Pulmonary metastasectomy has evolved into a widely accepted and successful treatment strategy for patients with advanced disease of various tumor types. The growth of this surgical practice reflects the frequency in which the metastatic focus resides in the lung.¹ Initial reports represented the findings of retrospective case series and large, registry data which did not provide any true understanding of the impact of surgical intervention in patients presenting with advanced, metastatic disease.^2,3 Accordingly, the paradigm shift from primary medical management of distant disease to operative intervention was slow to gain momentum as early results failed to show consistent improvement in survival outcomes. Diagnostic imaging modalities and surgical technique have continued to improve over the past two to three decades, however, affording select patients with aggressive cancers (e.g., primary colorectal, soft tissue, and genitourinary tumors) substantial benefit from pulmonary resection for metastatic lesions. In this chapter, we will focus on soft tissue and abdominal malignancies that commonly metastasize to the lung and will structure our discussion to be of highest value for those within the surgical field.

Preoperative Imaging

It is important to evaluate a new pulmonary nodule in the context of the patient’s oncologic history as it could represent a benign finding, new primary process, or metastatic disease—the rate of the latter increasing substantially depending on the histologic subtype of the primary tumor. For example, patients with melanoma or sarcoma are 10 times more likely to have metastatic disease than a second primary if a new pulmonary nodule is diagnosed. Similarly, in patients with colonic or genitourinary cancers, a nodule represents metastatic disease nearly 50% of the time.⁴ Accordingly, the preoperative evaluation must be tailored to the patient’s unique situation and a high degree of suspicion maintained in specific cases.

Prior to embarking upon surgery, a series of diagnostic studies should be obtained to further characterize the disease and its resectability. Per the European Society of Thoracic Surgeons (ESTS) Lung Metastasectomy Project, the following conclusions regarding appropriate imaging emerged after an extensive review of the literature⁵:

1. 
   

   Helical computed tomography (CT) of the chest with a minimum of 3- to 5-mm slick thicknesses should be obtained. There are no current data advocating for the application of 64-, 128- or 256-slice CT scanners.

   
   
2. 
   

   Given the risk of disease progression, recent imaging within 4 weeks of the planned metastasectomy is strongly recommended.

   
   
3. 
   

   If positron emission tomography is available at the surgical center, it is recommended that it be employed, especially in patients with PET-avid primary lesions. This will help to identify extrathoracic foci of disease.

   
   
4. 
   

   A baseline image should be obtained 4 to 6 weeks following metastasectomy. Additional images should be obtained at regular, 6-month intervals for the first 2 years, after which the interval can be lengthened to yearly for at least 5 years following the resection.

Pulmonary Function Tests

In order to determine what degree of pulmonary resection an individual can tolerate, it is important to appreciate the expected degree of decline in pulmonary function with the various extents of surgical intervention. With complete pneumonectomy, the forced expiratory volume in 1 second (FEV1) drops between 34% and 36%, the forced vital capacity (FVC) 36% to 40%, and the maximum oxygen consumption (VO₂ max) 20% to 28%.^6,7 With lobectomy, the reduction in the expected values is less drastic—FEV1 by 9% to 17%, FVC by 7% to 11%, and VO₂ max 0% to 13%.^6,7 A plethora of sources have established that patients with an FEV1 >2 can safely tolerate a pneumonectomy and those with an FEV1 >1.5  L can endure a lobectomy.

The importance of referencing these studies and understanding their implications cannot be marginalized. Before considering a surgical resection, the surgeon and/or the internist should always evaluate at least the FEV1 and DLCO to determine whether or not the patient will have enough pulmonary reserve after the operation to adequately oxygenate and ventilate. Once a metastatic process has been diagnosed, appropriate patients should be considered for surgical resection. It has been widely accepted that this aggressive strategy should only be pursued in patients who have already undergone a successful R0 resection of their primary lesion, with isolated pulmonary metastasis(es) or extrathoracic lesions amenable to resection and with medical clearance to tolerate a potentially major pulmonary resection.

Lymph Node Sampling

Currently, it is standard surgical practice to perform a nodal sampling in cases of pulmonary resection for primary disease. In a large registry of 5206 patients with pulmonary metastases, there was only a 5% documented incidence of lymph node involvement.² It is important to note, however, that lymph node dissection was only executed in 4.6% of patients in that study.² In a more recent, albeit smaller series, of 70 patients with stage IV disease with pulmonary lesions who underwent mediastinal lymphadenectomies, metastasis was diagnosed in 28.6% (20).⁸ A similar incidence was demonstrated in large study of merged series of sarcoma and melanoma patients from 1985 to 2005 in which thoracic lymph node involvement was identified in a weighted average of 22% of the cohort.⁹ In a survey of thoracic surgeons regarding their personal practice of mediastinal lymph node harvest, only 3.4% indicated that they routinely use mediastinoscopy to sample the nodal basin in comparison to 24% that never utilize this modality prior to pulmonary metastasectomy.¹⁰ The same survey also demonstrated that formal mediastinal lymphadenectomy was only performed by 13% of the respondents, whereas limited sampling was practiced by 55.5%.¹⁰ This was despite the American College of Surgeons Oncology Group’s randomized prospective trial which established the safety of this intraoperative adjunct.¹¹

It remains unclear if nodal dissection is therapeutic or merely diagnostic, but institutional series have identified the presence of disease as a prognostic indicator⁸ and others have revealed a survival difference after stratification by “N” stages.^12,13 Regardless, given the thoracic surgeon’s familiarity with mediastinal exploration, we universally advocate for the intraoperative assessment of this nodal basin.

Extent of Surgical Resection

The extent of resection is dictated by the ability to perform an R0 operation while simultaneously preserving as much functional lung parenchyma as possible. In the aforementioned ESTS survey, most respondents (about 70%) considered the need for a pneumonectomy to be a relative contraindication for proceeding with metastasectomy.¹⁰ This reservation is undoubtedly influenced by the consistently high operative and short-term mortalities reported in several small series.^2,14,15 More recently, however, institutions have demonstrated acceptable long-term survival,¹⁶ supporting the implementation of strict selection criteria for patients that might tolerate a pneumonectomy, including: (1) a centrally located, solitary lesion, (2) a long disease-free interval between resection of the primary and subsequent metastasectomy, and (3) no previous pulmonary resection.

Surgical Approach

Once the necessary preoperative staging and pulmonary evaluation have been completed, it then becomes the responsibility of the surgeon to select the most appropriate operation for the patient based on his/her comorbidities as well as the location of the tumor and the difficulty level of the surgical resection. The historically preferred approach for metastasectomy of the lung involved bilateral posterior-lateral thoracotomy incisions. This would permit the surgeon full access to palpate all lobes of the lung for disease that may not have been appreciated during preoperative imaging.¹⁷ In the mid-1980s, with the surge in the field of cardiac surgery, thoracic surgeons began to employ a midline sternotomy for pulmonary metastasectomy. While it provided excellent exposure to most of the lung in a bilateral fashion, it proved insufficient for visualization and resection of the posterior segments.¹⁷ Other approaches include: (a) anterior bilateral sternothoracotomy (clamshell) incision to access both lungs which results in a more cosmetically appealing incision, for women particularly; (b) muscle sparing thoracotomies; (c) anterior thoracotomy; or (d) hybrid combination of the above as well as minimally invasive approaches discussed below.

Lung-sparing resections are generally favored. Wedge resection with a grossly negative margin is the primary goal. Occasionally in order to get to a deeply seated nodule, a formal anatomic resection (segmentectomy or lobectomy) is required, but should be avoided if possible. If multiple small (<1  cm) peripheral nodules are resected, use of the cautery excision technique of only the nodule can be used, preserving normal lung parenchyma.

The dictum of manually exploring both lungs intraoperatively was questioned by Roth et al in the late 1980s, however, and their findings necessitated a change in the course of pulmonary resection.¹⁷ As manual manipulation of the lung parenchyma became less crucial, the idea of minimally invasive surgery in the chest cavity gained momentum. There has been rich experience in other fields of surgery showing equivalent if not improved results in minimally invasive procedures in comparison to more traditional open approaches.^18–20 Some researchers have postulated that this is partly due to the relative immunosuppression associated with open surgery, which is especially critical in the context of oncological resections due to the important role that peripheral blood mononuclear cells play in tumor surveillance.^21,22 By evaluating perioperative cytokine and inflammatory marker levels, researchers have noted a significant increase in these cells in minimally invasive surgery in comparison to conventional open resections.²³ This has the potential to translate into survival benefits as these cells could be advantageous in scavenging any residual or micrometastatic disease not excised at the time of surgery.²⁴

While there are undisputed benefits of video-assisted thoracic surgery (VATS), a review of the NSQIP database demonstrated that only 26% of resections are performed in a minimally invasive manner.²⁵ This is discouraging given that the same study showed that those undergoing an open thoracotomy had an increased risk of pneumonia, unplanned reintubation, sepsis/shock, and a longer median length of stay.²⁵ A decrease in these comorbid factors is not surprising but other studies have even showed a yearly survival benefit with VATS lobectomy/segmentectomy.²⁶

A study in Japan of over 300 patients who underwent VATS lobectomy for primary cancer of the lung demonstrated survival benefits comparable to that of open surgery.²⁷ Similarly, a prospective trial of 100 patients undergoing resection for stage IA (T1N0M0) disease who were randomized to either conventional open or video-assisted surgery found similar 5-year survivals (85% vs. 90%, respectively) between the two groups.²⁸ Due to the limited sample sizes in these studies, a more comprehensive review of randomized and nonrandomized trials was necessary to evaluate the safety and efficacy of VATS versus open surgery for pulmonary disease.

In addition to the question concerning the ability to obtain an equivalent oncologic resection, there has been speculation that VATS might not provide an adequate lymphadenectomy. This hypothesis, however, has not been supported by the medical literature. An analysis of the National Comprehensive Cancer Network’s (NCCN) non-small cell lung cancer (NSCLC) database illustrated that mediastinal lymph node assessment was equally successful in VATS when compared to traditional thoracotomy.²⁹ This is paramount as lymph node evaluation is not only crucial in the staging of lung cancer, but also in predicting survival after surgery.

The aforementioned advantages of minimally invasive surgery are rather straightforward and expected. Another subtler discovery by researchers at Duke University, however, could have equally profound implications. Given the findings of a handful of randomized controlled trials over the past 5 to 10 years, it is now accepted that adjuvant chemoradiation therapy improves the overall survival in patients with NSCLC.^30,31 It has demonstrated that this benefit is further amplified in patients who underwent VATS lobectomy as compared to traditional thoracotomy.³² In a study of 100 patients, almost equally divided between VATS lobectomy (n = 57) and resection via conventional thoracotomy (n = 43), chemotherapy compliance was higher in the former.³² The VATS arm had substantially fewer delayed (18% vs. 58%) and reduced (26% vs. 49%) doses as well as a greater overall percentage of their planned chemotherapy regimen administered.¹⁸ While these findings are not surprising given the morbidity associated with a posterior-lateral thoracotomy incision, they will most likely have considerable survival benefits.

There is a slowly increasing body of literature using alternative local therapies other than surgery. These include stereotactic body radiation therapy (SBRT) and radiofrequency ablation (RFA). Currently the data are limited focusing on pulmonary metastases, and some of it is intermixed with primary carcinomas. Though surgery remains the gold standard if resection is possible, these alternative therapies can be considered if the patient’s condition or pulmonary function precludes surgery, or the patient’s desire not to proceed with an operative approach. However, certain tumors such as osteosarcomas may be difficult to access via RFA due to the calcified composition. It is common these days to discuss these difficult patients in a multidisciplinary fashion, or even offer hybrid approaches involving both surgery and SBRT/RFA.

Complete resection of all pulmonary nodules yields the optimal surgical results in long-term survival. Thus, proper patient selection is essential and predicts a successful outcome. The 1997 report from the International Registry of Lung Metastasis (IRLM) consortium defined in multivariate analysis the prognostic factors influencing survival for the different tumor systems.² Disease-free interval, number of metastases, and tumor type were highly significant independent prognostic variables at univariate as well as multivariate analysis. However, the achievement of a macroscopically complete resection was the most important independent prognostic factor. From this analysis, a novel classification was proposed (Table 62-1), combining these three prognostic indicators (disease-free interval, number, and radicality of resection).

Survival and recurrence is dependent on the cell type of the primary tumor and the extent of pulmonary involvement. From the IRLM registry, 53% of patient’s disease recurred after complete lung metastasectomy, with a median time to recurrence of 10 months.² Survival was best for epithelial and germ cell tumors, and worst for sarcoma and melanoma metastases. The registry results are summarized in Table 62-2. For patients undergoing a second metastasectomy, survival was 44% at 5 years and 29% at 10 years, a little lower from that seen after initial metastasectomy. It is stressed however, that surgery may be the only optimal treatment modality compared to chemotherapy. Similar favorable results have been reported in colorectal cancer after repeated liver, or liver and lung, salvage metastasectomy.