(Chest. 2005;128:1557-1563.)
© 2005
American College of Chest Physicians
Advanced Age Is Not Correlated With Either Short-term or Long-term Postoperative Results in Lung Cancer Patients In Good Clinical Condition*
Shigeki Sawada, MD, PhD;
Eisaku Komori, MD, PhD;
Naoyuki Nogami, MD, PhD;
Akihiro Bessho, MD, PhD;
Yoshihiko Segawa, MD, PhD;
Tetsu Shinkai, MD, PhD;
Masao Nakata, MD, PhD and
Motohiro Yamashita, MD, PhD
* From the Departments of Thoracic Surgery (Drs. Sawada, Komori, and Yamashita) and Medical Oncology (Drs. Nogami, Bessho, Segawa, and Shinkai), National Hospital Organization Shikoku Cancer Center, Ehime; and Division of Thoracic and Cardiovascular Surgery (Dr. Nakata), Kawasaki Medical School, Kawasaki, Japan.
Correspondence to: Shigeki Sawada, MD, PhD, Department of Thoracic Surgery, Shikoku Cancer Center, Horinouchi 13, Matsuyama, Ehime, 790-0007, Japan
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Abstract
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Objectives: Several investigators have reported that operative mortality in the elderly is acceptable. However, their patients are potentially biased with regard to some factors such as performance status (PS) and comorbidity. In this study, we discuss surgical indications for the elderly and effects on perioperative mortality and prognosis.
Study design: A retrospective study was carried out by reviewing the records of 1,114 patients who were referred for treatment of non-small cell lung cancer between January 1993 and December 2002. The patients were classified into younger (
75 years of age) and elderly (
76 years of age) groups. The histologic subtype, TNM stage, Eastern Cooperative Oncology Group PS, and treatment were reviewed for members of each group, and the proportion of patients who underwent surgery was compared between the two groups. The surgical procedures, perioperative mortality, and prognosis of the two groups were also compared.
Results: There was a significant difference in the histologic distribution with no difference in TNM staging between the two groups. Regarding treatment, 51.0% of those in the younger group and 36.1% of those in the elderly group underwent surgery. The proportion of elderly patients who underwent surgery was significantly lower than that of the younger patients, mainly due to worse PS and comorbidity in the elderly patients. The perioperative mortality rates for the younger and elderly groups were 0.9% and 4.1%, respectively, with no significant difference, and the overall survival was similar between the two groups.
Conclusions: When compared to younger patients, fewer elderly patients underwent surgery because of worse PS and comorbidity. However, in elderly patients with good PS and no comorbidity, the rate of perioperative mortality and the prognosis were similar to those in the younger patients. Therefore, advanced age only is not a negative factor for surgery in elderly patients.
Key Words: elderly • limited resection • lobectomy • mortality • non-small cell lung cancer • performance status • prognosis
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Introduction
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Lung cancer is one of the most common forms of neoplasms and the leading cause of cancer-related death in Western countries as well as in Japan.1 The peak incidence age was in the sixties in 1987 but shifted to the seventies in 2001 in Japan.2 In addition, there is a general trend worldwide of an increasing incidence of lung cancer of the elderly.
The treatment of choice in patients with stages I, II, and some subsets of stage IIIA cancer is surgery, but this carries with it certain risks. Generally, the surgical risk becomes higher with age, since elderly patients usually have several types of comorbidities and poor performance status (PS), although the perioperative mortality rate is similar between younger and elderly patients.345 The patients reported in previous studies67 were potentially selected in terms of PS and comorbidity, and surgery was performed only in those in good clinical condition.
Another issue to consider is the life span of the elderly, which is naturally shorter than that of younger patients. Lobectomy is now a standard surgical procedure for patients with lung cancer. However, the perioperative mortality rate associated with this procedure is approximately 1%. Lobectomy including bilobectomy is more invasive than limited resection such as segmentectomy and partial resection. When considering the perioperative risks and benefits of surgery, lobectomy might be less beneficial for the elderly compared to the young. To determine if this is true, we reviewed 1,114 non-small cell lung cancer (NSCLC) patients at a single institute and classified them into two groups by using the age of 75 years as an upper and lower cutoff. Differences were then examined for the selected surgical procedures between the young and elderly patients, with special interest paid to the conditions of the elderly patients when determining the surgical modality. We also evaluated the relationships between surgical procedures such as lobectomy or limited resection and the short-term and long-term results in the elderly group to discuss the optimal surgical procedure for these patients.
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Materials and Methods
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A retrospective study was carried out using the lung cancer database of the Shikoku Cancer Center on 1,114 patients with NSCLC who were treated between January 1993 and December 2002. Information regarding the Eastern Cooperative Oncology Group (ECOG) PS, histologic subtype, TNM stage, and treatment, including chemotherapy, radiotherapy, and surgical procedures, was carefully reviewed. The perioperative mortality rate and long-term results were also reviewed if surgery was carried out. TNM stage was determined according to the International Union Against Cancer classification.8
Our treatment diagram is shown in Figure 1
. Chemotherapy and/or radiotherapy were performed in patients with nonresectable stage IIIA, IIIB, and IV cancer; patients with stage I, II, or resectable IIIA or IIIB were candidates for surgery. Preoperative examinations including spirometry, ECG, and arterial blood gas analysis were carried out, and more detail examinations including diffusion capacity of the lung for carbon monoxide, ultrasound cardiography, and a 6-min walking test were added if necessary. Lobectomy, bilobectomy, or pneumonectomy were indicated if a patient had a predicted FEV1 of 0.8 L, a PS of 0 or 1, and no or slight comorbidity. For a predicted FEV1 of < 0.8 L and/or moderate comorbidity, limited resection was considered. Surgical resection was not indicated for patients with PS 3 or severe comorbidity. Hilar and mediastinal lymphoadenectomy were performed in case more than segmentectomy was required.
Data Analysis
The differences in the proportions of histologic subtypes, TNM stage, PS, pulmonary function status, treatment, surgical procedure, and perioperative mortality rate were compared using the 
2 method between the younger ( 75 years of age) and elderly ( 76 years of age) groups. The surgical procedures were classified into three groups: limited resection, lobectomy, and pneumonectomy. Segmentectomy and partial resection were classified as limited resection. Lobectomy and bilobectomy were classified as lobectomy. Death within 30 days postoperatively was considered to be perioperative death. In this study, prognostic data were analyzed only in patients who underwent limited resection and lobectomy, since the number of pneumonectomies was small. The overall survival and disease-specific survival curves were calculated using the Kaplan-Meier method and compared using the log-rank test. For disease-specific survival analysis, patients who died of any cause other than lung cancer were censored at the time of death. As subset analysis, in the elderly, the overall survival and disease-specific survival rates were compared in terms of the surgical procedures (lobectomy vs limited resection). In addition, the overall and disease-specific survival rates of the elderly treated by lobectomy were also compared to those of the younger patients treated in the same manner. A p value < 0.05 was considered significant. Statistical analysis was performed using statistical software (Version 13; SPSS; Chicago, IL).
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Results
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Demographics and Clinical Presentation
Patient characteristics are shown in Table 1
. The younger and elderly groups consisted of 917 patients (82.3%) and 197 patients (17.7%), respectively, and there was no difference in the male/female ratio between the two groups. Histologic examination revealed that adenocarcinoma was predominant in both groups. However, the incidence of adenocarcinoma in the younger patients (67.6%) was significantly higher than that in the elderly patients (47.7%). In contrast, the incidence of squamous cell carcinoma in the elderly patients (44.2%) was higher than that in the younger patients (23.2%). There was no difference in the distribution of the TNM stages between the two groups (p = 0.225), and the PS of the elderly patients was significantly worse than that of the younger patients (p < 0.001). In addition, the proportion of elderly smokers was significantly higher than that of younger smokers (p = 0.007). Concerning respiratory function, the percentages of patients with vital capacity < 70% and PaO2 < 70 mm Hg in the elderly patients were significantly greater than those in the younger patients (p = 0.005 and p = 0.001, respectively).
Five hundred thirty-four of the 1,114 patients underwent surgery, and the percentage of younger patients who underwent surgery (51.0%) was significantly higher than the percentage of the elderly patients (36.1%) [p < 0.001]. Surgical procedures are shown in Table 2
. Limited resection, including partial resection and segmentectomy, was performed in 86 younger patients (18.4%) and in 18 elderly patients (24.3%), while lobectomy was performed in 369 younger patients (78.8%) and in 55 elderly patients (74.3%). There was no significant difference in the selection of surgical procedures.
Four patients (0.9%) in the younger group and three patients (4.1%) in the elderly group died perioperatively, and there was a trend toward a higher perioperative mortality rate in the elderly group than in the younger group, although there was no significant difference (p = 0.087) [Table 2]. The background and cause of death of these seven patients are shown in Table 3 . Causes of death were pulmonary embolism (n = 2), pneumonia (n = 1), and respiratory failure (n = 4), all associated with lobectomy.
The median follow-up interval was 30 months (range, 0 to 123 months). The overall and disease-specific survival curves are shown in Figure 2
. There was a trend toward an inferior overall survival rate in the elderly group compared to the younger group, but this difference was not statistically significant (p = 0.193). In addition, there was no difference between the younger and elderly groups in disease-specific survival (p = 0.892). Lobectomy and limited resection in the elderly patients were compared with respect of the rates of overall survival and disease-specific death (Fig 3
). In elderly patients, there were no differences in both overall survival and disease-specific survival rates between the different surgical procedures. However, in the overall survival rate, during the early period after surgery, the elderly patients who underwent lobectomy had an associated inferior survival rate compared to those who underwent limited resection (Fig 3, top, A). Lobectomy between the younger and elderly groups was compared using the overall survival and disease-specific survival rates (Fig 4
), and there were no significant differences found. However, in the overall survival rate, during the early period after surgery, the elderly patients had an associated inferior survival rate compared to the younger patients.
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Discussion
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The world population is aging, and the proportion of elderly patients with lung cancer is increasing. In this study, we found that elderly patients had worse PS and greater comorbidity than the younger patients, but the same surgical procedure can be performed and similar outcomes can be expected with respect to perioperative mortality and long-term results as long as patients who are > 75 years old have good PS and no or slight comorbidity.
In this study, we considered patients > 76 years old as elderly, but there is no clear definition for this distinction. In most of the literature, the age of 70 years is considered to be the cutoff.9101112 In our data, 66% of patients would have been classified into the younger group and 34% would have been classified into the elderly group if the age of 70 years was used as the cutoff. We considered that it would have been difficult to clarify the differences between the younger and elderly groups with such a group balance. Therefore, in this study we classified the groups using the age of 75 years as the cutoff in order to emphasize the condition of highly aged patients.
Adenocarcinoma was the dominant histologic type of cancer found in both groups. The incidence of adenocarcinoma in the elderly patients was significantly lower than in the younger patients, but the incidence of squamous cell carcinoma was significantly higher, and this trend was also reported in other studies.131415 In our study, the percentage of smokers in the elderly group was significantly higher than in the younger group, and this might have had some influence on the higher percentage of cases of squamous cell carcinoma in the elderly group.
There was no difference in the TNM staging between the groups, although several previous studies161718192021 showed that elderly patients more often have earlier stages, likely due to the slow progress of lung cancer in the elderly, and the tendency of younger patients to ignore or misinterpret nonspecific changes in their health. In contrast to these results, one study11 conducted in Japan did not find a difference in the stage distribution, according to age. The method of lung cancer screening performed in Japan might affect the rate of early detection in the young and therefore led to no difference between the groups.
Several studies22232425 noted that surgical mortality, morbidity, and long-term results in the elderly are acceptable. However, these were not randomized with respect to the patients, and there might have been bias. It is, therefore, not advisable to make generalizations regarding elderly patients. In our study, 51.0% of the younger patients underwent surgery compared to 33.5% of the elderly patients, although the two groups had the same TNM staging distribution. In addition, when looking at the nonsurgical treatments, the number of patients treated with chemotherapy and/or radiotherapy in the elderly patients was less than in patients < 75 years of age, suggesting that the elderly patients had greater comorbidity and worse PS than the younger patients, and that not only surgery but chemotherapy and radiotherapy were not indicated.
Table 4
lists the patients who were > 76 years old and candidates for surgery indicated by their TNM stage but who eventually did not undergo surgery. Factors considered were a poor PS in 5 patients and poor pulmonary function in 13 patients. The remaining 11 patients had moderate comorbidity and a PS of approximately 1 to 2, and were > 81 years old. Surgery could have been safely performed, but when considering their age, PS, comorbidity, and disease status together, we decided to treat them with radiotherapy instead.
A potential criticism of this study is the histologic distribution that was observed: the incidence of adenocarcinoma in younger patients was greater than that in the elderly patients. This could have had an impact on survival that favored the elderly because adenocarcinoma generally has worse prognosis than squamous cell carcinoma. Survival rates by histologic subtype are shown in Figure 5
. Adenocarcinoma showed a better prognosis than squamous cell carcinoma. Therefore, we considered histologic distribution did not impact survival in favor of the elderly in this study at least.
The Kaplan-Meier curve for the overall survival rate in the elderly was inferior to that in the younger group, although this was not significant (Fig 2, top, A); and it was expected that the overall survival of the elderly was inferior to that of the younger, because of their advanced age. However, the Kaplan-Meier curves for disease-specific death were almost identical (Fig 2, bottom, B), suggesting that more elderly patients died of causes other than lung cancer and that other forms of disease had more influence on their prognosis compared with the younger patients.
The Lung Cancer Study Group26 reported in 1995 that limited pulmonary resection does not result in improved perioperative morbidity, mortality, or late postoperative pulmonary function compared with lobectomy. In our study, there was no significant difference, but the early overall survival rate for lobectomy in the elderly was inferior to that for limited resection (Fig 3, top, A). In addition, 3 of 55 elderly patients (5.5%) but only 4 of 369 younger patients (1.1%) died perioperatively after lobectomy. There was a tendency for perioperative mortality after lobectomy in the elderly patients to be higher than that in the younger patients (p = 0.071) [Table 2]. Although the number of patients was not large and the study was not randomized, lobectomy including bilobectomy might have been too invasive; in some cases, limited resection may therefore have been preferable for those > 76 years old.
In our study, the elderly patients with a good PS and no or slight comorbidities could tolerate surgery and be expected to have a long-term survival rate similar to that of younger patients. However, when considering the drop in survival rate during the early survival period after lobectomy compared to limited resection, it is reasonable to consider limited resection as an alternative surgical management for the elderly.
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Conclusions
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There was a difference in the histologic distribution with regard to NSCLC between younger and elderly patients. The proportion of patients treated surgically was less than that in the younger patients due to severe comorbidity and poor PS, although the TNM staging distribution was similar between the groups. However, in elderly patients with a good PS and no or slight comorbidity, surgery was safely performed and long-term results were similar to those in the younger patients. Finally, we suggest that lobectomy including bilobectomy might be too invasive and that limited resection might be more beneficial for patients of advanced age.
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Footnotes
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Abbreviations: ECOG = Eastern Cooperative Oncology Group; NSCLC = non-small cell lung cancer; PS = performance status
Received for publication January 18, 2005.
Accepted for publication March 23, 2005.
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Abstract
Introduction
