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Ann Thorac Surg 1999;68:2039-2043
© 1999 The Society of Thoracic Surgeons

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Original Articles: General Thoracic

Is there a role for pneumonectomy in pulmonary metastases?¹

^a Thoracic Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York, USA
^b Division of Thoracic Surgery, European Institute of Oncology, Milan, Italy

Address reprint requests to Dr Ginsberg, Thoracic Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10021
e-mail: ginsberr{at}mskcc.org

Presented at the Poster Session of the Thirty-fifth Annual Meeting of The Society of Thoracic Surgeons, San Antonio, TX, Jan 25–27, 1999.

Abstract

Background. Although sublobar and lobar resections are accepted operations for pulmonary metastases, pneumonectomy is viewed as a major incursion on Stage IV patients. We considered it important to ascertain the current results of pneumonectomy for pulmonary metastases since little information is available.

Methods. Of the 5,206 patients with pulmonary metastasectomy reported by the International Registry of Lung Metastases, 133 (3%) underwent primary, and 38 (1%) completion pneumonectomy between 1962 and 1994. Data were analyzed to determine the operative mortality rates, survival rates, and determinants of survival.

Results. Primary pneumonectomy was performed for metastatic disease mainly from epithelial (49%, 65 of 133) and sarcomatous (33%, 43 of 133) tumors. Indications were central lesion, eg, proximal endobronchial or hilar nodal metastases. Operative mortality was 4% (4 of 112) and a 5-year survival rate of 20% was achieved following complete resection (R0) in 112 patients. In contrast, the 21 incompletely resected patients had an operative mortality rate of 19% (4 of 21), and the majority did not survive beyond 2 years (p = 0.02). Survival was determined by the completeness of resection and not histology of the primary tumor, number of metastases, nodal status, and disease-free interval. In the 38 completion pneumonectomy patients, 35 were operated for recurrent disease and 3 for residual disease. Sarcomatous secondaries predominated in 28 patients. Complete resection was achieved in 31 patients (82%). The operative mortality rate was 3% (1 of 38 patients) and the 5-year survival rate was 30%.

Conclusions. Pneumonectomies for pulmonary metastases, albeit infrequently performed, were associated with acceptable operative mortality and long-term survival when performed in selected patients amenable to complete resection.

The earliest pneumonectomy for pulmonary metastasis was performed and reported in 1933 by Lilienthal [1], in the same year as the famed first successful pneumonectomy for carcinoma of the bronchus reported by Graham and Singer [2]. Unfortunately, Dr Lilienthal’s patient died of noncardiogenic pulmonary edema on the 4th postoperative day, and the diagnosis of a pulmonary metastasis was made when a primary uterine sarcoma was found at autopsy.

Until the early 1950s, pneumonectomy and lobectomy were the predominant resections performed for pulmonary metastases. In a series by Alexander and Haight, 10 (42%) of the patients had pneumonectomy and 12 (50%) had at least a lobectomy [3]. Seiler and colleagues, in 1950, reported 62 cases of pulmonary resection for metastatic disease to the lungs, 25 of which were pneumonectomies (40%) and 27 (44%) were lobectomies [4]. Lesser resections were performed in the remaining 10 cases. Increased use of chest roentgenograms in the follow-up of cancer patients led to the detection and ultimately resection of smaller, asymptomatic, peripheral pulmonary metastasis. It was recognized that more conservative resections appeared adequate and preserved normal lung. The ensuing decline of pneumonectomy for pulmonary metastasis was marked. In 1957, Gliedman and associates reported a pneumonectomy rate of 17% in 29 patients from the University of Minnesota, while the Mayo Clinic in 1965 reported a rate of 15% in 221 pulmonary metastasis resections performed on 205 patients [5, 6]. By the 1970s and 1980s, pneumonectomy rates decreased to below 10%. Memorial Hospital and M. D. Anderson had the most conservative rates of 4% and 6%, respectively [7, 8].

Although the operative risks and prognostic factors have been established for wedge resections [8–11], information on operative mortality and survival rates following pneumonectomy for pulmonary metastases is lacking. All current data were derived from single institutions’ experience based on subsets of fewer than 40 patients, reporting operative mortality rates of between 0% and 14% [6, 8, 12] and 5-year survival rates from 9% to 41% [3, 5, 12, 13]. The paucity of cases hampered any meaningful appraisal of pneumonectomy for pulmonary metastases, which prompted this report.

The International Registry of Lung Metastases (IRLM), launched in 1990, has reported on 5,206 patients with pulmonary metastasectomy, the largest series to date [9, 14]. It has accumulated substantial data on the indications and outcome of primary and completion pneumonectomies for pulmonary metastases.

Material and methods

Data was obtained from the IRLM, which has retrospectively chart reviewed 5,290 patients who underwent resection of pulmonary metastases with a curative intent. Details of the database set-up, patient accrual, inclusion and exclusion criteria, data collection, and the 18 members of the Registry are available from the initial publication [9]. Of the 5,206 evaluable patients, 133 (3%) patients underwent primary and 38 (1%) completion pneumonectomy for pulmonary metastases between 1962 and 1994. Completion pneumonectomy was defined as the last pulmonary resection in a sequence of unilateral pulmonary resections. Primary tumor control and absence of other distant metastasis were mandatory inclusion criteria.

Data on the indications for pneumonectomy, histologic types of the primary tumor, number of pulmonary metastases, presence or absence of nodal metastases, surgical approach, completeness of resection, disease-free interval (DFI), and survival were obtained, and univariate analysis was performed on patients who underwent primary pneumonectomy. Operative mortality was defined as deaths occurring within 30 days of pneumonectomy, and all deaths beyond 30 days but during the same hospitalization.

The IRLM has proposed four prognostic groups based on three clinical parameters, the resectability of the lesion, DFI (> 36 months), and number of metastases (> 1) [9]. This classification provided good prognostic stratification of all patients undergoing pulmonary metastasectomy. The patients who underwent primary pneumonectomy in this analysis were similarly grouped to determine the discriminant power of the proposed prognostic groups. Long-term survival was calculated from the time of pneumonectomy to the last date of follow-up or date of death and plotted using the Kaplan-Meier method. Log-rank tests were used to determine statistical significance.

Results

Primary pneumonectomy
Table 1 summarizes the study variables stratified by completeness of resection. One hundred and twelve (84%) patients underwent successful complete resection (R0), defined as the absence of macroscopic and microscopic residual disease following pneumonectomy. Incomplete resections with microscopic (R1) or macroscopic (R2) residual disease, occurred in the remaining 21 patients (16%). The predominant histology types were epithelial tumors (49%, 65 of 133), sarcomas (33%, 43 of 133), melanomas (11%, 14 of 133), and teratomas (7%, 9 of 133). The indication for pneumonectomy was central lesions, such as proximal endobronchial or hilar nodal metastases.

The majority of the primary pneumonectomies, 85 of 133 (64%), were performed for a single metastasis, whereas 28 (21%) had 2 to 3 metastases and 20 (15%) had 4 or more metastases. Mean maximum diameter was 6.3 cm for primary pneumonectomy compared to the smaller, 2.3 cm diameter, metastases for nonpneumonectomy patients [9]. Nodal metastases were present in 20% (26 of 133). The DFI was 0 to 11 months in 30 patients (23%), 12 to 35 months in 38 (29%), and more than 36 months in 63 patients (47%). Metastasectomy was performed most commonly through a unilateral approach (116 of 133, 87%), usually a posterolateral thoracotomy. Sixteen patients underwent the bilateral approach, ie, staged or clam-shell thoracotomy or median sternotomy with 10 performed for surgical access of the pulmonary metastases and 6 for wedge resections of contralateral lung metastases. Complete resection was performed in 5 and 4 patients, respectively.

There was no significant difference in the age, sex, histologic types, size of the lesion, and DFI between complete and incomplete resections. The number of metastases (p = 0.005) and the surgical approach (p = 0.002) differed significantly between the two groups.

The operative mortality rate following R0 resection in 112 patients was 4%, whereas the rate following incomplete resection was 19% (p = 0.02). In patients who underwent complete resection, their survival rates were 57%, 38%, and 20% at 1, 2, and 5 years, respectively. The corresponding 1- and 2-year survival rates following incomplete resection were 23% and 6%. All patients with incomplete resections died, 1 at 25 months and the rest within 2 years. The difference in survival between complete and incomplete primary pneumonectomy was highly significant with a log-rank ² of 5.53 (p = 0.02, Fig 1). Comparison of the 5-year survival rates following R0 resections between histologic types suggested relative improved survival (Table 2) for uterine, breast, renal, and teratomatous secondaries although no statistical significance was reached. Five-year survival following pneumonectomy for metastatic melanoma remained poor.

View larger version (19K): [in this window] [in a new window]   Fig 1. Survival of patients after R0 and R1 or R2 primary pneumonectomy.

View larger version (16K): [in this window] [in a new window]   Fig 2. Survival of patients by the number of resected metastases.

The operative mortality rate following completion pneumonectomy was 3% (1 patient) and the overall 5-year survival rate was 30%. Even for completion pneumonectomy, completeness of resection was an important prognostic factor, and survival of the 31 patients in whom complete resection was achieved was significantly superior to incomplete resection (median 29 vs 5 months, 30% vs 0 at 5 years; p = 0.001, log rank ² = 11.2) (Fig 3). When compared to primary pneumonectomy, completion pneumonectomy experienced better survival (median 29 vs 17 months, 30% vs 20% 5-year survival; p = 0.01, log rank ² = 9.9) (Fig 4).

View larger version (23K): [in this window] [in a new window]   Fig 3. Survival of patients following R0 and R1 or R2 completion pneumonectomy.

View larger version (22K): [in this window] [in a new window]   Fig 4. Survival of patients following primary and completion pneumonectomy.

Historically, pneumonectomy and lobectomy constituted more than 80% of all resections for pulmonary metastases [3, 4]. For the past 40 years, however, these resections have been replaced by lesser resections and, to date, pneumonectomy rates in major series are only between 3% and 6% [8, 9, 11]. Despite continuing efforts to conserve lung tissue, a centrally located metastasis may preclude any lesser resections. The relatively stabilized pneumonectomy rates over the last two decades attest to the continuing necessity for this infrequent procedure.

The indications for primary pneumonectomy in the treatment of pulmonary metastases have remained largely unchanged. Symptoms like intractable cough and hemoptysis occur in 15% to 20% of patients with pulmonary metastases and usually reflect disease in the central airway, often from an extrinsic compression or erosion into the tracheobronchial structures by parenchymal or nodal metastases [15]. True endobronchial metastasis, although less common, can occur from primaries in the colon, breast, and renal cancers, and rarely from thyroid carcinoma or malignant melanoma [16]. Central disease may appear on computed tomographic scans as an extraluminal hilar mass, endobronchial lesion, or less discretely as postobstructive atelectasis and pneumonitis. A meticulous flexible bronchoscopy is a mandatory endobronchial assessment for determining resectability in addition to providing histologic confirmation.

To date, no prospective data is available on pneumonectomy for pulmonary metastasis. Current literature is retrospective, based on the small number of patients or patients who would have undergone lesser resections today.

The reported operative mortality rates from various centers ranged from 0% to 14% [3, 6, 8, 11, 12, 13, 17]. The earliest experience for pulmonary metastasis resection from the University of Michigan and the Mayo Clinic reported no operative mortality [3, 6]. In 18 patients, McCormack and Martini, however, reported a single mortality attributed to a case of postoperative pneumonia, whereas Putnam and colleagues had a postoperative mortality rate of 11% in a series of 19 pneumonectomies [11, 12]. One patient died of hemorrhage following dissection around the pulmonary artery, which was encased by adhesions from multiple prior pulmonary resections. The other mortality was consequent to rapid progression of disease. The current operative mortality rate of 4% in our series following primary pneumonectomy for pulmonary metastasis is comparable to the recent series in the literature [18].

In Alexander and Haight’s early series, the median survival was 7.5 months (range: 6 months to 7 years) with 5-year survival rate of 20% [3]. This contrasted to Gliedman and coworkers’ collective review of 65 patients with pneumonectomy where the 5-year survival was 9% [5]. More recently, Putnam and associates reported 38 patients; half had synchronous resection of either chest wall or other intrathoracic structures and the remaining 19 underwent pneumonectomy alone [12]. In the latter group, complete resection was achieved in 84%. The median survival was 27 months and the 5-year survival rate was 21%.

The 20% 5-year survival rate after R0 resection better reflects the current survival following primary pneumonectomy for pulmonary metastases. This survival benefit and the acceptable operative mortality may be offered to selected patients with metastases requiring pneumonectomy and who have sufficient pulmonary reserve, controlled primary disease, no evidence of other metastatic disease, and lack better alternative therapy. Although it is lower than the 5-year survival rate of 36% for all pulmonary metastasectomies [9], it is superior to no resection. The survival data following pneumonectomy for pulmonary metastases may be unable to validate the prognostic groupings proposed by the registry due to the small number of patients.

In the Mayo Clinic series of completion pneumonectomy performed on 133 patients for a variety of benign and malignant causes, there was no operative mortality and a 5-year survival rate of 41% was achieved in 20 patients operated for pulmonary metastases. Information on completeness of resection, a current critical prognostic indicator, was not available from this series [13]. In contrast, Jensik and associates reported a mortality rate of 14% following completion pneumonectomy for recurrent lung cancer [19]. The respectably low 3% operative mortality rate and the surprising 30% 5-year survival rate in our series suggest that completion pneumonectomy may be offered to selected patients with recurrent disease confined to the ipsilateral lung. Survival of patients who underwent completion pneumonectomy was better than primary pneumonectomy and may be due to stricter selection criteria.

In conclusion, once offered with anecdotal survival benefit in the early 20th century, pneumonectomy (primary or completion) for pulmonary metastases has established curative benefits and no higher operative mortality than a similar resection for primary or recurrent non-small cell lung cancer. Given the lack of alternative established therapy, selected patients with isolated primary or recurrent pulmonary metastasis, and sufficient pulmonary reserve, may be offered primary or completion pneumonectomy. As an incomplete resection resulted in a much higher mortality and no long-term survival benefit, accurate selection of patients anticipated to have an R0 resection is crucial.

Footnotes

¹ For a listing of members of the International Registry of Lung Metastases, see the Appendix.

Appendix

The international registry of lung metastases
Belgium: Hôpital Erasme, ULB, Brussels; Canada: Mount Sinai Hospital, Toronto; England: Royal Brompton Hospital, London; France: Centre Marie Lannelongue, Paris; Hôpital Porte de Choisy, Paris; Germany: Rohrbach Clinic, Heidelberg; Thoraxchirurgie, Gerlingen; Italy: Instituto Nazionale Tumori, Milan; Universita La Sapienza and Tor Vergata, Rome; Ospedale Le Molinette Università di Torino, Turin; Patologia Chirurgica di Modena and Ospedale S. Orsola, Bologna; Universita "G. D’Annunzio," Chieti; The Netherlands: Daniel den Hoed Cancer Center, Rotterdam; Poland: Maria Sklodowska, Warsaw; United States: Memorial Sloan-Kettering Cancer Center, New York; The University of Texas M. D. Anderson Cancer Center, Houston; University of California, Los Angeles, California; National Cancer Institute, Bethesda, Maryland.

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