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ORIGINAL ARTICLE |
Thoracic Surgery Unit, University Hospital of Siena, Siena, Italy
1 Thoracic Surgery Unit, Spedali Civili Riuniti, Brescia, Italy
Cristian Rapicetta, MD, Tel: +39 0577 586 140; Fax: +39 0577 586 140; Email: rapsody2000{at}alice.it, Thoracic Surgery Unit, University Hospital of Sienna, Viale Bracci 1 – 53100, Siena, Italy.
ABSTRACT
To analyze short- and long-term results of surgery in octogenarians, we reviewed data of 96 consecutive patients aged 80 years or more who were operated on for non-small-cell lung carcinoma from 1990 to 2005. Risk factors for complications, perioperative mortality, and long-term survival were assessed by univariate and multivariate analysis. Major complications developed in 17 (17.7%) patients, leading to death in 9 (9.4%) of them. Resection of more than 1 lobe, cardiorespiratory comorbidity, PaO2 < 75 mm Hg, and CO diffusion capacity <60% were predictive of major complications; extended resection was also predictive of 30-day mortality. The overall 5-year survival rate was 38%, with a significant difference between stage I/II and stage III. In multivariate analysis only pathological stage was related to long-term survival. Surgery is feasible for octogenarians, and even patients in stage II can achieve remarkable survival.
Key Words: Octogenarians • Carcinoma • Non-Small-Cell Lung • Pneumonectomy • Postoperative Complications • Survival Rate
INTRODUCTION
As the world population ages, a growing number of octogenarians are presenting with a resectable lung tumor.1 Surgical resection remains the treatment of choice for the early stages of non-small-cell lung carcinoma (NSCLC), but the surgical risk becomes higher with age because of increased prevalence of cardiovascular and pulmonary morbidity and poor performance status.2,3 Although several studies have shown that long-term survival after surgery can be achieved in a significant proportion of octogenarians, the role of surgery is still debated for patients aged 80 years or more, and the majority are managed by a nonsurgical approach.1,4–9 Consequently, most series have a small number octogenarians so it is difficult to define risk factors in these patients. It is possible that more octogenarians could be successfully operated on, but accurate selection of patients is mandatory to avoid an excessively high incidence of complications and mortality. The aim of this study was to analyze the prognostic factors for complications and long-term survival in a cohort of 96 octogenarians operated on for NSCLC.
PATIENTS AND METHODS
The lung cancer database of the Thoracic Surgery Unit at the University of Siena was reviewed to identify all patients aged 
80 years who underwent intended curative lung resection for NSCLC from January 1990 through December 2005. There were 96 such octogenarians, representing 5.6% of 1,711 lung resections performed during that period. The percentage of octogenarians having pulmonary resection for NSCLC in our unit increased steadily from 2.7% in 1990 to 14% in 2005. There were 84 men and 12 women aged 80–89 years (median, 82 years); data are given in Table 1
. Most had a history of cigarette smoking, with 40 median pack-years (range, 2–240 median pack-years). The median value of forced expiratory volume in 1 second (FEV1) was 1.56 L (range, 0.63–2.67 L). Comorbidities were mainly cardiopulmonary (Table 2); coronary artery disease was defined as a history of myocardial infarction, coronary stenting or bypass, or angina pectoris. Ten (10.4%) patients had a previous malignancy, with no evidence of active disease at the time of evaluation for their new primary lung tumor. Almost all patients (97.9%) were in Eastern Cooperative Oncology Group status 0 or 1. Assessment included history, physical examination, routine blood tests, electrocardiogram, echocardiography, blood gas analysis, spirometry, and estimation of CO diffusion capacity of the lung. Cardiac stress tests and coronary angiography were performed when indicated by history of angina pectoris or by significant ischemic signs in the basal electrocardiogram, whereas cardiorespiratory tests and/or lung perfusion scintigraphy were undertaken in cases of poor pulmonary function as 2nd level tests. Clinical staging was based on bronchoscopy, computed tomography (CT) of the chest, abdomen, and brain, as well as bone scintigraphy. Mediastinoscopy was carried out electively in cases of enlarged mediastinal lymph nodes on CT (short axis > 1 cm) with an irregular pattern of perfusion. Positron-emission tomography was used in the last 7 consecutive patients: it was positive at the site of the primary tumor only. Indications for surgery were established on the basis of resectability of the disease and operability of the patient. Every effort was made during preoperative staging to exclude locally extending disease because of the known poor survival prognosis. Operability of the patient was judged by the surgeon together with a pneumologist and anesthesiologist on the basis of preoperative functional status (we did not considered any age limit as a contraindication per se to surgery, although we believe that an age higher than medium life expectancy should be the limit not only for surgery but also for medical treatment of lung cancer). Our surgical policy favored lobectomies over sublobar resections, and whenever possible, we avoided pneumonectomy. Sublobar resection was preferred in cases of poor respiratory function and/or severe cardiovascular comorbidities, and was considered a compromise. No patient received neoadjuvant therapy as we denied surgery to patients with lung cancer in clinical stage III or IV because of the very poor short- and long-term postoperative prognosis. Adjuvant therapy was administered when unforeseen lymph node disease or residual disease was found on pathologic examination of specimens. There were 12 cases defined as stage IIIA by N2 disease in 8 and by T3N1 disease in 4. Adjuvant chemotherapy was administered to 4 patients in stage IIIA and in 2 in stage IIIB, and radiotherapy to 2 in stage IIIA.
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Binary logistic regression analysis was used to discriminate independent risk factors for major complications and 30-days mortality after surgical resection. Long-term survival curves were computed by the Kaplan-Meier method, and compared using the log-rank test. Cox regression analysis was used to determine the significance of prognostic factors for long-term survival, using a stepwise model.
RESULTS
One or more complication developed in 42 patients, giving overall morbidity of 44%. Major and minor complications are listed in Table 3. Multiple complications occurred in 5 patients. Of the 17 major complications, 9 led to death, giving an operative mortality rate of 9.4%. The median postoperative hospitalization was 8 days, although 7 patients had a length of stay > 2 weeks. Ten patients were discharged to a convalescent care facility, 6 received home physical therapy, and the other survivors were discharged home without need of further professional rehabilitation services. No patient suffered permanent or prolonged disability as a result of pulmonary resection.
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and 5. At a mean follow-up of 42 months (range, 8 months to 12 years), 46 (47.9%) patients were alive and 50 (52.1%) had died. The cause of late death was cancer-related in 29/41 (71%) patients. The overall 3- and 5-year actuarial survival rates were 51% and 34%, respectively, with a median survival of 3.7 years (95% confidence interval, 2.7–4.6 years). The 5-year survival rate was significantly better in stage I disease compared to stage III (60% vs. 14%; p < 0.001), and in stage II compared to stage III (42% vs. 14%; p = 0.046), but there was no statistical difference in 5-year survival rates between stage I and stage II (p = 0.39; Figure 1). Using the Cox proportional hazard model of multivariate analysis, only pathological stage of disease was an independent predictor of long-term survival (p = 0.003): stage II or more carried a relative risk of death of 4.2 (Table 6).
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Although recent studies have demonstrated acceptable long-term survival after lung cancer surgery in octogenarians, elderly patients are less likely to undergo surgical resection because advanced age is an important risk factor for postoperative complications and death.1–6,9,12–14 Despite an improvement in early outcome in the past 10 years due to improved selection, anesthesiology, and clinical management, the risk of life-threatening complications in octogenarians remains variable, with operative mortality ranging from 0% to 21%. Harvey and colleagues15 contrasted a 1.6% risk in patients 70–79-years old with a 17.6% risk in octogenarians. Naunheim and colleagues12 reported that even among octogenarians, increasing age was a negative factor. The crucial issue is to select those with the best chance of avoiding complications, who would ultimately have a survival benefit after pulmonary resection.
The 9.4% operative mortality observed in this series is similar to that in other reports covering the same time period, but it was notably higher in patients who required extended resection (> 1 lobe, or chest wall and lung en bloc).11–19 The mortality rates after pneumonectomy and bilobectomy were 22% and 25%, respectively; it is well known that operative mortality is substantial in elderly people having extended resection, especially a right-sided pneumonectomy with mortality exceeding 20%.2,16,17 The British Thoracic Society noted that pneumonectomy is associated with a higher risk of mortality in the elderly, and that age should be a factor in deciding suitability for pneumonectomy.17 We now believe that pneumonectomy should be avoided in an octogenarian, and lesions not resectable by a standard lobectomy should be treated nonsurgically. We also believe that resections involving the chest wall should be avoided as they carry an increased mortality rate, as reported by Romano and Mark3 and Thomas and colleagues.18 The mortality rate was acceptable after lobectomy (8.4%) and 0% after wedge resection or segmentectomy. In addition to the extent of resection, we identified cardiopulmonary comorbidities as predictive of major complications. This supports the hypothesis that the potential association between advanced age and operative mortality is a reflection of increased comorbidity rather than age per se. We observed 17 major complications (mainly cardiopulmonary) in 16 patients, and is noteworthy that they led to death in more than half of them, highlighting the fact that octogenarians have poor cardiorespiratory reserve, and should be carefully selected with attention to comorbidity.
Pulmonary status was assessed by blood gas analysis and spirometry, including measurements of forced vital capacity, FEV1, and maximal voluntary ventilation. Octogenarians with PO2 < 65 mm Hg or PCO2 > 45 mm Hg and/or maximal voluntary ventilation or FEV1 < 50% of predicted are considered for sublobar resection. Because CO diffusion capacity was an independent predictor of postoperative complications, a calculation of estimated postoperative CO diffusion capacity as % of predicted, using either the lung scan for pneumonectomy or an anatomical equation for bilobectomy, might be a useful adjunct to the standard evaluation to improve the selection process.
Cardiac complications developed frequently during the postoperative period. All patients had an echocardiogram, but exercise stress testing was only performed in cases of symptomatic angina, history of infarction, or electrocardiographic abnormalities. The efficacy and cost-effectiveness of exercise stress testing or dipyridamole thallium scanning as screening tests is controversial, but we should probably use a lower threshold for these 2nd- and 3rd-level investigations in octogenarians; when they are positive, it is useful to proceed to coronary angiography because patients found to have significant coronary lesions amenable to angioplasty can be successfully operated on after 2 months (3 cases in our experience). On the other hand, if coronary artery bypass surgery is required, we prefer to manage the patient nonsurgically with radiotherapy because we believe that combined heart-lung surgery carries an excessive risk in advanced age.19
Long-term survival is also of critical importance in this patient population with limited natural life expectancy. Although nonsurgical treatment yields some long-term survivors, the results are consistently worse than surgery, with 5-year survival rates of only 10%–20% after definitive radiotherapy.20 Our overall 5-year survival of 35% is consistent with that reported in similar series over the past decade, with 5-year survival rates of 16%–55%.1,4–7 As expected, pathologic stage was an independent prognostic factor for long-term survival, but in contrast to previous studies in octogenarians, our survival figures also justify surgery for patients with stage II NSCLC, with a 5-year survival rate of 42%.1,4–6 Survival in stage III disease was uniformly very poor in all series, and it was significantly lower than in younger age groups, probably because fewer older patients were able to tolerate extended surgical procedures and adjuvant therapies. Thus stage III disease should represent an absolute contraindication to surgery. Accurate preoperative clinical staging is imperative and in this respect, greater use of positron-emission tomography appears to be necessary, with invasive staging by mediastinoscopy in doubtful cases. Disease-specific survival was similar to overall survival because cancer-related deaths comprised 71% of the total. This means that even octogenarians with a reduced life expectancy died of cancer rather than comorbidities, suggesting that they should be treated by surgery when the disease is amenable by lobectomy. The quality of life and level of independence after surgery should be a major component in the decision-making process in the elderly. We did not identify any prolonged disability, and the fact that nearly 80% of octogenarians in this cohort were discharged home directly suggests that most were able to resume their preoperative lifestyle.
It was concluded that age 80 years is neither a contraindication to operative treatment nor a routine indication for lesser resection. Our experience demonstrates that healthy octogenarians with NSCLC can be offered surgery with an acceptable risk if extended resections are avoided. The presence of comorbidities (cardiorespiratory in particular) and extent of resection predict increased operative risk. On the other hand, complete and accurate clinical staging is crucial because pathological stage is the only predictor of long-term survival.
REFERENCES
Asian Cardiovasc Thorac Ann 2009;
17:147-152
© 2009 by SAGE Publications
DOI: 10.1177/0218492309103295
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