Minimally invasive metastasectomy for skin and soft tissue malignancies: sarcomas, melanoma, and breast cancer: a narrative review
Review Article

Minimally invasive metastasectomy for skin and soft tissue malignancies: sarcomas, melanoma, and breast cancer: a narrative review

Benjamin A. Palleiko ORCID logo, Mark W. Maxfield ORCID logo

Division of Thoracic Surgery, Department of Surgery, UMass Chan Medical School, Worcester, MA, USA

Contributions: (I) Conception and design: Both authors; (II) Administrative support: None; (III) Provision of study materials or patients: None; (IV) Collection and assembly of data: Both authors; (V) Data analysis and interpretation: Both authors; (VI) Manuscript writing: Both authors; (VII) Final approval of manuscript: Both authors.

Correspondence to: Benjamin A. Palleiko, BS. Division of Thoracic Surgery, Department of Surgery, UMass Chan Medical School, 67 Belmont Street, Worcester, MA 01605, USA. Email: Benjamin.Palleiko@umassmed.edu.

Background and Objective: Pulmonary metastasectomy (PM) is a thoracic surgery operation in which metastatic disease is surgically resected from the lung. Traditionally, PM has been performed via thoracotomy, to allow surgeons to manually palpate the lung and detect additional disease not detected on preoperative imaging. However, the contemporary widespread use of minimally invasive thoracic surgery raises additional questions about the suitability of a minimally invasive approach. In this narrative review, we cover the relevant considerations of minimally invasive PM for soft tissue sarcoma, breast cancer, and melanoma.

Methods: A literature review was conducted using the PubMed/MEDLINE database including all relevant articles through March 2023. Articles were reviewed for relevance by the authors. There were no restrictions on type of study included.

Key Content and Findings: Preoperative, intraoperative, and postoperative considerations for a minimally invasive approach to PM for soft tissue sarcoma, breast cancer, and melanoma are summarized in this review. Wedge resection was the most common type of resection for all three malignancies. The role of lymph node dissection or sampling remains controversial and underreported in the literature. No studies were identified that demonstrated inferior overall survival or disease-free survival with minimally invasive PM for these malignancies.

Conclusions: For soft tissue sarcoma, breast cancer, and melanoma, a minimally invasive approach to PM is likely appropriate for select patients. Studies focusing on PM in the setting of breast cancer and melanoma are particularly limited and additional reports would be of great benefit to the literature.

Keywords: Sarcoma; breast cancer; melanoma; metastasectomy; minimally invasive thoracic surgery


Received: 31 May 2023; Accepted: 02 August 2023; Published online: 23 August 2023.

doi: 10.21037/vats-23-46


Introduction

Background

Pulmonary metastasectomy (PM) is the surgical removal of metastatic disease from the lung. The lungs are a frequent site of metastasis for many different cancers, in part due to their large surface area and blood supply (1). These cancers include, but are not limited to, colorectal cancer, renal cell carcinoma, sarcoma (both soft tissue and osteosarcoma), breast cancer, melanoma, and various head and neck malignancies (2). Patients who are to undergo PM should be carefully selected. There are four generally agreed upon criteria for any patient to undergo PM; these are as follows: (I) the patient is a suitable surgical candidate with appropriate surgical risk. (II) The primary tumor is either controlled or controllable. (III) There are no extrathoracic metastases, and if there are, they should be controllable with either surgery, or another effective treatment such as radiation. (IV) Complete resection of pulmonary metastases is thought to be possible (1,2).

Rationale and knowledge gap

If patients fulfill these criteria and are selected to undergo PM, there are disease-specific factors that should be considered. However, there are few studies that examine the role of PM for these malignancies. Additionally, much of the literature on PM for these malignancies focuses on a traditional approach via thoracotomy. There is limited data regarding a minimally invasive approach, which is particularly relevant in the contemporary era of minimally invasive thoracic surgery.

Objective

In this narrative review, we cover the important preoperative, intraoperative, and postoperative considerations of PM in the setting of soft tissue sarcoma, breast cancer, and melanoma. When possible, we attempt to highlight topics relevant to a minimally invasive approach to PM for these malignancies. We present this article in accordance with the Narrative Review reporting checklist (available at https://vats.amegroups.com/article/view/10.21037/vats-23-46/rc).


Methods

A literature review was conducted using the PubMed/MEDLINE database in March 2023. Various search terms were used, such as “minimally invasive metastasectomy”, “pulmonary metastasectomy”, or “VATS”, along with the Boolean operator AND, followed by “sarcoma”, “breast cancer”, or “melanoma”. Articles were reviewed for relevance by the authors (BAP and MWM). All relevant articles published either in English or articles with a full English translation available were included. There were no date restrictions, nor were there restrictions on type of study included (Table 1).

Table 1

Review methodology

Items Specification
Date of search March 1st 2023
Databases and other sources searched PubMed/MEDLINE
Search terms used Combinations of relevant search terms such including: “minimally invasive metastasectomy”, “pulmonary metastasectomy”, “VATS”, “sarcoma”, “breast cancer”, “melanoma”. Reference lists of articles were manually reviewed for articles not identified in initial search
Timeframe No date restriction
Inclusion and exclusion criteria Inclusion criteria: English. Studies reporting on minimally invasive approaches to pulmonary metastasectomy
Exclusion criteria: No full English translation available
Selection process Articles reviewed and selected by B.A.P. and M.W.M.

VATS, video-assisted thoracic surgery.


Soft tissue sarcomas

Background

Sarcomas are tumors derived from embryonic mesoderm and are known to frequently metastasize to the lungs (3). PM for soft tissue sarcoma is common, accounting for 751 out of 5,206 cases (14.4%) in the International Registry of Lung Metastasis (2,4). When considering soft-tissue sarcomas, rates of pulmonary metastasis may be as high as 40% (5). A systematic review including 1,004 patients who underwent PM for soft tissue sarcoma identified leiomyosarcoma, malignant fibrous histiocytoma and synovial sarcoma as the most commonly resected subtypes (6). Multiple studies have demonstrated improved survival in patients who undergo PM for soft tissue sarcoma compared to nonsurgical management (7-9). According to the National Comprehensive Cancer Network (NCCN) clinical practice guidelines for soft tissue sarcoma, resection for metastatic disease should be considered if the primary tumor is able to be controlled (10).

Preoperative considerations

It is important to identify patients who will benefit from PM for soft tissue sarcoma. In addition to the four main criteria generally agreed upon for metastasectomy (2), there have been several prognostic factors identified specific to soft tissue sarcomas. A longer disease-free interval (DFI) prior to surgery has been associated with prolonged survival with many studies reporting increased survival with a DFI of at least 1 year (11-15). Several studies exist that demonstrate a larger number of resected nodules portends a worse prognosis, with Casson et al. observing improved survival in patients with fewer than 3 nodules resected and Putnam et al. observing improved survival in patients with fewer than 4 nodules resected (14,16,17). However, even in patients with a large number of nodules resected, the ability to completely resect the nodules is still a better predictor of survival (18). The presence of bilateral metastases has not been demonstrated to have any effect on survival (14). Patients with leiomyosarcoma may benefit more from PM compared with other subtypes of soft tissue sarcoma (14).

Intraoperative considerations

Open versus minimally invasive approach

Regarding operative approach, patients may be good candidates for minimally invasive resection if they have few metastases, smaller lesions (<30 mm), peripheral lesions, and a longer DFI (19-21). Studies directly comparing minimally invasive and open approaches for PM in soft tissue sarcoma patients are limited. In a nearly 23-year retrospective review of 539 patients who underwent PM for soft tissue sarcoma, 156 (29%) underwent minimally invasive resection (11). Unsurprisingly, the percentage of minimally invasive resections drastically increased over the course of the study period. There were no differences observed in rate of R0 resection or risk of recurrence between minimally invasive and open approaches. Interestingly, in a multivariable analysis of overall survival, minimally invasive resection was associated with a decreased risk of death compared to an open approach (11). Lin et al. also observed increased overall survival with a minimally invasive approach (22). However, in both studies, the observed increase in overall survival was partially attributed to patient selection bias (11,22).

There are other retrospective studies that have not observed any survival benefit of minimally invasive PM for soft tissue sarcoma. Reza et al. detailed 118 patients over 13 years who underwent complete R0 resection (23). Of these 118 patients, 44 (37.3%) underwent PM via a video-assisted thoracic surgery (VATS) approach with no observed difference in overall survival compared with an open approach (23). In a similar retrospective review of 48 patients by Predina and colleagues, 13 (27.1%) underwent a VATS procedure. Again, there were no differences observed in overall survival or disease-free survival (24). Notably, none of the aforementioned studies were designed to specifically compare VATS and minimally invasive approaches and this is a topic that warrants further investigation. However, from the body of evidence available, it does seem that a minimally invasive approach is appropriate when complete resection is feasible as no studies demonstrated inferior outcomes with a minimally invasive approach.

Metastatic lung lesions for soft tissue sarcoma are often small. Though computed tomography (CT) imaging has improved significantly with cuts as small as 1 mm used regularly, up to 37% of patients still have lesions discovered during surgery that were not noted on imaging (25). Therefore, manual lung palpation with an open approach has been historically preferred to assist in detection and resection of unknown metastatic disease (21,26,27). Given the concern regarding the inability to palpate the lung with minimally invasive approaches, there have been techniques described to help discover occult metastatic disease. Reza et al. in their 13-year series of PM for sarcoma developed a modified VATS technique where nearly all lung parenchyma could be brought into contact with the surgeon’s finger through one of the VATS port incisions, allowing for detection of lesions as small as 1 mm. Using this technique, they did not observe any difference in mean number of lesions detected or mean number of lesions <1 cm that were resected when comparing VATS and open approaches (23).

More recently, intraoperative molecular imaging has been demonstrated to be a promising approach for detection of occult pulmonary lesions from sarcoma. In this technique, near infrared tracers are injected into the patient which then target occult pulmonary metastases. The occult metastatic lesions can then be visualized intraoperatively using near infrared cameras, with a high rate of success (28). Though further investigation is needed, the use of near infrared technology for detection of occult pulmonary malignancy is a natural fit with minimally invasive surgery, during which near infrared imaging is already routinely used.

Extent of pulmonary resection

The extent of pulmonary resection should be a balance between chance of achieving R0 resection while at the same time preserving as much lung function as possible. Many studies report high prevalence of wedge resection for pulmonary sarcoma metastases, which makes sense given that many sarcoma metastases occur in the lung periphery (3,11,19,29-31). For large or centrally located metastases, more extensive lung resection (segmentectomy, lobectomy, or pneumonectomy) may be required (30,32). A consensus has not been agreed upon regarding adequate margins for sarcoma-related PM (30). However, a surgical margin to nodule size ratio of greater than or equal to 1 has been shown to be associated with increased disease-free and overall survival (33). Therefore, similar to primary lung malignancy, if possible, a margin of at least 10–20 mm should be taken (34).

Role of lymph node sampling and dissection

Lymph node metastasis of sarcomas are rare. In a 10-year review of a prospective sarcoma database only 2.6% of sarcomas were found to have lymph node metastases (35). This is consistent with findings from the International Registry of Lung Metastases, which also reported a 2% rate of mediastinal or hilar lymph node involvement (4). Gafencu et al. recently published a 20-year single-center retrospective study of 327 patients who underwent PM for sarcoma. In this cohort, 122 patients underwent lymphadenectomy, of which only 6 had positive lymph nodes (4.9%). Lymph node involvement did not impact survival (29). In a smaller study of 139 patients who underwent PM, only one out of 17 metastasectomies for sarcoma (5.9%) had positive lymph node involvement (32). Given the low occurrence of lymph node involvement with sarcomas, and that even with lymph node involvement clinical management is unlikely to be altered, the value of lymphadenectomy for sarcomas is limited and not routinely recommended (3,21).

Postoperative considerations

According to the NCNN guidelines, patients should undergo follow-up imaging every 3–6 months for 2–3 years, every 6 months for the subsequent 2 years, and then annually (10). Many patients with sarcoma metastases to the lungs will require repeat operation, which may be facilitated by a minimally invasive approach (21). In a Kim et al. study, 33% of patients who underwent metastasectomy for sarcoma required reoperation (19). Notably, there is still a survival benefit for patients who undergo repeat metastasectomy for sarcoma, as 30–40% of patients who require reoperation will survive an additional 5 years (3,36).

Summary

A minimally invasive approach to PM for soft tissue sarcoma is reasonable for patients with small tumors that are peripherally located. There does not appear to be a significant difference in overall survival or disease-free survival rates between minimally invasive and open PM for soft tissue sarcoma. Though minimally invasive approaches historically have not allowed for manual palpation of the lung to detect small metastases not visualized on preoperative imaging, techniques have been described that may alleviate this limitation. Additionally, a minimally invasive approach may allow for easier future reoperation, which is frequently required for sarcoma metastases. When considering extent of resection, wedge resection is reasonable for most patients, given that R0 resection is feasible. For patients with larger or centrally located disease, more extensive lung resection may be required. Patients who undergo PM for sarcoma require close radiologic follow-up to quickly detect subsequent metastatic disease.


Breast cancer

Background

Breast cancer is the most commonly diagnosed cancer in the United States and accounts for almost one third of all cancer diagnoses in women (37). Approximately 5–10% of cases involve distant metastases at time of diagnosis and 30% of patients experience recurrence (38). In a large, retrospective study of over 1,000 patients with metastatic breast cancer, 17.7% of cases involved the lung (39). In the International Registry of Lung Metastasis, breast cancer accounted for 396 out of 5,206 (7.6%) of cases (2,4). Prior to the advent of endobronchial ultrasound (EBUS) guided biopsy and CT guided biopsy, PM for breast cancer had a dual purpose of being both diagnostic and therapeutic (40). However, with the current widespread availability of these techniques for diagnosis, the purpose of PM for breast cancer has shifted towards a therapeutic intent (40).

Preoperative considerations

The standard of care for treatment of metastatic breast cancer is systemic therapy (38,41). However, in select patients with a limited number of metastatic lung lesions, there may be a role for metastasectomy (38,42). One of the most important preoperative considerations in patients with a lung nodule in the setting of prior breast cancer is to determine whether the nodule represents a metastasis or a primary lung tumor. In patients with breast cancer and a newly discovered lung nodule, it can be difficult to distinguish between the two based on imaging characteristics alone, and therefore tissue diagnosis via biopsy should be obtained prior to surgery (42).

Several prognostic factors have been identified for patient survival following PM for breast cancer. Most patients included in studies examining PM for breast cancer had fewer than 4 pulmonary metastases. Consistently, there was better overall survival observed in patients with fewer than 4 metastases, compared with 4 or more (43). A meta-analysis including 1,937 patients identified several positive prognostic factors for patients with breast cancer undergoing PM that included a DFI greater than 3 years, complete resection of metastases, presence of a single pulmonary metastasis, and hormone receptor positive disease (44). In this study, the 5-year overall survival rate was 46% (44). In comparison, a case series of patients with breast cancer metastases limited to the lung managed with chemotherapy alone observed a survival rate of 16% (45). However, this large difference in survival rates may be confounded by criteria for surgical eligibility, such as a high functional status. In a large, multi-institution retrospective analysis of 253 patients who underwent PM for breast cancer, again, DFI greater than 3 years and complete resection were also identified as positive prognostic factors. Larger tumor size was found to correspond with worse survival (46). However, this may reflect increased difficulty of complete resection with larger tumor size.

Intraoperative considerations

Open versus minimally invasive approach

Very few studies exist that report specifically on minimally invasive PM for breast cancer and no studies exist that directly compare an open versus minimally invasive approach. In studies that compare minimally invasive and open approaches for PM with mixed tumor types, representation of breast cancer patients is too small to draw any meaningful conclusions. This is a significant gap in the literature.

In a Chen et al. study of 41 patients who underwent PM for breast cancer, 14 patients underwent resection via a VATS approach. There was no significant difference in a univariate analysis of 5-year overall survival compared with the patients in their study who underwent resection via thoracotomy (47). In an analysis of breast cancer patients from the International Registry of Lung Metastasis, only 4% (n=17) patients underwent resection via a thoracoscopic approach, and they did not observe any difference in survival with respect to operative approach (48). Of note, the data set used in this study included patients who underwent resection from 1960–1994, and since then, minimally invasive thoracic surgery has become much more widespread. In a 13-year case series of patients with a solitary lung nodule in the setting of breast cancer, Rena et al. performed VATS lung resection in 33/79 (41%) of cases (49). They suggested that VATS is an acceptable approach for tumors that are peripherally located. Outcomes and survival with respect to operative approach were not compared in this study. Similarly, in a Meimarakis et al. study examining PM in 81 breast cancer patients, the authors shared that for peripherally located nodules, thoracoscopy was used. However, specific outcomes from this group were not reported (50).

Extent of pulmonary resection

In an analysis of metastasectomy for breast cancer in the International Registry of Lung Metastases, wedge or segmental resections were performed for 73% of resections. Patients who underwent wedge resection had a 5-year survival rate of 40% and median survival rate of 42 months. Notably, there was no significant difference in 5-year survival rates or median survival observed between type of resection (48). Similar to PM for other malignancy, lobectomy or more extensive resection may be required if the tumor is not amenable to complete resection via wedge resection (38,51). There are no specific margin guidelines for breast cancer metastases. However, for other pulmonary metastases, a margin of 10–20 mm has been recommended with wedge resection (52).

Role of lymph node sampling and dissection

Thoracic lymph node involvement is common in patients with thoracic metastases of breast cancer, with rates as high as 39% (38,53). However, the role of mediastinal lymph node dissection and/or sampling during PM for breast cancer remains underreported in the literature. According to the Society of Thoracic Surgeons (STS) Expert Consensus Document on Pulmonary Metastasectomy, mediastinal lymph node metastases in the setting of pulmonary metastases from breast cancer may be associated with decreased survival (51). Importantly, these lymph node metastases are frequently overlooked with preoperative imaging. In a Seebacher et al. study, unexpected lymph node involvement was found in 35.5% of breast cancer patients who underwent PM (54). Notably, however, in a retrospective of 81 patients where lymph node involvement was associated on univariate analysis with worsened survival (median survival with lymph node involvement 32.1 months, no lymph node involvement 103.4 months, P=0.095), the performance of lymph node dissection itself was not associated with survival (50). Therefore, though mediastinal lymph node dissection and/or sampling likely does not alter survival, it may be worthwhile to perform in order to further define patient prognosis.

Postoperative considerations

Re-examination of tumor receptor status should be performed after resection via immunohistochemistry, since metastases may exhibit different tumor characteristics than the primary breast tumor (55). Patients require close imaging follow-up with CT scans with a suggested interval of every 6 months for the first 2 years, and then every year for at least 5 years (42,56). In the International Registry of Lung Metastasis, there were 19 patients (4.8%) who underwent initial complete resection of pulmonary breast cancer metastases and subsequently underwent a second resection for additional metastatic disease. In these patients, there was a 53% 5-year survival rate, suggesting that repeat PM may be effective in select patients (48).

Summary

Though the mainstay of treatment for stage IV breast cancer is systemic therapy, there may be a benefit to PM for patients with a small number of pulmonary metastases (<4) that are completely resectable in the setting of a longer DFI. Patients with hormone receptor positive tumors may experience more of a survival benefit following PM for breast cancer. The data surrounding minimally invasive PM for breast cancer is much less robust than other malignancies, but outcomes and survival appear to be similar. Wedge resection is appropriate, given that R0 resection is feasible. Lymph node dissection and/or sampling may not provide a survival benefit but can potentially offer additional data regarding prognosis and therefore should be considered for these patients. Postoperatively, patients require close radiologic follow-up and should continue to follow with a medical oncologist.


Melanoma

Background

Melanomas are tumors derived from melanocytes, the melanin-producing cells in the skin. Though melanomas account for only 4% of skin cancers, they are responsible for 75% of skin-cancer related deaths (57). Approximately 4% of melanomas are stage IV with distant metastases at the time of diagnosis, and as high as 40% of metastatic melanoma cases involve the lung parenchyma (58,59). In selected patients, there is a demonstrated survival benefit with PM (60). In the International Registry of Lung Metastasis, PM for melanoma comprised 282 of 5,206 cases (5.4%) (2,4). The role of surgical intervention for pulmonary metastases from melanoma is still evolving as treatments for metastatic melanoma continue to improve (59).

Preoperative considerations

Unfortunately, prognosis for patients with metastatic melanoma is quite poor, with 5-year survival rates of 3–6% and an estimated median survival of 7.5 months in the absence of surgical intervention (59,61,62). However, in selected patients who undergo successful PM, 5-year survival rates have been reported as high as 35.1% with a median survival of 18.3 months (59,63). Several prognostic factors have been associated with worse survival after PM including a shorter DFI, evidence of extrathoracic metastases, and larger number of pulmonary nodules (4,61,64,65). Patients who have not responded well to systemic therapy are also less likely to benefit from metastasectomy (66). There has been a significant survival benefit associated with utilizing positron emission tomography (PET) scan prior to metastasectomy to exclude additional metastatic disease compared with CT imaging, thus preoperative PET scan should be performed in these patients (67-69).

Pathologic findings may help in determining prognosis, as Petersen et al. observed worse survival in patients with a nodular histologic subtype of melanoma (61). Tumor doubling time has also been associated with survival rates. In a study by Ollila et al., melanomas with a tumor doubling time of greater than 60 days were associated with a 5-year survival of 20.7% and median survival of 29.2 months. However, in patients with a tumor doubling time of less than 60 days, the median survival was 16.0 months with a 5-year survival of 0%. Thus, they recommended that PM not be performed if the tumor doubling time cannot be increased to over 60 days with systemic therapy (70). Notably, this study was performed in the late 1990s, prior to the emergence of newer therapies such a cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and programmed cell death-1 (PD-1) checkpoint inhibitors. Therefore, reexamination of this association in the current treatment era may be of benefit.

In summary, patients with melanoma should be considered for PM if they have a longer DFI (>1 year), fewer than 3 completely resectable pulmonary nodules, no evidence of extra-thoracic metastases or lymph node involvement, a tumor doubling time of greater than 60 days, and favorable response to systemic therapy (60). Surgeons should work in close collaboration with medical oncologists to determine the role of neoadjuvant or adjuvant therapy.

Intraoperative considerations

Open versus minimally invasive approach

Similar to other pulmonary metastatic disease, the debate regarding efficacy of minimally invasive PM for melanoma is centered around the inability to detect occult malignancy via manual lung palpation. Andrews et al. suggested that thoracoscopic PM for melanoma may be acceptable given that the patients underwent high-resolution chest CT prior to surgery and that the patient had fewer than 3 small peripheral nodules (71). Unfortunately, with pulmonary metastatic melanoma, there are no studies directly comparing a minimally invasive and open approach for resection, and much of the conclusions regarding the results of a minimally invasive approach must be drawn from subsets of larger studies.

In a review of patients included in a large cancer database, Hanna et al. reported a high utilization of VATS for PM in melanoma patients. They did not observe any significant differences in rates of positive margins or need for repeat operation when comparing VATS and thoracotomy. Overall and disease-free survival between the two approaches was not reported (72). Leo et al. did not observe any impact of surgical approach on survival. However, this study only included 7 patients (2.1%) who underwent thoracoscopic resection, likely limiting the ability to detect any differences between the two approaches (65). Though specific outcomes were not reported between the two approaches, Petersen and colleagues no longer prefer an open approach in melanoma patients and utilize a VATS approach. In their approach, they first inspect the visceral and parietal pleura for any evidence of dissemination, and use either the surgeons’ finger through the anterior access port or a thoracoscopic Foerster clamp to palpate the lung (61). Studies do exist that directly compare outcomes of minimally invasive and open metastasectomy of various cancer types, but representation of melanoma patients is low and conclusions are difficult to make that are specific to this subset of patients (31,73-75). A study specifically examining outcomes of minimally invasive PM for melanoma in the current era of high-resolution imaging would be of great benefit to the literature.

Extent of pulmonary resection

Similar to PM for other malignancies, the extent of pulmonary resection should be decided by the ability to achieve R0 resection while preserving as much functional lung parenchyma as possible. For peripheral nodules, wedge resection is likely sufficient, while for larger or centrally located nodules, more extensive resection such as lobectomy may be necessary. In several large studies of PM for melanoma, wedge resection was the most commonly performed procedure. Petersen et al. reported a 66% rate of wedge resection and Hanna et al. reported a similar rate of 64.6%. Lobectomy was the next most commonly performed operation performed in both studies with 30% (Petersen et al.) and 23.2% (Hanna et al.) of patients undergoing lobectomy (61,72).

Role of lymph node sampling and dissection

Patients that are selected to undergo PM for melanoma usually do not have any preoperative evidence of thoracic lymph node involvement (68). Therefore, the role of thoracic lymph node sampling or dissection for patients with metastatic melanoma is not well documented in the literature. Harpole et al. analyzed 945 patients with pulmonary metastatic melanoma and observed worse survival in patients with positive lymph nodes. However, in their analysis, they compared all patients with positive lymph node involvement to all patients without, regardless of whether the patients underwent PM (64). Thus, it does not address the question of whether or nodal involvement is a useful prognostic factor for surgical patients. Studies that directly address this question are limited and contradictory.

In a subset analysis of patients with surgically resected pulmonary melanoma metastases in the International Registry of Lung Metastases, nodal involvement did not impact overall survival (65). However, in a separate study of melanoma patients undergoing PM, Chua et al. observed a trend-level difference in survival, with patients who had no nodal involvement surviving a median of 27 months after surgical resection versus 16 months in those who did have positive nodes (P=0.074) (68). From their experience, the approach followed by Chua et al. is to perform lymph node sampling with intraoperative frozen section analysis on patients with noted bulky lymph nodes (either intraoperatively or preoperative imaging), and if positive, perform a complete lymph node dissection (68). Other surgeons prefer to be more aggressive with lymph node sampling, with an approach similar to lung resections for primary lung cancer; the rationale being that incidental discovery of lymph node involvement has been shown to portend worse survival in colorectal cancer and renal cell cancer (67). No approach has been demonstrated to be superior in terms of survival, and future studies should work to better describe their experience with lymph node sampling and dissection in patients undergoing PM for metastatic melanoma.

Postoperative considerations

Disease recurrence rates have been observed to be as high as 63.8% and therefore patients should receive a new baseline CT immediately following surgery (65,67). Petersen et al. observed a 5% rate of repeat metastasectomy, but no significant difference in survival between patients who underwent single versus repeat metastasectomy (61). Leo et al. observed a 19% 5-year survival rate in patients who underwent repeat metastasectomy for intra-thoracic disease recurrence alone (65). Thus, repeat metastasectomy is not absolutely contraindicated, given that the subsequent metastases are limited to the thorax and amenable to resection. Patients should continue close follow-up with a medical oncologist to determine the role for any adjuvant therapy.

Summary

PM for melanoma patients should be considered in patients with a small number (fewer than 3) of completely resectable pulmonary nodules, no evidence of extrathoracic disease or lymph node metastases, a DFI of greater than 1 year, and a demonstrated response to systemic therapy. Tumor doubling time of greater than 60 days is also a favorable prognostic indicator. Minimally invasive resection is reasonable in patients who underwent preoperative high-resolution and PET-CT scans, with peripherally located nodules. Wedge resection is acceptable for patients given that complete resection with negative margins is possible. Lymph node sampling and/or dissection is reasonable in order to further define patient prognosis.


Conclusions

For soft tissue sarcoma, breast cancer, and melanoma, a minimally invasive approach to PM is likely appropriate for select patients. Several studies for all three groups of malignancy suggest that minimally invasive PM is acceptable for small, peripherally located tumors. No studies were identified that demonstrated inferior overall survival or disease-free survival with a minimally invasive approach. The most common type of resection for all three malignancies was wedge resection, which is appropriate given that R0 resection is achievable. Larger tumors or those that are centrally located may require more extensive resection, such as segmentectomy or lobectomy. Historically, the common rationale for performing metastasectomy via thoracotomy was that this approach allowed for manual palpation of lung parenchyma by the surgeon. However, techniques have been described with a minimally invasive approach that allow for manual palpation of nearly the entire lung. Additionally, modern improvements in imaging may allow for detection of occult pulmonary disease that was not previously possible. For all three groups of malignancy, the role of thoracic lymph node dissection and/or sampling remains controversial. When it is performed, it is likely more useful for further defining patient prognosis rather than having any therapeutic effect. Importantly, for soft tissue sarcoma, breast cancer, and melanoma, studies directly comparing the outcomes and efficacy of minimally invasive PM to PM via thoracotomy are limited and often have very small sample sizes. This is a topic worthwhile of future study and any additional reports would be of benefit to the literature.


Acknowledgments

Funding: None.


Footnote

Provenance and Peer Review: This article was commissioned by the Guest Editors (Anthony W. Kim and Takashi Harano) for the series “The Role of Minimally Invasive Approaches in the Pulmonary Oligometastases” published in Video-Assisted Thoracic Surgery. The article has undergone external peer review.

Reporting Checklist: The authors have completed the Narrative Review reporting checklist. Available at https://vats.amegroups.com/article/view/10.21037/vats-23-46/rc

Peer Review File: Available at https://vats.amegroups.com/article/view/10.21037/vats-23-46/prf

Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at https://vats.amegroups.com/article/view/10.21037/vats-23-46/coif). The series “The Role of Minimally Invasive Approaches in the Pulmonary Oligometastases” was commissioned by the editorial office without any funding or sponsorship. The authors have no other conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.


References

  1. Sudarshan M, Murthy SC. Current Indications for Pulmonary Metastasectomy. Surg Oncol Clin N Am 2020;29:673-83. [Crossref] [PubMed]
  2. Kondo H, Okumura T, Ohde Y, et al. Surgical treatment for metastatic malignancies. Pulmonary metastasis: indications and outcomes. Int J Clin Oncol 2005;10:81-5. [Crossref] [PubMed]
  3. Kon Z, Martin L. Resection for thoracic metastases from sarcoma. Oncology (Williston Park) 2011;25:1198-204. [PubMed]
  4. Pastorino U, Buyse M, Friedel G, et al. Long-term results of lung metastasectomy: prognostic analyses based on 5206 cases. J Thorac Cardiovasc Surg 1997;113:37-49. [Crossref] [PubMed]
  5. Coindre JM, Terrier P, Guillou L, et al. Predictive value of grade for metastasis development in the main histologic types of adult soft tissue sarcomas: a study of 1240 patients from the French Federation of Cancer Centers Sarcoma Group. Cancer 2001;91:1914-26. [Crossref] [PubMed]
  6. Stamenovic D, Hohenberger P, Roessner E. Pulmonary metastasectomy in soft tissue sarcomas: a systematic review. J Thorac Dis 2021;13:2649-60. [Crossref] [PubMed]
  7. Gusho CA, Seder CW, Lopez-Hisijos N, et al. Pulmonary metastasectomy in bone and soft tissue sarcoma with metastasis to the lung. Interact Cardiovasc Thorac Surg 2021;33:879-84. [Crossref] [PubMed]
  8. Billingsley KG, Burt ME, Jara E, et al. Pulmonary metastases from soft tissue sarcoma: analysis of patterns of diseases and postmetastasis survival. Ann Surg 1999;229:602-10; discussion 610-2. [Crossref] [PubMed]
  9. Casson AG, Putnam JB, Natarajan G, et al. Five-year survival after pulmonary metastasectomy for adult soft tissue sarcoma. Cancer 1992;69:662-8. [Crossref] [PubMed]
  10. von Mehren M, Kane JM, Agulnik M, et al. Soft Tissue Sarcoma, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw 2022;20:815-33. [Crossref] [PubMed]
  11. Chudgar NP, Brennan MF, Munhoz RR, et al. Pulmonary metastasectomy with therapeutic intent for soft-tissue sarcoma. J Thorac Cardiovasc Surg 2017;154:319-330.e1. [Crossref] [PubMed]
  12. Smith R, Pak Y, Kraybill W, et al. Factors associated with actual long-term survival following soft tissue sarcoma pulmonary metastasectomy. Eur J Surg Oncol 2009;35:356-61. [Crossref] [PubMed]
  13. van Geel AN, Pastorino U, Jauch KW, et al. Surgical treatment of lung metastases: The European Organization for Research and Treatment of Cancer-Soft Tissue and Bone Sarcoma Group study of 255 patients. Cancer 1996;77:675-82. [Crossref] [PubMed]
  14. Sardenberg RA, Figueiredo LP, Haddad FJ, et al. Pulmonary metastasectomy from soft tissue sarcomas. Clinics (Sao Paulo) 2010;65:871-6. [Crossref] [PubMed]
  15. García Franco CE, Algarra SM, Ezcurra AT, et al. Long-term results after resection for soft tissue sarcoma pulmonary metastases. Interact Cardiovasc Thorac Surg 2009;9:223-6. [Crossref] [PubMed]
  16. 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;87:260-8. [Crossref] [PubMed]
  17. Pastorino U. History of the surgical management of pulmonary metastases and development of the International Registry. Semin Thorac Cardiovasc Surg 2002;14:18-28. [Crossref] [PubMed]
  18. Rehders A, Hosch SB, Scheunemann P, et al. Benefit of surgical treatment of lung metastasis in soft tissue sarcoma. Arch Surg 2007;142:70-5; discission 76.
  19. Kim S, Ott HC, Wright CD, et al. Pulmonary resection of metastatic sarcoma: prognostic factors associated with improved outcomes. Ann Thorac Surg 2011;92:1780-6; discussion 1786-7. [Crossref] [PubMed]
  20. Mutsaerts EL, Zoetmulder FA, Meijer S, et al. Outcome of thoracoscopic pulmonary metastasectomy evaluated by confirmatory thoracotomy. Ann Thorac Surg 2001;72:230-3. [Crossref] [PubMed]
  21. Gossot D, Radu C, Girard P, et al. Resection of pulmonary metastases from sarcoma: can some patients benefit from a less invasive approach? Ann Thorac Surg 2009;87:238-43. [Crossref] [PubMed]
  22. Lin AY, Kotova S, Yanagawa J, et al. Risk stratification of patients undergoing pulmonary metastasectomy for soft tissue and bone sarcomas. J Thorac Cardiovasc Surg 2015;149:85-92. [Crossref] [PubMed]
  23. Reza J, Sammann A, Jin C, et al. Aggressive and minimally invasive surgery for pulmonary metastasis of sarcoma. J Thorac Cardiovasc Surg 2014;147:1193-200; discussion 1200-1. [Crossref] [PubMed]
  24. Predina JD, Puc MM, Bergey MR, et al. Improved survival after pulmonary metastasectomy for soft tissue sarcoma. J Thorac Oncol 2011;6:913-9. [Crossref] [PubMed]
  25. Cerfolio RJ, McCarty T, Bryant AS. Non-imaged pulmonary nodules discovered during thoracotomy for metastasectomy by lung palpation. Eur J Cardiothorac Surg 2009;35:786-91; discussion 791. [Crossref] [PubMed]
  26. Gherzi L, Ferrari M, Pardolesi A. Lung metastases from sarcoma: multidisciplinary approach—a narrative review. AME Surg J 2022;2:38. [Crossref]
  27. Digesu CS, Wiesel O, Vaporciyan AA, et al. Management of Sarcoma Metastases to the Lung. Surg Oncol Clin N Am 2016;25:721-33. [Crossref] [PubMed]
  28. Azari F, Kennedy GT, Zhang K, et al. Impact of Intraoperative Molecular Imaging after Fluorescent-Guided Pulmonary Metastasectomy for Sarcoma. J Am Coll Surg 2022;234:748-58. [Crossref] [PubMed]
  29. Gafencu DA, Welter S, Cheufou DH, et al. Pulmonary metastasectomy for sarcoma-Essen experience. J Thorac Dis 2017;9:S1278-81. [Crossref] [PubMed]
  30. Dudek W, Schreiner W, Mykoliuk I, et al. Pulmonary metastasectomy for sarcoma-survival and prognostic analysis. J Thorac Dis 2019;11:3369-76. [Crossref] [PubMed]
  31. Markowiak T, Dakkak B, Loch E, et al. Video-assisted pulmonary metastectomy is equivalent to thoracotomy regarding resection status and survival. J Cardiothorac Surg 2021;16:84. [Crossref] [PubMed]
  32. Veronesi G, Petrella F, Leo F, et al. Prognostic role of lymph node involvement in lung metastasectomy. J Thorac Cardiovasc Surg 2007;133:967-72. [Crossref] [PubMed]
  33. Özdil A, Tekneci AK, Dökümcü Z, et al. Pulmonary Metastasectomy of Sarcoma: Is the Ratio of Surgical Margin to Nodule Size a Prognostic Factor? Thorac Cardiovasc Surg 2019;67:675-82. [Crossref] [PubMed]
  34. Higashiyama M, Tokunaga T, Nakagiri T, et al. Pulmonary metastasectomy: outcomes and issues according to the type of surgical resection. Gen Thorac Cardiovasc Surg 2015;63:320-30. [Crossref] [PubMed]
  35. Fong Y, Coit DG, Woodruff JM, et al. Lymph node metastasis from soft tissue sarcoma in adults. Analysis of data from a prospective database of 1772 sarcoma patients. Ann Surg 1993;217:72-7. [Crossref] [PubMed]
  36. Chudgar NP, Brennan MF, Tan KS, et al. Is Repeat Pulmonary Metastasectomy Indicated for Soft Tissue Sarcoma? Ann Thorac Surg 2017;104:1837-45. [Crossref] [PubMed]
  37. Siegel RL, Miller KD, Fuchs HE, et al. Cancer statistics, 2022. CA Cancer J Clin 2022;72:7-33. [Crossref] [PubMed]
  38. Soh J, Komoike Y, Mitsudomi T. Surgical therapy for pulmonary metastasis of breast cancer. Transl Cancer Res 2020;9:5044-52. [Crossref] [PubMed]
  39. Largillier R, Ferrero JM, Doyen J, et al. Prognostic factors in 1,038 women with metastatic breast cancer. Ann Oncol 2008;19:2012-9. [Crossref] [PubMed]
  40. Nesbit EG, Donnelly ED, Strauss JB. Treatment Strategies for Oligometastatic Breast Cancer. Curr Treat Options Oncol 2021;22:94. [Crossref] [PubMed]
  41. Carlson RW, Allred DC, Anderson BO, et al. Invasive breast cancer. J Natl Compr Canc Netw 2011;9:136-222. [Crossref] [PubMed]
  42. Rashid OM, Takabe K. The evolution of the role of surgery in the management of breast cancer lung metastasis. J Thorac Dis 2012;4:420-4. [PubMed]
  43. Yhim HY, Han SW, Oh DY, et al. Prognostic factors for recurrent breast cancer patients with an isolated, limited number of lung metastases and implications for pulmonary metastasectomy. Cancer 2010;116:2890-901. [Crossref] [PubMed]
  44. Fan J, Chen D, Du H, et al. Prognostic factors for resection of isolated pulmonary metastases in breast cancer patients: a systematic review and meta-analysis. J Thorac Dis 2015;7:1441-51. [PubMed]
  45. Diaz-Canton EA, Valero V, Rahman Z, et al. Clinical course of breast cancer patients with metastases confined to the lungs treated with chemotherapy. The University of Texas M.D. Anderson Cancer Center experience and review of the literature. Ann Oncol 1998;9:413-8. [Crossref] [PubMed]
  46. Endoh M, Shiono S, Yamauchi Y, et al. Pulmonary metastasectomy for pulmonary metastasis of breast cancer has a limited prognostic impact: a multi-institutional retrospective analysis. J Thorac Dis 2020;12:6552-62. [Crossref] [PubMed]
  47. Chen F, Fujinaga T, Sato K, et al. Clinical features of surgical resection for pulmonary metastasis from breast cancer. Eur J Surg Oncol 2009;35:393-7. [Crossref] [PubMed]
  48. Friedel G, Pastorino U, Ginsberg RJ, et al. Results of lung metastasectomy from breast cancer: prognostic criteria on the basis of 467 cases of the International Registry of Lung Metastases. Eur J Cardiothorac Surg 2002;22:335-44. [Crossref] [PubMed]
  49. Rena O, Papalia E, Ruffini E, et al. The role of surgery in the management of solitary pulmonary nodule in breast cancer patients. Eur J Surg Oncol 2007;33:546-50. [Crossref] [PubMed]
  50. Meimarakis G, Rüttinger D, Stemmler J, et al. Prolonged overall survival after pulmonary metastasectomy in patients with breast cancer. Ann Thorac Surg 2013;95:1170-80. [Crossref] [PubMed]
  51. Handy JR, Bremner RM, Crocenzi TS, et al. Expert Consensus Document on Pulmonary Metastasectomy. Ann Thorac Surg 2019;107:631-49. [Crossref] [PubMed]
  52. Mangiameli G, Cioffi U, Alloisio M, et al. Lung Metastases: Current Surgical Indications and New Perspectives. Front Surg 2022;9:884915. [Crossref] [PubMed]
  53. Kreisman H, Wolkove N, Finkelstein HS, et al. Breast cancer and thoracic metastases: review of 119 patients. Thorax 1983;38:175-9. [Crossref] [PubMed]
  54. Seebacher G, Decker S, Fischer JR, et al. Unexpected lymph node disease in resections for pulmonary metastases. Ann Thorac Surg 2015;99:231-6. [Crossref] [PubMed]
  55. Macherey S, Mallmann P, Malter W, et al. Lung Metastasectomy for Pulmonary Metastatic Breast Carcinoma. Geburtshilfe Frauenheilkd 2017;77:645-50. [Crossref] [PubMed]
  56. Detterbeck FC, Grodzki T, Gleeson F, et al. Imaging requirements in the practice of pulmonary metastasectomy. J Thorac Oncol 2010;5:S134-9. [Crossref] [PubMed]
  57. Davis LE, Shalin SC, Tackett AJ. Current state of melanoma diagnosis and treatment. Cancer Biol Ther 2019;20:1366-79. [Crossref] [PubMed]
  58. Deboever N, Feldman HA, Hofstetter WL, et al. The Role of Surgery in the Treatment of Melanoma Pulmonary Metastases in the Modern Era. J Surg Res 2022;277:125-30. [Crossref] [PubMed]
  59. Bong CY, Smithers BM, Chua TC. Pulmonary metastasectomy in the era of targeted therapy and immunotherapy. J Thorac Dis 2021;13:2618-27. [Crossref] [PubMed]
  60. Gamboa AC, Lowe M, Yushak ML, et al. Surgical Considerations and Systemic Therapy of Melanoma. Surg Clin North Am 2020;100:141-59. [Crossref] [PubMed]
  61. Petersen RP, Hanish SI, Haney JC, et al. Improved survival with pulmonary metastasectomy: an analysis of 1720 patients with pulmonary metastatic melanoma. J Thorac Cardiovasc Surg 2007;133:104-10. [Crossref] [PubMed]
  62. Viehof J, Livingstone E, Loscha E, et al. Prognostic factors for pulmonary metastasectomy in malignant melanoma: size matters. Eur J Cardiothorac Surg 2019;56:1104-9. [Crossref] [PubMed]
  63. Schuhan C, Muley T, Dienemann H, et al. Survival after pulmonary metastasectomy in patients with malignant melanoma. Thorac Cardiovasc Surg 2011;59:158-62. [Crossref] [PubMed]
  64. Harpole DH Jr, Johnson CM, Wolfe WG, et al. Analysis of 945 cases of pulmonary metastatic melanoma. J Thorac Cardiovasc Surg 1992;103:743-8; discussion 748-50. [Crossref] [PubMed]
  65. Leo F, Cagini L, Rocmans P, et al. Lung metastases from melanoma: when is surgical treatment warranted? Br J Cancer 2000;83:569-72. [Crossref] [PubMed]
  66. Essner R. Surgical treatment of malignant melanoma. Surg Clin North Am 2003;83:109-56. [Crossref] [PubMed]
  67. Okereke I. Surgical management of malignant melanoma of the lung. Melanoma Manag 2015;2:301-3. [Crossref] [PubMed]
  68. Chua TC, Scolyer RA, Kennedy CW, et al. Surgical management of melanoma lung metastasis: an analysis of survival outcomes in 292 consecutive patients. Ann Surg Oncol 2012;19:1774-81. [Crossref] [PubMed]
  69. Dalrymple-Hay MJ, Rome PD, Kennedy C, et al. Pulmonary metastatic melanoma -- the survival benefit associated with positron emission tomography scanning. Eur J Cardiothorac Surg 2002;21:611-4; discussion 614-5. [Crossref] [PubMed]
  70. Ollila DW, Stern SL, Morton DL. Tumor doubling time: a selection factor for pulmonary resection of metastatic melanoma. J Surg Oncol 1998;69:206-11. [Crossref] [PubMed]
  71. Andrews S, Robinson L, Cantor A, et al. Survival after surgical resection of isolated pulmonary metastases from malignant melanoma. Cancer Control 2006;13:218-23. [Crossref] [PubMed]
  72. Hanna TP, Chauvin C, Miao Q, et al. Clinical Outcomes After Pulmonary Metastasectomy for Melanoma: A Population-Based Study. Ann Thorac Surg 2018;106:1675-81. [Crossref] [PubMed]
  73. Mutsaerts EL, Zoetmulder FA, Meijer S, et al. Long term survival of thoracoscopic metastasectomy vs metastasectomy by thoracotomy in patients with a solitary pulmonary lesion. Eur J Surg Oncol 2002;28:864-8. [Crossref] [PubMed]
  74. Lo Faso F, Solaini L, Lembo R, et al. Thoracoscopic lung metastasectomies: a 10-year, single-center experience. Surg Endosc 2013;27:1938-44. [Crossref] [PubMed]
  75. Eckardt J, Licht PB. Thoracoscopic versus open pulmonary metastasectomy: a prospective, sequentially controlled study. Chest 2012;142:1598-602. [Crossref] [PubMed]
doi: 10.21037/vats-23-46
Cite this article as: Palleiko BA, Maxfield MW. Minimally invasive metastasectomy for skin and soft tissue malignancies: sarcomas, melanoma, and breast cancer: a narrative review. Video-assist Thorac Surg 2024;9:21.

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