For decades, surgical resection of pulmonary metastases has been performed; despite limited randomized data, surgery is increasingly accepted as an integral part in the management of metastatic disease. Long-term results indicate resection is potentially curative with significantly improved survival following complete resection. Recurrence, however, is not uncommon with many patients undergoing repeat resection. With advancing surgical technique and adjuvant therapies, patients with high or recurrent tumor burden are increasingly afforded disease control and potential cure. In this review, the prognostic characteristics of pulmonary metastases from sarcoma, preoperative evaluation, operative technique, long-term outcomes, and management of complex patients are highlighted.
Key points
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Sarcoma is a rare, heterogeneous disease with a common propensity to metastasize to the lungs.
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With careful patient selection, pulmonary metastasectomy improves survival when compared with historical controls.
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Many favorable prognostic factors have been identified, including long disease-free interval and complete (R0) resection.
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Video-assisted thoracoscopic surgery is increasingly used in highly select patients with favorable prognostic characteristics.
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Extensive resection for large or recurrent metastatic sarcomas can be safely performed in some patients.
Introduction
Sarcoma comprises a heterogeneous group of histologic subtypes with a propensity to metastasize to the lungs. Isolated pulmonary metastases occur in as many as 20% of patients diagnosed with soft tissue sarcoma and as many as 40% in those with a primary bone sarcoma. Although historically pulmonary metastasis represented advanced disease and the need for palliation, surgical resection for control of disease burden has become a mainstay of therapy and a potentially curative option for those with resectable pulmonary metastasis. The role for surgery continues to evolve with the introduction of adjunctive therapies, including radiofrequency ablation; advanced radiation therapy, such as stereotactic body radiation therapy (SBRT); and complex salvage operations. These advances have driven the need for complex multidisciplinary care, particularly with the inclusion of a thoracic surgeon. Resection of metastatic pulmonary sarcoma has been reported since the late 1800s; however, the first isolated resection of metastatic foci occurred in 1926 by Divis. Despite this, there have been no published randomized controlled trials comparing surgery with systemic therapy or radiation for metastatic sarcoma, though significant research, particularly with the formation of the International Registry of Lung Metastases (IRLM), indicates that pulmonary metastasectomy (PM), when it can be performed, is associated with improved outcomes.
Many of the original reports of PM for sarcoma were small case series pointing toward improved overall survival with resection in eligible patients when compared with historical controls. For example, one center noted a high incidence of patients with osteosarcoma developing lung metastases follow extremity amputation. A system for iterative complete surgical resection of pulmonary metastases in these patients was developed, with some patients requiring up to 9 thoracotomies. Five-year survival in this center’s cohort significantly increased from 0% to 32%.
The IRLM was formed in the 1990s as a consortium of high-volume centers performing PM for a variety of malignancies, including sarcoma. In a long-term follow-up study from the IRLM, 5206 patients underwent metastasectomy with 42% having sarcoma as the primary tumor. Most patients underwent open thoracotomy or sternotomy and had an overall survival of 31% at 5 years and 26% at 10 years. Patients with sarcoma, however, were more likely to recur (64%) as opposed to those with epithelial (46%) or germ cell (26%) metastases. Favorable outcomes were reported in those with a longer disease-free interval (DFI), small number of nodules, and complete resection.
Guidelines for physicians and surgeons in the treatment of metastatic pulmonary sarcoma have been proposed dating back to Ehrenhaft and colleagues in 1958; however, the lack of randomized controlled trials has limited their overall utility. Rusch and colleagues concluded that patients should meet the following criteria: control of the primary tumor; ability to resect metastatic disease completely; ability of patients to tolerate pulmonary resection; absence of extrathoracic metastases; and absence of better alternative systemic therapies. The indications for resection of metastatic sarcoma to the lung continue to evolve as more studies examine the use of minimally invasive surgery, the utility of aggressive resections, and alternate therapies, such as SBRT.
In this article, the authors review the prognostic factors associated with improved survival following pulmonary metastasectomy for sarcoma, preoperative evaluation, surgical techniques and management, long-term follow-up, and the complex management of large tumors and recurrent disease.
Introduction
Sarcoma comprises a heterogeneous group of histologic subtypes with a propensity to metastasize to the lungs. Isolated pulmonary metastases occur in as many as 20% of patients diagnosed with soft tissue sarcoma and as many as 40% in those with a primary bone sarcoma. Although historically pulmonary metastasis represented advanced disease and the need for palliation, surgical resection for control of disease burden has become a mainstay of therapy and a potentially curative option for those with resectable pulmonary metastasis. The role for surgery continues to evolve with the introduction of adjunctive therapies, including radiofrequency ablation; advanced radiation therapy, such as stereotactic body radiation therapy (SBRT); and complex salvage operations. These advances have driven the need for complex multidisciplinary care, particularly with the inclusion of a thoracic surgeon. Resection of metastatic pulmonary sarcoma has been reported since the late 1800s; however, the first isolated resection of metastatic foci occurred in 1926 by Divis. Despite this, there have been no published randomized controlled trials comparing surgery with systemic therapy or radiation for metastatic sarcoma, though significant research, particularly with the formation of the International Registry of Lung Metastases (IRLM), indicates that pulmonary metastasectomy (PM), when it can be performed, is associated with improved outcomes.
Many of the original reports of PM for sarcoma were small case series pointing toward improved overall survival with resection in eligible patients when compared with historical controls. For example, one center noted a high incidence of patients with osteosarcoma developing lung metastases follow extremity amputation. A system for iterative complete surgical resection of pulmonary metastases in these patients was developed, with some patients requiring up to 9 thoracotomies. Five-year survival in this center’s cohort significantly increased from 0% to 32%.
The IRLM was formed in the 1990s as a consortium of high-volume centers performing PM for a variety of malignancies, including sarcoma. In a long-term follow-up study from the IRLM, 5206 patients underwent metastasectomy with 42% having sarcoma as the primary tumor. Most patients underwent open thoracotomy or sternotomy and had an overall survival of 31% at 5 years and 26% at 10 years. Patients with sarcoma, however, were more likely to recur (64%) as opposed to those with epithelial (46%) or germ cell (26%) metastases. Favorable outcomes were reported in those with a longer disease-free interval (DFI), small number of nodules, and complete resection.
Guidelines for physicians and surgeons in the treatment of metastatic pulmonary sarcoma have been proposed dating back to Ehrenhaft and colleagues in 1958; however, the lack of randomized controlled trials has limited their overall utility. Rusch and colleagues concluded that patients should meet the following criteria: control of the primary tumor; ability to resect metastatic disease completely; ability of patients to tolerate pulmonary resection; absence of extrathoracic metastases; and absence of better alternative systemic therapies. The indications for resection of metastatic sarcoma to the lung continue to evolve as more studies examine the use of minimally invasive surgery, the utility of aggressive resections, and alternate therapies, such as SBRT.
In this article, the authors review the prognostic factors associated with improved survival following pulmonary metastasectomy for sarcoma, preoperative evaluation, surgical techniques and management, long-term follow-up, and the complex management of large tumors and recurrent disease.
Prognostic factors
Although the primary source of sarcoma may be highly variable and includes both indolent and aggressive subtypes, several characteristics have been identified to inform patients’ prognosis and treatment plan. It is again important to note that these characteristics have largely been identified based on single-center, retrospective reviews that, although generally consistent, may be subject to bias from the pathologic heterogeneity of sarcomas, multiple adjuvant therapies involved, and careful case selection by surgeons. In addition, although the characteristics may be useful in guiding the surgeon as well as the rest of the multidisciplinary team, they do not preclude patients from undergoing PM, especially in those with limited disease. With this in mind, many of the prognostic factors characterized include the histology of the primary sarcoma, DFI, number of lesions in the lung, a surgeon’s ability to obtain a complete resection, the responsiveness to chemotherapy, and lymph node status. A summary of recent articles examining some of these factors can be found in Table 1 .
| Study | Sample Size | Histologic Subset a | OS | DFI | Completeness of Resection b | Preoperative chemotherapy | VATS (%) |
|---|---|---|---|---|---|---|---|
| Dossett et al, 2015 | 120 |
| 5-y survival: 44% | MOS <12 mo: 43 mo MOS >12 mo: 93 mo ( P = .004) | R0 MOS: 29.6 mo R1/2 MOS: 6.3 mo ( P = .002) | 22% | 63 |
| Blackmon et al, 2009 | 234 |
| 5-y survival: 26% | N/A | N/A | 100% | 1.7 |
| Smith et al, 2009 | 94 |
| 5-y survival: 15% | MOS <25 mo: 13.5 mo MOS >25 mo: 32 mo ( P = .001) | R0 MOS: 22 mo R1 MOS: 11.5 mo ( P <.0001) | MOS yes: 12 mo MOS no: 16 mo ( P = .2) | N/A |
| Gossot et al, 2009 | 113 |
| 5-y survival: 52.5% | N/A | N/A | N/A | 27.4 |
| Reza et al, 2014 | 145 |
| 5-y survival: 42% | Mean DFI 30.4 ± 39.4 mo | 5-y OS R0: 42% | 77.1% | 25.5 |
| Kim et al, 2011 | 97 |
| 5-y survival: 50.1% | 5-y OS <12 mo: 21% 5-y OS >12 mo: 65% ( P <.0001) | 5-y OS R0: 54% ( P = .004) | N/A | 18.6 |
| Mizuno et al, 2013 | 52 |
| 5-y survival: 50.9% | 5-y OS <12 mo: 17.2% 5-y OS >12 mo: 38.3% ( P = .003) | 5-y OS R0: 54.2% ( P <.001) | N/A | 59 |
| Garcia Franco et al, 2010 | 52 |
| 5-y survival: 31% | 5-y OS <20 mo: ∼20% 5-y OS >20 mo: ∼42% ( P = .03) | N/A | N/A | 19 |
| Raciborska et al, 2015 | 38 | Ewing sarcoma (100%) | 3-y survival: 60.7% | N/A | N/A | 100% | 0 |
a Three most common histologic subtypes.
b R0 is equivalent to complete resection or negative margins.
Histology
Nearly 100 different histologic subtypes of sarcoma with varying grades of differentiation have been identified. Sarcoma is generally divided into the broad categories of soft tissue and primary bone with undifferentiated pleomorphic sarcoma and primary bone being the most likely to metastasize to the lung. Among soft tissue sarcomas, undifferentiated pleomorphic sarcoma (formerly malignant fibrous histiocytoma) is the most common histology (25%), followed by leiomyosarcoma (18%), synovial sarcoma (10%), and liposarcoma (10%). Similar to osteosarcoma, soft tissue sarcomas arising on the extremities are more likely to metastasize to the lung than those arising from the viscera. There is also an increase in frequency of metastasis associated with increasing histologic grade. Survival varies widely in accordance with the many different histologic subtypes. Blackmon and colleagues demonstrated a median survival following resection for osteosarcoma, malignant fibrous histiocytoma, synovial sarcoma, and leiomyosarcoma as 28.9, 16.7, 30.2, and 41.8 months, respectively.
Disease-Free Interval
DFI is defined as the time from the treatment of the primary lesion to the development of pulmonary metastases. DFI has been a clear prognostic indicator for many years and in nearly all studies. The IRLM showed that patients (including all primary sources of tumor) with a DFI of 0 to 11 months had a median survival of 29 months as opposed to patients with a DFI greater than 36 months when the median survival is 49 months. In a recent retrospective review of 120 patients with pulmonary metastases specifically from sarcoma, Dosset and colleagues confirmed the results of the IRLM ( Fig. 1 ).
Related posts:
Contemporary Management and Controversies of Sarcoma
Refinements in Sarcoma Classification in the Current 2013 World Health Organization Classification of Tumours of Soft Tissue and Bone
Sarcomas 2016
Sarcomas of the Breast with a Spotlight on Angiosarcoma and Cystosarcoma Phyllodes
Combined Therapy of Gastrointestinal Stromal Tumors
Myxofibrosarcoma
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