Patient Selection/Preoperative Evaluation
Most patients are asymptomatic at presentation, with pulmonary metastatic disease found on routine surveillance imaging. In the fewer than 10% of patients who do present with symptoms, the most frequent complaints are hemoptysis, spontaneous pneumothorax, postobstructive pneumonia, and cough. In these patients, strong consideration should be given to surgical intervention even if it is of more palliative than curative intent.
Not all patients with sarcomatous pulmonary metastases will benefit from resection. Identification of negative prognostic variables through an appropriate history taking and adjunctive testing is essential. Generally, to be considered a candidate for resection, the primary tumor must be controlled, there must be no other distant unresectable disease, and it must be possible to achieve complete resection of the metastatic burden. There are, therefore, several key questions to ask when evaluating a patient for metastasectomy (Table 1):
1. Is the primary site controlled?
An unresectable, or an incomplete (R2) resection of the primary tumor is generally considered a contraindication to pulmonary metastasectomy. Similarly, local recurrence should be addressed successfully before embarking on resection of metastatic lesions.
2. Is there other distant extrapulmonary disease?
Although there are no large studies evaluating this question, Blackmon et al showed that if the distant disease can be sequentially or synchronously resected, outcomes similar to those seen with only pulmonary metastases can be achieved. This remains an area of controversy. However, given the generally young, fit patient population who present with extremity sarcomas, an aggressive approach is often warranted.
3. What is the disease-free interval?
The disease-free interval (DFI) refers to the time from complete resection of the primary tumor to the diagnosis of metastases. DFI has been shown repeatedly to be an important prognostic factor. In the International Lung Metastases Registry, the cutoff point for a favorable DFI was 36 months. However, there is no consensus regarding a minimal DFI prior to pulmonary metastasectomy. In fact, synchronous presentation of both a primary sarcoma and lung lesions is not a contraindication to metastasectomy, presuming all gross disease can be resected in a staged fashion; however, such a presentation portends more aggressive tumor biology, and this should be taken into consideration in a patient who may be a marginal candidate for surgery. Additionally, for patients with synchronous disease or a short DFI, the use of systemic therapy prior to metastasectomy should be discussed in a multidisciplinary setting. This builds in a period of observation to determine whether the tumor is progressing rapidly and will be widely metastatic in a period of weeks to months, in which case the patient would not benefit from pulmonary resection.
4. Can the metastases be completely resected and the patient still be left with adequate pulmonary reserve?
Pulmonary function tests are mandatory prior to lung surgery, and the usual guidelines for operability should be followed. Depending on age and comorbidities, cardiac testing may be appropriate as well. Removing two or three small peripheral nodules by wedge resection will have little impact on respiratory function status in most patients. A parenchyma-sparing approach is always preferred, especially given the frequency of recurrent disease in the lungs, often warranting multiple lung resections over several years. Anatomic resections, especially pneumonectomy, should be reserved for cases in which no other option for complete resection exists. Surgery is contraindicated when there is invasion of unresectable structures, or if all gross disease cannot be removed (eg, miliary disease). Ideal characteristics that allow maximal lung-sparing surgery include: unilateral and peripheral location, small tumor size, and a limited number of metastases. In contrast, large tumors, central masses, or miliary disease would be less likely to result in adequate postoperative pulmonary function (Figure 3).
5. Are there equally effective systemic therapies?
There are no randomized studies comparing the effectiveness of chemotherapy to metastasectomy in sarcoma. Because all of these patients are by definition stage IV, consideration of systemic chemotherapy is recommended. This is particularly important in patients with high-grade histology and aggressive tumors. Doxorubicin(Drug information on doxorubicin) and ifosfamide(Drug information on ifosfamide) have become the chemotherapeutics of choice for adjuvant therapy in metatstatic soft-tissue sarcoma, which may explain the improved outcomes seen with metastasectomy over the past decade. However, controversy still remains; several studies have shown no benefit for chemotherapy, and one study has indicated that it is not cost-effective compared with metastasectomy. For patients with osteogenic sarcoma or alveolar soft parts sarcoma, in which systemic therapies are known to be less effective—and in patients who may not tolerate chemotherapy toxicities—metastasectomy may be a particularly useful alternative.
Preoperative pulmonary function testing and assessment of functional status are vital to determining how much lung can safely be resected. If there is concern, a quantitative pulmonary perfusion scan may be of benefit and often is necessary with repeat resections. Patients treated with bleomycin(Drug information on bleomycin) may be at higher risk for postoperative acute respiratory distress syndrome (ARDS) and pulmonary fibrosis and thus warrant more careful evaluation. Cardiac testing should be considered based on age and comorbidities; in addition, adriamycin cardiotoxicity can be of concern regardless of age. A CT scan of the chest with fine cuts and IV contrast should be obtained on all patients to assess the number, size, and location of the pulmonary metastases. Positron emission tomography (PET)/CT scans are frequently performed in cancer patients, but their routine use in the evaluation of sarcoma is controversial. A retrospective review of patients evaluated at the Mayo Clinic found that PET scans were only positive for 44% of malignant nodules in patients with sarcoma, making the utility of such scans in this group questionable. However, another study indicated that PET/CT scans altered management in 14% of all oncologic patients under consideration for lung resection for metastatic disease, perhaps by identifying other, unsuspected sites of disease. In our experience, many patients are referred for surgery after they have already had a PET/CT scan. If a PET/CT scan has not been done, it is up to the discretion of the surgeon whether or not to obtain one. In any patient with neurologic symptoms, a brain magnetic resonance imaging (MRI) scan should be obtained. Finally, flexible bronchoscopy is an important step before lung resection commences, since occult endobronchial disease has been reported in up to 3% of patients.