Resection of Pulmonary Metastases: a Mechanical Solution for a Biological Problem

Isolated pulmonary metastases (PM) represent a unique manifestation of the myriad presentations of systemic spread from a primary neoplasm. Selected patients with metastases isolated within an organ system that has significant reserve (such as the lung for metastases of various solid tumors, the liver for colorectal metastasis, local and regional nodal metastasis of melanoma, etc) can have these metastases resected safely with a number of different surgical techniques, all of which provide complete resection and negative margins and leave sufficient residual functional tissue.

Resection for PM has been described since 1884.[1] These early descriptions are even more remarkable considering the state of analgesia, anesthesia, and the fact that positive pressure ventilation had not yet been described! One early successful resection of a solitary metastasis from renal cell carcinoma in 1939 provided a 23-year post-thoracotomy survival.[2] The role of resection for patients with PM from osteogenic and soft-tissue sarcoma was examined in the early 1980s in patients with primary sarcomas treated within the Surgery Branch of the National Institutes of Health[3,4] and elsewhere,[5] confirming the advantages of complete resection and identifying prognostic characteristics. Does resection improve survival? Or is resection simply associated with long-term survival? Appropriately powered randomized clinical trials testing therapeutic approaches for patients with PM are needed. Until data from such trials are available, the best clinical evidence comes from collected series of patients or registries.[6]

In their review, Kon and Martin describe appropriately the criteria for treatment of PM with a focus on the roles of patient selection, complete resection, and multidisciplinary care. In addition to the selection criteria for resection that are set forth in the paper, I would include additional criteria for complete or partial resection-such as providing a diagnosis; evaluating the effects of chemotherapy with resection of residual disease; and obtaining tumor for markers, immunohistochemical studies, vaccine, etc. Although rare and requiring that patients be highly selected, resection of large intrathoracic tumors can palliate symptoms and decrease tumor burden. A large solitary metastasis may cause a “tumor-thorax,” with shift of the mediastinum and compression of the heart, which can impair cardiac preload. Resection may require decompression of the heart with cardiopulmonary bypass to provide support during resection of the mass.

Resection or other local control strategies will depend on the surgeon and his or her experience, as well as on the patient’s condition and the number/location of metastases. Any surgical strategy should contribute to the goal of complete resection of the metastases with minimal morbidity. I favor complete resection of all metastases in a single operation, or in bilateral staged mini-thoracotomies. Meticulous palpation of lungs, identification of nodules, and complete resection make for the most consistent long-term outcome involving a single episode of care. Limited resection with thoracoscopy can allow residual nodules, granulomas, scar, or intraparenchymal lymph nodes to remain. These parenchymal abnormalities may be identified early in the postoperative period and mistaken for metastases on subsequent films. Complete resection will also identify additional pathologies. In one recent patient, I removed several nodules from the lung that included a PM from sarcoma; granulomatous disease from histoplasmosis; and a small, unsuspected non–small-cell lung cancer. All margins were negative.

In general, thoracoscopy or VATS (video-assisted thoracic surgery) is appropriate for isolated peripheral lesions of nonsarcomatous pathology. Given the high incidence of occult metastasis from sarcoma identified during manual palpation of lung, thoracoscopy may be just an initial step on the journey toward a sarcoma patient’s complete surgical care. A mini-thoracotomy through a vertical axillary incision can be easily created to facilitate manual palpation along with resection of all lung nodules. Patients with multiple PM, or more centrally located metastases, may be best served by a direct or open approach. Paradoxically, this open approach may provide more normal tissue sparing in that discrete, isolated disease can be identified and the sequence of resections planned to minimize the amount of normal tissue removed while still achieving negative margins. The use of the thoracic epidural is ubiquitous in my practice and provides excellent analgesia, rapid ambulation, and early discharge. Other local control strategies, such as cryotherapy, radiofrequency ablation, or stereotactic body radiation therapy (SBRT), have been reported in small numbers of patients.

Patients with soft-tissue sarcomas may have a 5-year survival of approximately 25% to 30%. Despite complete resection, disease will recur in 70% of patients. Of those whose disease recurs, 25% to 30% may achieve 5-year survival following re-resection. The concept of re-resection for isolated PM is valid. A short disease-free interval correlates with a more aggressive tumor and suggests consideration of chemotherapy or other systemic therapies following resection. However, given the recurrence rate following resection of PM, additional strategies are necessary.

The value of chemotherapy for treatment of multiple and resectable PM is unclear, although systemic chemotherapy is routinely considered for (unresectable) metastatic disease. Induction therapy for primary non–small-cell lung cancer can be given safely[7] and can have a significant biological effect.[8] Most studies of induction chemotherapy for lung metastases have small numbers of patients and are under-powered. Nonetheless, I am a proponent of consideration of induction chemotherapy, particularly for multiple PM from soft-tissue sarcoma. Induction chemotherapy followed by resection may be predictive, providing a biological “stress test” that can identify the effectiveness of the chemotherapeutic agents used. Two cycles of chemotherapy are typically given, and an assessment of response measured. If a response has been noted, additional chemotherapy is given until the response has stabilized. At that point the patient would be reevaluated for resection.

Isolated lung perfusion (ILP) theoretically has a significant advantage in that it delivers large concentrations of chemotherapy to the lung and minimizes systemic toxicity. However, the strategy has significant limitations. ILP is a one-time event-and a complex operation requiring use of a separate lung infusion circuit for the infusate. During ILP, lung ischemia and endothelial injury must be minimized and chemotherapy concentrations optimized for the tumor. The concentration of the chemotherapeutic agent and the circulation time during ILP must be sufficient to allow effective exposure of the chemotherapeutic agent to the PM. Exposure of chemotherapeutic agents to metastases with a significant fibrous stroma (as in some soft-tissue sarcomas) or with calcification (as in osteogenic sarcoma) would be limited or not feasible. Improved strategies for achieving better exposure to effective drugs, as well as improved percutaneous catheter techniques, are needed.

Financial Disclosure:The author has no significant financial interest or other relationship with the manufacturers of any products or providers of any service mentioned in this article.

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REFERENCES

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2. Barney JD, Churchill EJ. Adenocarcinoma of the kidney with metastasis to the lung cured by nephrectomy and lobectomy. J Urol. 1939;42:269-76.

3. Putnam JB Jr, Roth JA, Wesley MN, et al. Analysis of prognostic factors in patients undergoing resection of pulmonary metastases from soft tissue sarcomas. J Thorac Cardiovasc Surg. 1984;87:260-7.

4. Putnam JB Jr, Roth JA, Wesley MN, et al. Survival following aggressive resection of pulmonary metastases from osteogenic sarcoma: analysis of prognostic factors. Ann Thorac Surg. 1983;38:516-23.

5. Martini N, Bains MS, Huvos AG, Beattie EJ, Jr. Surgical treatment of metastatic sarcoma to the lung. Surg Clin North Am. 1974;54:841-8.

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7. Pisters KM, Vallieres E, Crowley JJ, et al. Surgery with or without preoperative paclitaxel and carboplatin in early-stage non-small-cell lung cancer: Southwest Oncology Group Trial S9900, an intergroup, randomized, phase III trial. J Clin Oncol. 2010;28:1843-9.

8. Albain KS, Swann RS, Rusch VW, et al. Radiotherapy plus chemotherapy with or without surgical resection for stage III non-small-cell lung cancer: a phase III randomised controlled trial. Lancet. 2009;374:379-86.