The recognition of pulmonary metastases from an extrathoracic primary tumor is a dramatic and emotional change in the care of the cancer patient. The clinical situation immediately changes from potential cure to the tacit acknowledgment of probable incurability. Goals of therapy change from living without evidence of disease to living, and living well, with systemic disease. We believe that pulmonary metastasectomy in carefully selected patients contributes to quality of life and may give the patient extended periods of time without obvious disease.

Many primary tumors metastasize to specific target organs.¹ In the 1930s, it was noted that patients dying of pulmonary metastases frequently failed to exhibit extrapulmonary disease at autopsy.² As a result, several surgeons felt that it would be reasonable to offer surgical resection of these lesions in the hope of prolonging survival. The first reported pulmonary metastasectomy removed a single renal cell metastasis in 1930, and the patient lived for two more decades.³ Interest in this surgical approach was increased with the development of systemic adjuvant chemotherapy, which appeared to increase survival.

The role of surgical resection of metastatic disease, however, is not universally accepted in the nonsurgical community. No randomized trial has been constructed to establish a survival advantage of pulmonary metastasectomy. In fact, the multitude of variables that would have to be included in the eligibility criteria (e.g., number of metastases, cell type, disease-free interval [DFI], cardiorespiratory reserve) makes it unlikely that a randomized trial of this nature will ever be performed. Without such data, however, some authors remain skeptical that surgical resection adds significant benefit.^4,5 Opponents to this approach point out that larger trials claiming improved survival after metastasectomy have been conducted in heterogeneous populations with tumors of mixed histologic types and mixed doubling times. The patients who benefit the most from surgical resection have a small tumor burden and a long doubling time (DFI), and this group may be able to live a long time with their disease even without surgical resection. The skeptics argue that a hypothetical study population that included slow-growing tumors in 40% of the subjects would produce a 30% 5-year survival after surgery, and that same 30% also would still be alive without an operation.

These arguments highlight the heterogeneity of this patient population and emphasize the need to tailor the surgical approach to each individual patient. Patients with dozens of metastases or rapid recurrence after a previous pulmonary metastasectomy will not gain major benefit from surgery. A very elderly patient with a slow-growing metastasis that would require pneumonectomy for resection might be better treated in other ways. These exceptions still leave many patients with pulmonary metastases that can be removed safely with an anticipated low morbidity and mortality.⁶

A large volume of retrospective data is available to substantiate a significant long-term survival with pulmonary metastasectomy. When these data are compared with those of patients with pulmonary metastases who did not undergo metastasectomy, it is likely that pulmonary metastasectomy affords a distinct survival benefit.^7–13 Furthermore, resection has other advantages. It can prevent further growth and consumption of lung tissue (dyspnea), hemoptysis, and chest wall invasion with subsequent pain.

The International Registry of Lung Metastases was established in 1991 to document long-term results and has accrued data on 5206 cases of pulmonary metastasectomy. The distribution of primary malignancies in this data bank was shown to be 43% carcinoma, 42% sarcoma, 7% germ cell tumors, and 6% melanoma. Actuarial 5- and 10-year survival rates after complete metastasectomy were 36% and 26%, respectively. Determinants of improved survival include complete resection, DFI (time from removal of primary tumor to recognition of pulmonary metastases) of 36 months or greater, and single metastasis. These results provide strong evidence that pulmonary metastasectomy is a safe and potentially curative procedure, because it is highly unlikely that a slow tumor doubling time could produce a 26% 10-year survival rate.⁶

Surgical resection of a single pulmonary metastasis has become a widely accepted treatment modality for properly selected patients. Opinions vary widely, however, regarding the utility of surgical resection in the face of multiple metastases, lung and lymph node metastases, or repeat metastases after a previous pulmonary metastasectomy. Each of these topics is explored in this chapter. We also examine the current indications for pulmonary metastasectomy, outcomes of surgery, prognostic indicators by cell type where data are available, and the approach to treatment of extrathoracic pulmonary metastases.

Ehrenhaft et al.¹⁴ published the first “criteria for pulmonary metastasectomy” in 1958. The current indications have remained largely the same but with slight evolution:

1. 
   

   Control of the primary site

   
   
2. 
   

   No other distant extrapulmonary metastatic disease or, if present, immediate plans to control it with surgery or another treatment modality

   
   
3. 
   

   Pulmonary metastases that are thought to be completely resectable, even if located in both the lungs

   
   
4. 
   

   Adequate cardiopulmonary reserve of the patient

   
   
5. 
   

   A technically feasible operation

Additional criteria for pulmonary metastasectomy have been described and include no other effective treatment except resection, difficulty of differential diagnosis from lung cancer, and symptomatic pulmonary metastases.^15–17 Among patients who do not fulfill the preceding criteria, surgery should proceed only if it will provide ample palliation, such as in situations of bronchial obstruction or distal pulmonary suppuration. The criteria for surgical resection will continue to evolve as we gain a better understanding for cell type-specific tumor biology and as improved systemic treatment becomes available.

Once it is determined that a patient meets the criteria for surgical intervention, the decision to proceed should be made in cooperation with a thoracic surgeon and a medical oncologist. A multidisciplinary approach offers the benefit of coordinating the timing of surgery and systemic treatment both now and in the face of future recurrence.

Preoperative staging and operative planning largely depend on cross-sectional imaging. Radiologic staging is inaccurate in a large proportion of patients, however, and underestimates the burden of disease. In many centers, thorough intraoperative staging by open bimanual palpation is performed in every patient to optimize resection of all metastatic deposits, particularly when more than one lesion is identified on preoperative radiographs.⁶

Helical CT scanners are now widely available. They allow thin-section imaging of the chest and detect approximately 20% to 25% more nodules than conventional CT scanning.^18,19 Large retrospective studies comparing high-resolution helical CT scanning with intraoperative detection of lesions by manual palpation have demonstrated sensitivities of 78% to 82% for CT detection. Approximately 22% of patients would have residual malignant deposits detectable by palpation if CT alone was used to guide resection.^20,21 Helical CT scanning may not be sensitive enough to obviate the need for manual lung palpation if the goal is resection of all detectable metastases. The magnitude of survival benefit with removal of deposits so small that they can only be detected by palpation, however, is uncertain. This is an important issue with the availability of minimally invasive thoracoscopic approaches to pulmonary metastasectomy that preclude manual palpation of the lung.

Helical CT scanning is most likely to miss nodules smaller than 6 mm in diameter. Sensitivity of CT scanning decreases in proportion to the size of the metastatic lesion. Sensitivity is 100% for lesions larger than 10 mm but only 66% for lesions between 6 and 10 mm.²¹ Manual palpation can detect 2-mm nodules at the surface of the lung and 4-mm nodules in the central part of the lobe. Clearly, a CT scan can preclude surgery if the number of nodules prevents a feasible operation.

There is no pathognomonic radiographic feature that distinguishes metastatic disease from primary lung cancer. That said, metastatic nodules often are observed to be well-circumscribed spherical deposits with smooth margins. They are predominantly subpleural in location or located in the outer third of the lung fields, and when multiple nodules are present, the probability of metastatic disease increases significantly. So-called lollipop nodules, which have the appearance of distinct round nodules at the end of a terminal pulmonary artery branch, also raise suspicion for a metastatic process. Primary bronchogenic lung cancer, conversely, often demonstrates irregular borders and associated linear densities.

The presence of a new radiographic nodule in a patient with prior malignancy represents a cancer in more than two-thirds of cases, probably as a function of nodule size (Table 78-1). For patients with a history of extrathoracic malignancy, the probability of a malignant solitary pulmonary nodule ranges from 67% for subcentimeter nodules to 91% for nodules larger than 3 cm. For all lesions smaller than 3 cm, the chance is essentially equal that the nodule represents a primary lung cancer or extrathoracic metastasis. For nodules larger than 3 cm in size, the probability of a primary lung cancer is greater.²²

Many patient and tumor factors have been found to predict improved survival after metastasectomy. Most commonly, these include a long DFI after treatment of the primary tumor, a low number of pulmonary metastases, and favorable cell type.⁶ The actual determinants may be discordant among different reports, likely owing to variance in definitions, measured endpoints, different grouping of cell types, and perhaps different tumor biology.

One positive predictive element ubiquitous to nearly all reports of pulmonary metastasectomy is the poor consequences of incomplete resection. Complete removal of all metastatic deposits is associated with long-term survival (Fig. 78-1).

DFI is regarded by many authors to be important. However, in a review of 32 retrospective reports of pulmonary metastasectomy, 19 reports determined that DFI was a significant prognostic factor, whereas 13 indicated that it was of no consequence.²³ The heterogeneous and small populations represented in these studies make this point difficult to interpret. The International Registry of Lung Metastases was established in 1991 to answer these types of questions. This registry, reported over 20 years ago, has accumulated its data through voluntary reporting by surgeons throughout the world. DFI is an important prognostic marker in this registry. It is important to note that the DFI is considered in terms of likelihood of achieving long-term disease-free survival but is not an absolute indication or contraindication to surgery.

Studies are evenly divided with respect to whether the number of metastatic lesions affects prognosis after pulmonary metastasectomy. Based on 15 reports in the literature, Todd²³ found that the number of metastatic lesions was a consistent factor for sarcomatous metastases, in which fewer than five lesions was associated with a more favorable outcome.²³ For epithelial tumors, the probability of incomplete resection has been a function of the number of pulmonary nodules (Fig. 78-2)²⁴ and the presence of more than one lesion may increase the probability of lung metastases to recur.²⁵ The important issue for the surgeon considering resection of multiple metastases is the feasibility of the operation. If several nodules need to be removed from the same lobe or a central nodule needs to be removed, a lobectomy may be required. As more lung tissue is removed, the perioperative risks increase.

Histology of the tumor itself is remarkable for the extremes of survival benefit. Germ cell tumors are associated with a very good prognosis. The prognosis associated with multiple melanoma metastases, lung primary metastases to the other lung, and pancreatic metastases is so poor that surgery likely will not benefit the patient.²⁶

Two main principles direct the surgical approach for resection of pulmonary metastases: complete resection of malignancy and maximal sparing of normal lung tissue. Complete resection of metastatic disease is not only the goal but also an important predictor of survival in nearly all reported series. All resections are performed conservatively, leaving as much normal parenchyma as possible. For peripheral nodules, this usually means wedge resection. For deeper nodules, segmentectomy may be required. This conservative approach leaves the patient with a greater degree of cardiopulmonary reserve to withstand subsequent treatments, should a recurrence appear, and maintains the patient’s quality of life. Mortality rates of pulmonary metastasectomy do not differ from those of resection for lung cancer and range between 0.6% and 2%.^6,27

Bronchoscopy is indicated in patients with centrally located lesions, in patients with symptoms of airway involvement, and in patients with cell types that are prone to endobronchial involvement, such as breast, colon, and renal cell cancers.²⁸

Single-lung anesthesia is used. Complete atelectasis of the lung will ensure adequate palpation of pulmonary parenchyma in open procedures and permits the technique of thoracoscopic exploration and resection.

The choice of incision for unilateral disease is somewhat controversial. Lateral thoracotomy has been the most commonly described approach to pulmonary metastasectomy. This approach offers adequate access to all areas of the hemithorax and permits wedge or anatomic resection under direct vision.

Some authors favor median sternotomy as an approach to unilateral disease. This incision has the advantages of simultaneous examination of both the lungs, identification and treatment of contralateral occult disease, and reduced postoperative discomfort and deficit in pulmonary function. Its disadvantage in pulmonary metastasectomy is difficult exposure of the posterior costovertebral lung fields and the lateral left lower lobe. The bilateral anterior thoracotomy (clamshell incision) provides excellent exposure to the posterior aspect of both lungs, but is complicated by increased postoperative pain.

Inspection of both hemithoraces in treatment of unilateral disease will identify occult tumor deposits in some cases; however, there does not appear to be a survival advantage to this approach compared with lateral thoracotomy.²⁹ Known bilateral lesions are resected via median sternotomy, the clamshell approach, or two-stage bilateral thoracotomy.

Metastatic lesions involving the diaphragm, chest wall, mediastinum, and pericardium are often resectable. Five-year survival after extended resections including chest wall and diaphragm has been reported to be as high as 25%.³⁰