁ ≥ 80% versus FEV₁<80% of predicted value. The cause of death was not registered in all patients, but the relapse rate in patients with FEV₁ <80% was higher than in the group with FEV₁ ≥ 80%. We did not have sufficient information about smoking to adjust for pack-years. In patients registered for their smoking habits, the consumption of tobacco was similar in the two groups. The explanation for a higher mortality rate in the group with FEV₁<80% is not known and should be further investigated. A hypothesis may be that it is more likely to develop minor pre-cancerous lesions when tobacco smoke has caused lung injury in patients suffering from chronic obstructive lung disease.

Strengths of this study were the long observation time and that all operated patients were included. Thus, the study reflected the complete patient group and the hard end points were easily assessed, except for the missing early postoperative data in two patients. A major limitation is the retrospective design of the study. Although all operated patients were included, there may have been selection bias as the surgeons selected their cases. Referral of some advanced and high risk cases to the regional hospital may also have contributed to a better long time survival in this patient group. The main variables well known to influence on survival were included, but the relatively low number of patients in this study made it impossible to adjust for too many factors in the multivariate analysis.

This study has shown that lung cancer surgery performed in a county hospital with surgeons from teaching hospitals can be performed with good results. The 30 days mortality rate was low and the complication rate was in the range of previous studies. Predictors of reduced long time survival were age over 70 years, advanced preoperative stage and FEV₁<80%. The effect of pulmonary function on long time survival should be investigated in a larger study, the quality of surgery should be registered prospectively.