Surgical Resection for Lung Cancer in the Octogenarian

Surgical Resection for Lung Cancer in the Octogenarian* Jeffrey L. Port, MD; Michael Kent, MD; Robert J. Korst, MD, FCCP; Paul C. Lee, MD; Matthew A. Levin, BS; Douglas Flieder, MD; and Nasser K. Altorki, MD, FCCP

Background: As the US population ages, clinicians are increasingly confronted with octogenarians with resectable non-small cell lung cancer. Earlier reports documented substantial risk for surgical resection in this age group. Methods: We reviewed our surgical experience in octogenarians who underwent curative resection from 1990 to 2003. Results: Sixty-one patients underwent resection: 46 lobectomies, 6 segmentectomies, 5 wedge resections, and 4 pneumonectomies. There was one perioperative death (1.6%). The overall complication rate was 38% with a major complication rate of 13%. The average postoperative length of stay was 7 days. Overall 5-year survival was 38%, and 82% for stage IA patients. Patients with more advanced disease had a significantly worse survival. Conclusions: Appropriately selected octogenarians with early stage disease should be offered anatomic surgical resection for cure. These patients can anticipate a long-term survival, and should not be denied an operation on the basis of age alone. (CHEST 2004; 126:733–738) Key words: lung cancer; octogenarians; surgery

US population ages, an increasing number A softheoctogenarians will present with bronchogenic carcinoma. The 2000 US census reported that the population ⱖ 80 years old increased ⬎ 33% during the 1990s, and now represents 4.6% of the total US population.1 Furthermore, of 157,000 US lung cancer deaths in 2003, 31,000 patients (20%) were octogenarians.2 This makes lung cancer the secondleading cause of cancer death among this age group. Clearly, physicians will be increasingly confronted by octogenarians with lung cancer. Surgical resection remains the treatment of choice for early stage lung cancer, yet previous studies3–7 have presented variable results for resection in the elderly. Based on these data and the fact that octogenarians will often present with numerous comorbidities, clinicians have commonly offered less aggressive treatment to this subgroup of patients, with some recommending a nonoperative approach *From the Department of Cardiothoracic Surgery, Weill Medical College of Cornell University, New York, NY. Manuscript received November 25, 2003; revision accepted April 12, 2004. Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (e-mail: [email protected]). Correspondence to: Nasser K. Altorki, MD, FCCP, Department of Cardiothoracic Surgery, Suite M404, Weill Medical College of Cornell University, 525 E 68th St, New York, NY 10021; e-mail: [email protected] www.chestjournal.org

or a less than an anatomic resection.8 However, advances in preoperative and postoperative care and in surgical technique have encouraged many to offer surgical resection to the elderly population. The present report analyzes our experience with lung cancer in octogenarians who underwent an intended, complete, anatomic resection. We reviewed various clinical characteristics and the long-term survival rate.

Patients and Methods Institutional review board approval was obtained for this study. The office records of all patients aged ⱖ 80 years who underwent curative resection for non-small cell lung cancer from 1990 through January 2003 were reviewed. The preoperative assessment of this group included a history, physical examination, routine blood work, ECG, and pulmonary function tests in all patients. A comprehensive cardiac evaluation was performed in those patients considered at risk based on history, clinical examination, or ECG findings. Clinical staging included a CT scan of the chest and abdomen in all patients. Patients suspected of having stage II or III disease also underwent imaging studies to exclude disseminated disease. Mediastinoscopy was routinely performed. Complete resection was planned through either a thoracotomy or thoracoscopy. Mediastinal node dissection was routinely performed for accurate staging. Demographic data collected included age, gender, associated comorbidities, cardiac and pulmonary functional assessment, use of induction therapy, and clinical stage. Perioperative data included the extent of resection, 30-day operative mortality (deCHEST / 126 / 3 / SEPTEMBER, 2004

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fined as death at any time during the initial hospitalization or within 30 days following the operation), complications, length of stay, histology, pathologic stage, and the use of adjuvant therapy. Follow-up was obtained through routine office visits or via telephone contact. All patients were followed up through January 2003. Statistical analysis was performed using SPSS statistical software (SPSS; Chicago, IL). Survival was calculated using the Kaplan-Meier method, and dichotomous variables were compared using the ␹2 test. Results were considered significant at p ⱕ 0.05.

Results Preoperative Assessment Surgical resection was performed in 61 octogenarians, which represented 7% of the 874 curative resections for lung cancer performed during the study period. Within this period, an additional 18 octogenarians were evaluated by the thoracic surgical service and not offered resection. Five of these patients had bulky N2 disease, while the remaining 13 patients were clinically staged as IIIB or IV. As shown in Figure 1, the number of octogenarians who underwent surgical resection at our institution steadily increased throughout the study period. There were 25 men and 36 women, ranging in age from 80 to 87 years (median age, 82 years). Thirtynine patients had a documented smoking history (median, 55 pack-years; range, 20 to 200 pack-years). More than half of the study group (n ⫽ 35, 57%) exhibited comorbidities, most commonly hypertension and coronary artery disease (Table 1). Twenty patients had a history of coronary artery disease,

Table 1—Major Comorbidities Comorbidities

No. of Patients

Hypertension Coronary artery disease COPD Diabetes mellitus Long-term steroid use Cerebrovascular aneurysm

20 20 13 3 3 2

defined as a history of prior myocardial infarction, prior coronary stenting or bypass, or a positive stress test result. Three patients were receiving long-term steroids for their underlying emphysema, and 13 patients (21%) were classified as having moderateto-severe obstructive or restrictive pulmonary disease as defined by the American Thoracic Society guidelines.9 In addition, six patients had previous malignancies with no evidence of active disease at the time of evaluation for their new lung primary. Pulmonary function as measured by FEV1 ranged from 0.84 to 2.85 L, averaging 1.7 L (85% predicted). Clinical TNM stage is shown in Table 2. Two patients were treated with induction chemotherapy, and one patient received preoperative chemoradiation. Surgical Procedure Forty-six lobectomies, 4 pneumonectomies, 6 segmentectomies, and 5 wedge resections were performed. The six segmental resections were done in patients with peripherally located lesions. Four patients underwent an intentional segmentectomy; in two patients, a segmentectomy was done due to poor pulmonary functions. Five patients underwent a simple wedge resection either due to a previous major lung resection (n ⫽ 1) or severe impairment of pulmonary function in the judgment of their treating physician. Three patients underwent an associated chest wall resection, and one patient had a concurrent coronary artery bypass graft. An R0 resection (no residual microscopic disease) was performed in 58 patients (95%), and an R1 resection (residual

Table 2—Clinical and Pathologic Staging No. of Patients TNM Stage

Figure 1. Trend in the number of octogenarians who underwent resection at The New York Hospital, Weill-Cornell Medical Center. 734

IA IB IIA IIB IIIA IIIB

Clinical

Pathologic

32 19 0 5 5 0

21 23 3 8 5 1*

*Upstaged from clinical stage IIB. Clinical Investigations

Table 3—Postoperative Complications Complications

No. of Patients

Major Reintubation Pneumonia Myocardial infarction Take back for bleeding Empyema Gastric perforation Minor Arrhythmia Prolonged air leak Urinary tract infection Delirium

4 2 2 1 1 1 13 1 4 1

microscopic disease) was performed 3 patients (5%). The median postoperative length of stay was 7 days, although four patients had a length of stay ⬎ 2 weeks. Complications One patient, an 82-year-old man with a history of coronary artery disease, died 3 days postoperatively of cardiac arrest. Hospital and 30-day operative mortality were 1.6%. Complications occurred in 23 patients, for a total morbidity of 38%. Eleven major complications occurred in eight patients (13%). Major and minor complications are listed in Table 3. Univariate analysis revealed no correlation between existing comorbidities or impaired pulmonary function and postoperative complications (Table 4). Histology and Stage of Disease Pathologic evaluation revealed 38 adenocarcinomas, 15 squamous cell carcinomas, 5 bronchoalveolar carcinomas, and 3 large cell carcinomas. Mean tumor size was 3.4 cm. Pathologic stage is shown in Table 2. One patient was clinically staged as IIB and was upstaged to IIIB following resection.

Figure 2. Overall 5-year survival.

for all patients was 32 months (median, 18 months). As shown in Figure 2, overall 5-year survival for patients with stage IA disease was 82%, vs 18% for patients with stage II/III disease (p ⫽ 0.022 by log-rank test). Overall survival for stage IB was 33%. Disease-specific survival is shown in Figure 3 and was similar to overall survival. Discussion The US population is aging, and the incidence of octogenarians with lung cancer is increasing concomitantly. While surgical resection remains the standard of care for treatment of early stage lung cancer, there are those who have suggested that a less aggressive approach be applied to octogenarians. Previous studies10,11 have reported substantial perioperative mor-

Survival Overall 5-year survival for the entire cohort was 38%, with a median survival of 3.7 years (95% confidence interval, 2.7 to 4.6 years). Mean follow-up

Table 4 —Representative p Values for Univariate Analysis Variables Single comorbidity (any) Multiple comorbidities (two or more) Obstructive/restrictive airway disease

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p Value 0.184 0.252 0.591

Figure 3. Disease-specific 5-year survival. CHEST / 126 / 3 / SEPTEMBER, 2004

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bidity and mortality among octogenarians, and proposed that either nonsurgical treatment or a less than anatomic resection is more appropriate for this age group. Predictably, the treatment of the elderly with lung cancer differs considerably from their younger counterparts. In a review of Medicare-insured patients in Virginia, patients ⱖ 65 years old with localized lung cancer were only one third as likely to undergo resection compared with younger patients.12 Indeed, for each decade of life after 65 years of age, the likelihood of undergoing resection declined by 65%. The only variable that predicted the probability of receiving surgical therapy vs radiation therapy, or in fact any therapy vs observation alone, was age. The extent of a comorbidity was not a predictor of therapy. These findings suggest that resection is often not recommended to the elderly, even though they may be technically resectable and have no medical contraindications to surgery. Several biases are likely to contribute to these differences in practice. The first is the impression that octogenarians have a limited life expectancy, and are as likely to die from other conditions as they are to die from lung cancer. The second is a belief that the rate of complications and death following surgery is prohibitively high in the elderly. Finally, radiation therapy or observation alone may be thought to yield results that are not significantly inferior to surgery in the elderly. The impression that the life expectancy of an octogenarian with lung cancer is limited by death from natural causes is not supported by US census data. In fact, the average life expectancy for an 80 year old living in the United States is now an impressive 8.6 years (7.6 years for men, and 9.1 years for women).1,13 This translates into an overall 5-year survival for an age- and gender-matched population

Figure 4. Five-year survival of an age- and gender-matched population.

of 80%, as calculated from the life tables (Fig 4). Furthermore, the majority of this time is anticipated to be years of active and independent life.14,15 Given these facts, it seems likely that the greatest impact on an octogenarian’s survival and quality of life will be their cancer-related mortality rather than their age. Reluctance to recommend surgery for the elderly is partly based on the expectation that the rate of complications and mortality is higher in this group of patients. Older reports, such as that of the Lung Cancer Study group,3 showed a mortality rate of 8.1% for octogenarians undergoing anatomic pulmonary resection, compared with 1.6% in patients ⬍ 65 years old. However, other studies, as well as the present report, suggest significant improvement in the results of surgery for lung cancer in the elderly (Table 5). For example, in 1998 the Japanese Association of Chest Surgery reported a modern-day benchmark for mortality following lung resection. In

Table 5—Reported Experience With Surgical Resection for Lung Cancer in Octogenarians*

Source

Years Covered

No. of Patients

Morbidity, %

Operative Mortality†, %

Ginsberg et al3 1983 Shirakusa et al5 1989 Osaki et al6 1994 Naunheim et al16 1994 Pagni et al10 1997 Wada et al4 1998 Hanagiri et al15 1999 Aoki et al17 2000 Port et al, 2003 (present report)

1979–1983 1978–1987 1974–1991 1981–1991 1980–1995 1994 1992–1995 1981–1998 1990–2003

37 31 33 37 54 225 18 35 61

NS 51 67 45 45 NS 50 60 38

8.1 13 21 16 3.7 2.2 0 0 1.6

5-yr Survival Overall, %

Stage I, %

NS 55 32 30 43 NS 42 40 38

NS 79 38‡ NS 57 NS NS NS 46

*NS ⫽ not stated. †Death within 30 days or same hospitalization. ‡Stage I/II combined. 736

Clinical Investigations

their review,4 225 octogenarians underwent surgical resection with a mortality of only 2.2%. Other series11,16,17 have also documented a mortality of ⬍ 5% in octogenarians undergoing anatomic resection for lung cancer. Elderly patients not treated with surgery may be offered either observation-only management or definitive radiation therapy. Unfortunately, no prospective studies exist that would define the outcome of these treatment modalities in the elderly. However, limited experience with observation alone for early stage lung cancer has been uniformly disappointing. For instance, a retrospective review of 49 patients with early-stage disease who either refused surgery or were considered inoperable due to medical comorbidities showed a median survival time of only 14 months.18 Similar results were reported in a metaanalysis of the patients enrolled in the Mayo, Hopkins, and Memorial trials for CT screening who did not receive surgical therapy for their stage I disease. In that analysis,19 only two patients who did not receive surgery were alive after 5 years. Results with definitive radiotherapy have also been poor. In a representative Japanese study,20 radiation in the elderly with stages I and II non-small cell lung cancer was well tolerated, but produced a 2-year and 5-year overall survival of only 40% and 16%, respectively. Other studies21,22 (which include younger patients) have confirmed an expected 5-year survival of only 10 to 20% after radiation therapy alone. While there are long-term survivors, the results are consistently inferior to surgical resection. Certainly, these retrospective studies cannot conclusively demonstrate the superiority of surgical resection over other therapies in the elderly. Patients in these studies who are medically inoperable may not be directly comparable to healthy octogenarians who are not offered or refuse surgery. Furthermore, the issue of quality of life following thoracotomy compared with radiation therapy has not been well studied in the elderly. Nonetheless, these studies do show that early stage lung cancer in the octogenarian is a fatal disease, and that the majority of deaths in this cohort will be related to progression of lung cancer rather than other causes. The current series shows that octogenarians can be successfully treated for lung cancer with surgical resection with a low overall major morbidity (13%) and mortality (1.6%). Postoperative cardiopulmonary complications were most frequent, especially dysrrhythmias. Pneumonia is the greatest threat to the octogenarian following lung surgery, as evidenced by the fact that four of our patients were reintubated for progressive pneumonia. Possible reasons for the low perioperative mortality in this series are strict patient selection, improvewww.chestjournal.org

ments in surgical and anesthetic technique, and attempts to avoid pneumonectomy whenever possible. Other series23 have shown significantly higher mortality in elderly patients undergoing pneumonectomy. We are extremely aggressive with postoperative pulmonary care including bronchoscopy, early ambulation, and physical therapy. Epidurals are routinely used for the first 3 postoperative days until chest tube removal. In addition, almost 50% of our octogenarians are transferred to an inpatient rehabilitation center for acute pulmonary rehabilitation. As in any retrospective analysis, we must also consider that a selection bias may play a role in our favorable results. The thoracic surgical service evaluated 79 octogenarians with lung cancer. Sixty-one patients underwent surgical resection, while 18 patients were deemed unresectable based on locally advanced disease (bulky N2, IIIB, or IV). While referring physicians may select octogenarians with minimal comorbidities and even early stage disease, when our series is compared to other reports we see a similar stage distribution, with 60 to 75% of resected octogenarians having stage I disease.10,24 Our experience demonstrates that octogenarians can undergo anatomic resection for lung cancer with an acceptable morbidity and a mortality that compares favorably with younger cohorts. The results also suggest that well selected octogenarians with a good performance status and stage IA disease can anticipate a long-term survival. The decision to offer resection to an octogenarian should therefore be based on meticulous clinical staging and cardiopulmonary performance rather than on age alone.

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Clinical Investigations