Surgical resection of isolated pulmonary metastases has been incorporated into the management of cancer for more than 70 years. However, many questions still remain concerning indications, technique, and efficacy for this approach. Patients with sarcomatous pulmonary metastases appear to benefit most from resection because of the unique biology of sarcomas, with their predilection for the lung as the only metastatic site. The paper by Drs. Kon and Martin provides a succinct and complete review of published outcomes for the treatment of patients with sarcomatous pulmonary metastases, including indications for surgery and a list of prognostic variables that affect survival after resection.
All physicians who treat these patients recognize the marked heterogeneity within the category of mesenchymal neoplasms. Some histologies, such as alveolar soft-part sarcoma, are fairly indolent, and patients with pulmonary metastases may survive for prolonged periods with observation of very slow-growing metastases. However, for most sarcomas, there are no available biomarkers to predict which patients will benefit from an aggressive therapeutic approach. Since resection remains the cornerstone of treatment for isolated pulmonary metastases, care of the patient with sarcomatous pulmonary metastases has evolved over the years to now include a larger group of patients who may benefit from metastasectomy.
The two most consistent prognostic factors for overall survival remain the disease-free interval (DFI) and the number of pulmonary nodules. The one consistent factor in all series is that only patients in whom a complete (R0) resection is achieved have a longer survival following surgery. In our experience, incomplete resection is not beneficial. In many series, the number of nodules is no longer a factor determining survival if complete resection can be achieved. We also have observed that progression after chemotherapy is a novel predictor of poor outcome after pulmonary metastasectomy. Other significant predictors of better survival include favorable tumor histology, low histologic grade, and age less than 50 years. Repeated metastasectomy , when the patient has adequate pulmonary reserve, is often beneficial. Previously, extrapulmonary metastases have been considered a disqualifier for resection. We no longer view these as a contraindication, as long as the extrapulmonary disease can be completely resected.
In our practice, patients are typically referred for immediate surgery if they present with a single pulmonary metastasis or have a limited number of metastases and a long DFI. Those who present with synchronous metastases or who develop metastatic disease early with multiple pulmonary nodules are treated initially with chemotherapy to determine the pace of disease progression on treatment. Patients who respond to chemotherapy, those with stable disease, and those with slow progression are referred for resection, while those with rapidly progressing metastatic disease receive alternative chemotherapy treatment. Chemotherapy is continued in the adjuvant setting only if there is evidence of clinical benefit from preoperative chemotherapy.
Computed tomography (CT) scanning is routinely performed to monitor disease progression. The surgical approach should be individualized. As imaging improves our ability to localize smaller nodules, less invasive options become more appealing and may facilitate repeat metastasectomy. Stereotactic body radiation therapy, also called stereotactic ablative radiation therapy (SABR), has been used to treat patients with three or fewer pulmonary metastases. Although follow-up on the average has been less than 2 years, local control appears to be equivalent to that achieved with surgery. However, it is common for imaging studies to underestimate the number of pulmonary metastases. Thus, a potential disadvantage of this technique is an inability to evaluate the entire lung. However, the lung preservation achieved by SABR may be important in patients who have had previous resections or who have compromised pulmonary function. More prospective studies are needed to evaluate this modality. Clinical lack of equipoise may prevent randomized metastasectomy trials from being conducted.
The more than 50 histologic subclassifications of sarcoma, the heterogeneous outcomes, and the rarity of these tumors make the design of randomized clinical trials difficult. Those patients who present with extremely slow-growing disease (for example, extraskeletal myxoid chondrosarcoma) and those with more aggressive, rapidly progressing tumors (eg, synovial cell sarcoma) would require stratification in a random allocation clinical trial. However, the small numbers of patients in each group would not make this a practical trial design.
Molecular analysis of sarcomas to identify gene signatures predictive of prognosis and response to systemic therapy would be useful. The combination of drugs targeted to specific oncogenic driver mutations and resection of oligometastatic disease should be explored. A better understanding of the biology of the tumor and the development of histologic-specific nomograms may ultimately improve our ability to select patients for metastasectomy. As systemic therapy improves, treatment of local residual oligometastatic disease will become an increasingly important consideration.
Financial Disclosure: The authors have no significant financial interest or other relationship with the manufacturers of any products or providers of any service mentioned in this article.
1. Stephens EH, Blackmon SH, Correa AM, et al. Progression after chemotherapy is a novel predictor of poor outcomes after pulmonary metastasectomy in sarcoma patients. J Am Coll Surg. 2011;212:821-6.
2. Blackmon SH, Shah N, Roth JA, et al. Resection of pulmonary and extrapulmonary sarcomatous metastases is associated with long-term survival. Ann Thorac Surg. 2009;88:877-84; discussion 884-5.