Survival and Prognosis After Pneumonectomy for Lung Cancer in the Elderly

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1 and Prognosis After Pneumonectomy for Lung Cancer in the Elderly Yutaka Mizushima, MD, Hirofumi Noto, MD, Shigeki Sugiyama, MD, Yoshinori Kusajima, MD, Ryouhei Yamashita, MD, Tatsuhiko Kashii, MD, and Masashi Kobayashi, MD First Department of Internal Medicine and First Department of Surgery, Toyama Medical and Pharmaceutical University, Toyama, Japan Background. The number of elderly patients with lung cancer is increasing. This study was undertaken to assess the validity of pneumonectomy for the treatment of lung cancer in this patient group. Methods. Twenty-seven patients 70 years old or older (elderly group) and 95 patients younger than 70 years (younger group) who underwent pneumonectomy between January 1985 and March 1996 formed the study group. In the elderly group, 22 patients had squamous cell carcinoma, 2 had adenocarcinoma and 3, small cell carcinoma; 1 patient was in postoperative stage I, 4 patients were in stage II, 14 in stage IIIA, 5 in stage IIIB, and 3 in stage IV of the disease. The only significant differences in patient characteristics between the two groups were the percentage of patients undergoing right pneumonectomy and the percentage of patients receiving chemotherapy or radiotherapy within 3 months before or after operation or both times. Results. The prognosis for the elderly group was comparable to that of the younger group for all stages of the disease; the overall 5-year survival rate was 30.5% for the younger group and 11.5% for the elderly group. However, operation-associated mortality was significantly higher in the elderly group (22.2% versus 3.2%; p < 0.005). The prognosis was better for patients with a centrally located tumor than a peripheral tumor in both groups [13.5% versus 2.0% in the elderly group and 46.7% versus 5.2% (p < 0.01) in the younger group] and significantly better for patients having a left pneumonectomy than a right pneumonectomy in the younger group (46.7% versus 5.2%; p < 0.01) but not in the elderly group (13.7% versus 22.2%). Adjuvant treatment did not have any beneficial effect on the prognosis in either group. Conclusions. Pneumonectomy for lung cancer in elderly patients appears to be justified because the outcome in our study was comparable with that for the younger patients. However, it should be performed only in carefully selected patients because of the increased operative risk. (Ann Thorac Surg 1997;64:193 8) 1997 by The Society of Thoracic Surgeons Accepted for publication Dec 27, Address reprint requests to Dr Mizushima, First Department of Internal Medicine, Toyama Medical and Pharmaceutical University, Toyama, , Japan. The incidence of lung cancer is high for men and increases with age. The number of elderly people has been growing in Japan, and since 1993, lung cancer has become the leading cause of death in men. Oncologists see an increasing number of elderly patients with lung cancer, and treatment of such patients is becoming very important in many countries [1 5]. Pulmonary resection is still the most effective treatment of lung cancer and is associated with long-term survival. Lobectomy is now the most frequently performed surgical procedure for lung cancer. Most surgeons prefer not to do a pneumonectomy, especially on elderly patients, because of the resulting impairment of pulmonary function, but this operation is often necessary for lung cancer. There are several reports [2, 6 10] on the surgical treatment of lung cancer in the elderly, but we could find none published in the past decade specifically dealing only with patients having pneumonectomy. In this study, the clinical features of patients 70 years old or older who underwent pneumonectomy were analyzed, and the validity of pneumonectomy for the treatment of lung cancer in the elderly was assessed. Material and Methods The study consisted of 122 patients (111 men, 11 women) who underwent pneumonectomy for lung cancer between January 1985 and March Pneumonectomy was performed only for lesions that could not be removed with a lesser resection. Patients 70 years old or more at the time of operation were designated as the elderly group (age range, 70 to 79 years, mean age, 73.6 years) and patients younger than 70 years as the younger group (age range, 36 to 69 years; mean age, 59.7 years). Histologic typing was done according to the World Health Organization histologic classification, and disease was staged postsurgically by the TNM criteria for cancer staging of the Union Internationale Contre Cancer [11]. Operation-associated mortality included deaths within 30 days after operation and in-hospital deaths. Data are shown as the mean the standard error. A 1997 by The Society of Thoracic Surgeons /97/$17.00 Published by Elsevier Science Inc PII S (97)

2 194 MIZUSHIMA ET AL Ann Thorac Surg PNEUMONECTOMY FOR LUNG CANCER IN ELDERLY 1997;64:193 8 Table 1. Summary of Patient Data a,b Variable (n 95) (n 27) Sex Male/female 86/9 (91/9) 25/2 (93/7) Postoperative stage I 7 (7) 1 (4) II 11 (12) 4 (15) IIIA 42 (44) 14 (52) IIIB 30 (32) 5 (19) IV 5 (5) 3 (11) Histologic type Squamous cell 63 (66) 22 (82) Adenocarcinoma 23 (24) 2 (7) Small cell 5 (5) 3 (11) Large cell 3 (3) 0 Adenosquamous 1 (1) 0 Location Right/left 41/54 (43/57) 6/21 (22/78) c Central/peripheral 53/42 (56/44) 18/9 (67/33) Pulmonary function tests (n 90) (n 24) FVC (L) d FEV 1 (L) d Normal 48 (53) 9 (38) Obstructive 26 (29) 8 (33) Restrictive 8 (9) 6 (25) Combined 8 (9) 1 (4) Arterial tension (mm Hg) (n 84) (n 24) PaO PaCO Adjuvant treatment e Radiotherapy 23 (24) 3 (11) Chemotherapy 26 (27) 4 (15) Both 16 (17) 1 (4) None 30 (32) 19 (70) f a Numbers in parentheses are percentages. b Where applicable, data are shown as the mean the standard error. c Significance: p 0.05 versus younger group. d Significance: p 0.01 versus younger group. e This refers to treatment within 3 months before or after operation or both. f Significance: p versus younger group. FEV 1 forced expiratory volume in 1 second; FVC forced vital capacity; PaCO 2 arterial carbon dioxide tension; PaO 2 arterial oxygen tension. survival curve was constructed by the Kaplan-Meier method and statistically evaluated by the Cox-Mantel test. Time zero was the date of operation, and June 30, 1996, was the closing date for the analysis. One patient was lost to follow-up; therefore, all patients except 1 were included in the analysis. Other factors were evaluated by the 2 test or Student s t test, and a p value of less than 0.05 was considered significant. Results Comparison of Clinical Features Among the 122 patients who underwent pneumonectomy for lung cancer during the study period, 27 (22%) were in the elderly group and 95 (78%) in the younger group. The characteristics of the two groups are shown in Table 1. Forced vital capacity and forced expiratory volume in 1 second were significantly lower in the elderly group, but arterial oxygen tension was similar in the two groups. The percentage of patients undergoing a right pneumonectomy was significantly lower in the elderly group (22% versus 43%; p 0.05). The percentage of patients receiving adjuvant treatment within 3 months before or after operation or both times was significantly lower in the elderly group (30% versus 68%; p 0.005). There were no other significant differences between the two groups. Comparison of Prognosis The prognosis for patients according to disease-related factors was compared between the two groups (Table 2). There were no significant differences in prognosis by any stage of the disease (Fig 1), location (right or left, central or peripheral), and adjuvant treatment. Concerning histologic type, a comparison was made only for squamous cell carcinoma, and no difference was observed. The prognosis for patients in both groups was affected not only by the stage of the disease but also by the location of the tumor (central versus peripheral). The prognosis was better for patients with a central type than a peripheral type with a 5-year survival rate of 46.7% versus 5.2% (p 0.01) in the younger group and 23.8% versus 0% in the elderly group (Fig 2). The prognosis for patients undergoing left pneumonectomy compared with right pneumonectomy was significantly better in the younger group (40.9% versus 17.1%; p 0.01) but not in the elderly group (13.7% versus 22.2%). Table 2. Comparison of Prognosis According to Disease- Related Factors Between Groups a,b Factor 5-Year (%) Median Time (mo) 5-Year (%) Median Time (mo) Stage I II (18) (5) IIIA (41) (14) IIIB (30) (5) I IV (94) (27) Histologic type Squamous cell (62) (22) Location Right (41) c (6) Left (53) (21) Central (52) (18) Peripheral (42) d (9) Adjuvant treatment e Yes (65) (8) No (29) (19) a Numbers in parentheses are numbers of patients. b There were no significant differences between the two groups. c Significance: p 0.01 versus left pneumonectomy. d Significance: p 0.01 versus central. e This refers to treatment within 3 months before or after operation or both.

3 Ann Thorac Surg MIZUSHIMA ET AL 1997;64:193 8 PNEUMONECTOMY FOR LUNG CANCER IN ELDERLY 195 To identify reasons for the poorer prognosis in patients with a peripheral tumor and in patients undergoing a right pneumonectomy, we compared clinical features between patients with a central versus a peripheral location of the tumor and between patients having a right versus a left pneumonectomy. The percentages of patients with adenocarcinoma (49% versus 0%; p 0.005) and patients with N2 or N3 disease (71% versus 35%; p 0.005) were significantly Fig 2. curves for groups with central location and peripheral location of tumor: (A) younger group and (B) elderly group. higher in patients with a peripheral tumor than a central tumor (Table 3). The percentage of patients in stages I or II was significantly lower among those having a right Table 3. Comparison of Clinical Features Between Central and Peripheral Location Groups Feature Central (n 71) Peripheral (n 51) Histologic type Squamous cell 66 (93) 19 (37) Adenocarcinoma 0 25 (49) a Other 5 (7) 7 (14) Stage I II 18 (25) 5 (10) b IIIA 31 (44) 25 (49) IIIB IV 22 (31) 21 (41) T1 T2 22 (31) 12 (24) T3 31 (44) 24 (47) T4 18 (25) 15 (29) N0 19 (27) 8 (16) N1 27 (38) 7 (14) N2 N3 25 (35) 36 (71) a M1 4 (6) 5 (10) Fig 1. curves for younger and elderly groups: (A) all stages (I through IV); (B) stages I and II; and (C) stages IIIA and IIIB. a Significance: p versus central. central. b Significance: p 0.05 versus

4 196 MIZUSHIMA ET AL Ann Thorac Surg PNEUMONECTOMY FOR LUNG CANCER IN ELDERLY 1997;64:193 8 Table 4. Effect of Pneumonectomy on Pulmonary Function in Younger and s a c Variable Preop Postop Preop Postop PaO 2 (mm Hg) R (17) (5) L (29) (7) FVC (L) R (17) (2) L (21) (7) FEV 1 (L) R (17) (2) L (21) (7) a Numbers in parentheses are numbers of patients tested; only patients in whom tests were performed both preoperatively and postoperatively are included. b Where applicable, data are shown as the mean the standard error. c There were no significant differences between the two groups. FEV 1 forced expiratory volume in 1 second; FVC forced vital capacity; L left; PaO 2 arterial oxygen tension; R right. pneumonectomy in the younger group (10% versus 26%; p 0.05). Effect of Pneumonectomy on Pulmonary Function and Surgical Risk The effect of pneumonectomy on pulmonary function was compared between the younger and elderly groups (Table 4). There was no reduction in arterial oxygen tension at rest after pneumonectomy in either group. There were also no significant differences in forced vital capacity and forced expiratory volume in 1 second after pneumonectomy between the two groups. Complications associated with the operation such as pneumonia and bronchial fistula were significantly higher in the elderly group than in the younger group (33.3% versus 8.4%; p 0.005). Operation-associated mortality was also significantly higher in the elderly group (22.2% versus 3.2%; p 0.005) (Table 5). Of the 9 patients who died, 7 had a peripheral location of the tumor. Comment The prognosis for the elderly group was comparable with that for the younger group in all stages of the disease. Also, no significant difference in the prognosis was observed between patients less than 50 years old and patients 50 to 69 years old (data not shown). Therefore, we conclude that age is not a prognostic factor for patients undergoing pneumonectomy. Other researchers [2, 12] have also found that age is not a prognostic factor for patients undergoing surgical resection. In their retrospective study of 80 patients older than 70 years, Harviel and associates [7] reported that the mean Table 5. Operation-Associated Deaths Patient No. Age (y) Sex Stage Location Histology FVC/FEV 1 (L) Pulmonary Function PaO 2 /PaCO 2 (mm Hg) Cause of Death (d) 1 49 M IIIB L, P Sq 4.08/ /38 Bronchial fistula M IIIA R, P Sq 3.55/ /39 Pneumonia acute MI M IIIB R, P Sq 3.43/ /33 ARDS 47 Total 3/95 (3.2%) 4 70 M IIIB L, C Sq 3.47/ /38 Pneumonia M IIIB L, P Sm 3.33/ /39 Acute heart failure M IIIA L, P Ad NT NT Acute respiratory 2 failure 7 72 F II R, C Sq 1.90/ /43 Bronchial fistula M IV R, P Sq NT 78/40 Bronchial fistula M IIIA L, P Sq 1.71/ /34 Pneumonia 60 Total 6/27 (22.2%) a a Significance: p versus younger group. Ad adenocarcinoma; ARDS adult respiratory distress syndrome; C central; FEV 1 forced expiratory volume in 1 second; FVC forced vital capacity; L left; MI myocardial infarction; NT not tested; P peripheral; PaCO 2 arterial carbon dioxide tension; PaO 2 arterial oxygen tension; R right; Sm small cell carcinoma; Sq squamous cell carcinoma.

5 Ann Thorac Surg MIZUSHIMA ET AL 1997;64:193 8 PNEUMONECTOMY FOR LUNG CANCER IN ELDERLY 197 survival was 3.5 months for the untreated group (n 13), 9.8 months for the chemotherapy or radiotherapy group (n 35), and 30.6 months for the resection group (n 22) with an operative mortality rate of 18.2% (4/22). Berggren and co-workers [13] obtained similar results; the 5-year survival rate was 34% for the group having resection with a hospital mortality rate of 15.9% versus 0% for the group without resection. Both groups of authors stated that surgical resection is worthwhile for the treatment of lung cancer in the elderly, despite an increased operative risk. We support this assertion because favorable long-term survival was observed in our study. However, the 5-year survival rate was not high for patients with an advanced stage of the disease: 69% for stage II, 38% for stage IIIA, and only less than 4% for stage IIIB. Therefore, detection of lung cancer at an early stage will be necessary to produce a better outcome. In our study, the 30-day operative mortality rate after pneumonectomy was 4.1% (5/122) for all patients, which is comparable to the 6.2% (44/569) reported by Ginsberg and associates [14], the 6.9% (20/287) of Deneffe and colleagues [15], and the 6.8% (13/191) of Kadri and Dussek [16]. In our study, the mortality rate increased with the age of the patients (5/27 or 11.1% for the elderly group), which is comparable to the mortality rate in a similar group reported by Suemasu and co-workers [9] (4/25 or 16.0%). The finding that operative mortality increases with age has been well reported [14, 15]. However, others [2, 8, 13, 16] have found that the risk of a major complication or operative death is not related to age. Harvey and coauthors [10] reported that significantly increased operative mortality did not occur until age 80 years in 370 patients with non small cell lung cancer treated surgically: the rates were 1.4% (4/289) for patients younger than 70 years, 1.6% (1/64) for patients 70 to 79 years old, and 17.6% (3/17) for patients 80 years old or older. The authors suggested that heparin sodium prophylaxis might be especially important in this last patient group. We agree that more attention should be given to careful preoperative staging, selection of surgical procedure, and routine preoperative and postoperative physical therapy to reduce operative mortality. In a study by Nagasaki and associates [17], the 4 patients who died after pneumonectomy (4/72 or 5.6%) all had a right pneumonectomy (4/30 or 13.3%). In our study, this tendency was not observed; 4 of the patients who died had a right pneumonectomy and 5, a left pneumonectomy. However, 7 of the 9 patients who died had a peripheral location of tumor. Two clinical features were noted to be different between the younger and elderly groups. The first feature is that the percentage of patients undergoing a right pneumonectomy was significantly lower in the elderly group (22% versus 43%; p 0.05). As the reduction in pulmonary function is greater after a right pneumonectomy than a left pneumonectomy (see Table 4), most surgeons tend to avoid performing right pneumonectomy. The second feature is that the percentage of patients receiving adjuvant treatment within 3 months before or after operation or both times was significantly lower in the elderly group (30% versus 68%; p 0.005). This may be due to the fact that doctors and elderly patients tended to avoid chemotherapy or radiotherapy because of the adverse effects. In our study, adjuvant treatment did not have any beneficial effect on the prognosis. The median survival times were almost the same for the patients receiving adjuvant treatment and the patients who did not in both age groups. On this point, the Lung Cancer Study Group [18] in the United States has reported that postoperative mediastinal irradiation was not beneficial for patients with completely resected stage II and stage III epidermoid lung cancer in their randomized trial. There is a clear need of adjuvant treatment for resectable lung cancer, and thus a new strategy will be required. Recently, video-assisted thoracic surgery [19] has become popular for the treatment of lung cancer in Japan. This less invasive procedure may be more beneficial than pneumonectomy in select elderly patients. However, pneumonectomy often is necessary. We have shown in this study that pneumonectomy is justified for the treatment of lung cancer in elderly patients, but it should be done only in carefully selected patients because of the increased operative risk. References 1. Kusumoto S, Koga K, Tsukino H, Nagamachi S, Nishikawa K, Watanabe K. Comparison of survival of patients with lung cancer between elderly ( 70) and younger (70 ) age groups. Jpn J Clin Oncol 1986;16: Ishida T, Yokoyama H, Kaneko S, Sugio K, Sugimachi K. Long-term results of operation for non small cell lung cancer in the elderly. Ann Thorac Surg 1990;50: Mizushima Y, Kashii T, Yoshida Y, Sugiyama S, Kobayashi M. Characteristics of lung cancer in the elderly. Anticancer Res 1996;16: O Rourke MA, Crawford J. Lung cancer in the elderly. Clin Geriatr Med 1987;3: Zogonel V, Tirelli U, Serraino D, et al. The aged patients with lung cancer. Management recommendations. Drugs Aging 1994;4: Kirsh MM, Rotman H, Bove E, et al. Major pulmonary resection for bronchogenic carcinoma in the elderly. Ann Thorac Surg 1976;22: Harviel JD, McNamara JJ, Straehley CJ. Surgical treatment of lung cancer in patients over the age of 70 years. J Thorac Cardiovasc Surg 1978;75: Breyer RH, Zippe C, Pharr WF, Jensik RJ, Kittle CF, Faber LP. Thoracotomy in patients over age seventy years. J Thorac Cardiovasc Surg 1981;81: Suemasu K, Yoneyama T, Naruke T, Miyazawa N, Tsuchiya R. Surgical treatment of lung cancer in patients over the age of 70 years. Jpn J Clin Oncol 1982;12: Harvey JC, Erdman C, Pisch J, Beattie EJ. Surgical treatment of non small cell lung cancer in patients older than seventy years. J Surg Oncol 1995;60: Mountain CF. A new international staging system for lung cancer. Chest 1986;89 (Suppl):225S 33S. 12. Mane JM, Estape J, Sanchez-Lloret J, et al. Age and clinical characteristics of 1433 patients with lung cancer. Age Ageing 1994;23: Berggren H, Ekroth R, Malmberg R, Naucler J, William- Olsson G. Hospital mortality and long-term survival in relation to preoperative function in elderly patients with bronchogenic carcinoma. Ann Thorac Surg 1984;38: Ginsberg RJ, Hill LD, Eagan RT, et al. Modern thirty-day

6 198 MIZUSHIMA ET AL Ann Thorac Surg PNEUMONECTOMY FOR LUNG CANCER IN ELDERLY 1997;64:193 8 operative mortality for surgical resections in lung cancer. J Thorac Cardiovasc Surg 1983;86: Deneffe G, Lacquet LM, Verbeken E, Vermaut G. Surgical treatment of bronchogenic carcinoma: a retrospective study of 720 thoracotomies. Ann Thorac Surg 1988;45: Kadri MA, Dussek JE. and prognosis following resection of primary non small cell bronchogenic carcinoma. Eur J Cardiothorac Surg 1991;5: Nagasaki F, Flehinger BJ, Martini N. Complications of surgery in the treatment of carcinoma of the lung. Chest 1982; 82: The Lung Cancer Study Group. Effects of postoperative mediastinal radiation on completely resected stage II and stage III epidermoid cancer of the lung. N Engl J Med 1986; 315: McKneally MF, Lewis RJ, Anderson RP, et al. Statement of the AATS/STS Joint Committee on Thoracoscopy and Video Assisted Thoracic Surgery. Ann Thorac Surg 1992;54:1. REVIEW OF RECENT BOOKS Color Atlas of Congenital Heart Surgery Edited by S. Bert Litwin St. Louis, Mosby, pp, illustrated, $ ISBN: Reviewed by David R. Clarke, MD Color Atlas of Congenital Heart Surgery by Dr S. Bert Litwin is a photographic masterpiece containing 634 plates, the vast majority of which are color intraoperative anatomy and technique illustrations accumulated over a 25-year period. The 255-page atlas contains vivid descriptions of often multiple surgical options to deal with a variety of cardiac lesions or situations. In 21 chapters comprising one to six sections each, Dr Litwin covers a spectrum of palliative and corrective surgical alternatives for the treatment of all major categories of congenital heart disease. In most sections of the atlas, surgeons could quibble about the exact approach, choice of patch material, suture technique, or other details. However, none could argue that referring to this work did not in some way increase their level of understanding of a lesion and its repair. Doctor Litwin does not dwell on myocardial preservation or bypass techniques that are rapidly changing in the specialty. With the exception of a few procedures such as the Waterston shunt that are of historical interest, Dr Litwin concentrates on illustrating currently accepted and time-tested techniques for treating commonly encountered congenital cardiac anomalies. The Color Atlas of Congenital Heart Surgery is not intended for the reader with a casual interest in congenital cardiac surgery. The color plates, although clear and accompanied by orientation indicators, are more difficult to comprehend than artists sketches and require intimate knowledge of cardiac anatomy to be useful. However, from this book, residents, fellows, or staff surgeons who are involved in the surgical care of patients with congenital heart disease can obtain a clear picture of the internal anatomy before going into the operating room. In addition, the book enables the pediatric cardiologist and pediatric pathologist to observe the heart from the surgeon s point of view without donning a scrub suit. The positive features of this atlas are too numerous to itemize. No other source includes color illustrations of five different techniques for dealing with coarctation of the aorta. No other source contains 83 plates that show surgical options for handling d-transposition of the great arteries. No other source demonstrates palliative and corrective approaches to tetralogy of Fallot in 73 color photographs. This book does not belong in a bookcase but on the desktop of every physician who participates in the surgical treatment of patients with congenital cardiac defects. Denver, Colorado 1997 by The Society of Thoracic Surgeons Ann Thorac Surg 1997;64: /97/$17.00 Published by Elsevier Science Inc PII S (97)

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