Surgical Principles and Approaches
Many options exist for the resection of pulmonary metastases. Unilateral disease can be approached via a thoracotomy or video-assisted thoracoscopic surgery (VATS); bilateral disease can be approached via a clamshell incision, median sternotomy, or sequential thoracotomies (Figure 4).
The advantage of open resection includes excellent visualization, greater ability to preserve lung parenchyma, and perhaps most importantly, the ability to palpate for nodules. Parsons and others have shown that in up to 46% of patients, preoperative CT scans failed to predict the number of nodules found at thoracotomy.This was also seen by the University of Alabama group, who found that 1 in 5 patients had ipsilateral non-imaged malignant metastases found at thoracotomy. In the most elegant study to date evaluating the importance of open lung palpation, a prospective trial from Memorial Sloan-Kettering Cancer Center, patients were preoperatively evaluated with a CT scan and subsequently underwent VATS pulmonary metastasectomy, but they then were immediately converted to a thoracotomy to evaluate for missed nodules. The investigators found that 10 of the first 18 patients had lesions missed by CT scan and VATS alone. Because of the dramatic results, the study was closed early.
Despite these findings, VATS still offers perceived advantages over open techniques, with less pain and shorter hospital stays. In lung cancer patients, compliance with adjuvant therapy regimens is greatly improved, and this may be relevant in sarcoma patients as well. Reoperation after VATS is considered less morbid and generally “easier” on patient and surgeon, again a relevant concern given the frequency of new metastases years after initial resection. For all these reasons, VATS is appealing to both patients and surgeons. Proponents of open metastasectomy argue that missed nodules will guarantee the need for reoperation in the future, yet there is no evidence to support the contention that the lesions missed by VATS (generally < 5 mm) are of any substantial clinical significance. In several studies, survival outcomes do not seem to be negatively impacted by the use of VATS for metastasectomy.[24,25] Perhaps a compromise exists between these two opposing viewpoints: use of a subxiphoid port that can allow the benefits of VATS with the possibility of manual lung palpation.[26,27]
We generally reserve thoracoscopy for patients with solitary, peripheral lesions that are large enough to localize with instrument palpation. Patients are counseled extensively about the risk of missed additional lesions with a VATS approach compared to thoracotomy. Careful postoperative surveillance is recommended in either case to check for local recurrence, new lesions, or missed lesions that have enlarged.
Although bilateral metastases can be approach via either sequential VATS or thoracotomies, they often require a recovery period of 4 to 8 weeks between operations. Median sternotomy and clamshell incisions have the advantage of a single trip to the operating room. The benefit of a median sternotomy incision over bilateral thoracotomy or a clamshell incision is less postoperative pain and perhaps fewer postoperative pulmonary complications. Unfortunately, with sternotomy, exposure of posterior or hilar lesions and left lower lung fields is often suboptimal. In comparison, a clamshell incision offers excellent access to all lung fields, but it results in significant postoperative pain and functional impairment. Additionally, a clamshell incision requires the sacrifice of both internal mammary arteries. It is important to know the advantages and shortcomings of each incision in order to individualize recommendations to patients.
Mediastinal lymph node dissection
Pulmonary metastases from carcinomas are occasionally accompanied by, or perhaps lead to, mediastinal lymph node metastases. While consideration of this possibility can be clinically important in carcinomas, it is rarely seen with sarcoma.[28,29] Therefore, lymphadenectomy is not routinely recommended during resection of pulmonary metastases from sarcoma.
Five-year survival for both soft-tissue and osteogenic sarcoma after complete resection of lung metastases ranges from 21% to 38%.[11-13,16] Pastorino et al found that approximately 60% of patients had recurrent metastatic disease, and about two-thirds of these recurrences were intrathoracic. More than 50% of patients underwent a second metastasectomy, with 44% surviving 5 additional years. Similar results were reported by Briccoli and et al, who showed a 5-year survival of 32% from repeat metastasectomy. Given these outcomes with repeat resection, it is logical that close radiologic follow-up is useful to identify new lung nodules before they become inoperable. NCCN guidelines suggest chest CT or plain chest radiography every 3 to 6 months for 2 to 3 years, then every 6 months for 2 years, then annually.
Other Treatment Modalities
Several new alternatives and adjuncts to surgery have been proposed, including stereotactic radiosurgery, radiofrequency ablation (RFA), and isolated lung chemotherapeutic perfusion. Stereotactic radiosurgery has previously been used for patients with inoperable primary lung tumors. A study evaluating its use in 35 patients with pulmonary metastases showed that 77% were alive at a median of 18 months. At this time, it is not considered a substitute for surgery, but rather an alternative when patients are unfit for surgery or have had multiple reoperations and do not have adequate lung function for further surgery. RFA has also been used in situations in which surgery was felt to be too great a risk. One report evaluated 47 metastases in 29 nonsurgical patients. It reported 1- and 3-year survival rates of 92% and 65%. Despite these promising early results, there are significant limitations to RFA. Centrally located nodules are not generally amenable to RFA, especially when lesions are in close proximity to large vessels. Additionally, because margins are not attainable and there is usually a residual mass (scar tissue, necrotic tumor, or perhaps residual tumor), it is difficult to determine whether local control has been achieved.
Isolated lung perfusion utilizes chemotherapeutic agents infused directly into the pulmonary vascular bed, allowing local drug levels that would be toxic systemically. Promising results have previously been seen in animal studies. A phase I clinical trial in humans illustrated the safety and feasibility of this approach and its potential to at least stabilize disease. Multiple drugs alone or in combination can be used with this modality, including doxorubicin(Drug information on doxorubicin), cisplatin, tumor necrosis factor alpha, interferon gamma(Drug information on interferon gamma), and melphalan(Drug information on melphalan). Pending phase II trials will help determine whether this modality has a role in the treatment of sarcomatous pulmonary metastases.
While there is a lack of phase III studies comparing pulmonary metastasectomy to other options in metastatic sarcoma, substantial retrospective data support a survival advantage for aggressive resection in these patients. Careful preoperative assessment both physiologically and oncologically is key to identifying those patients most likely to benefit from resection of sarcomatous lung metastases. Controversy persists regarding the optimal surgical approach; however, VATS is frequently preferred by patients and surgeons and is probably acceptable in cases with a low number of nodules that are periphally located. For medically inoperable patients, RFA or stereotactic radiosurgery provide some degree of local control and represent a reasonable alternative to surgery. The use of chemotherapy remains unproven in terms of survival benefit; optimal timing in relation to metastasectomy is also unknown. Review of complex cases in a multidisciplinary setting is highly recommended.
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.