Pulmonary metastasectomy: a 14-year single-center experience and literature review

Abstract

Background

Pulmonary metastasectomy (PM) is a commonly performed surgical procedure in selected patients with metastatic disease. The characteristics of patients undergoing PM and the spectrum of primary malignancies considered for surgical resection vary across institutions. We aim to provide a better understanding of current practice patterns by describing the characteristics and perioperative outcomes of patients who underwent PM at our institution.

Methods

We conducted a retrospective descriptive study of patients who underwent pulmonary metastasectomy between 2008 and 2022 at Ghaem Hospital, Mashhad, Iran. Demographic and clinicopathological data, including age, sex, primary tumor type, histology, and postoperative outcomes, were collected and analyzed.

Results

A total of 128 patients (mean age, 38.9 ± 18.0 years) were included in the analysis. The most common primary tumor sites were bone (25.8%) and soft tissue (16.4%), followed by head and neck (9.4%), colorectal (7.0%), and testicular (7.0%) malignancies. Sarcoma was the predominant histologic subtype (57.8%), followed by squamous cell carcinoma (11.7%), adenocarcinoma (10.9%), and germ cell tumors (7.8%). Postoperative complications included air leakage (n = 35), vascular injury requiring blood transfusion (n = 34), and one surgical site infection.

Conclusion

Pulmonary metastasectomy is performed in patients with a wide range of primary malignancies, with sarcoma representing the most common indication in our cohort. Review of the literature suggests that the role of pulmonary metastasectomy varies across different primary malignancies and depends on careful patient selection. Further prospective studies are needed to better define the clinical utility of pulmonary metastasectomy in different tumor types.

Introduction

Pulmonary metastasectomy (PM) is a widely practiced surgical approach for selected patients with metastatic disease. Patient selection for PM is guided by established criteria, including control of the primary tumor, absence of uncontrolled extrapulmonary disease, complete resectability of pulmonary metastases, adequate cardiopulmonary reserve, and the absence of a preferable systemic treatment option [1].

Although PM has been performed for decades, uncertainty remains regarding its role across different primary malignancies because outcomes are influenced by tumor biology and patient selection [2]. The primary tumor site is an important determinant of treatment strategy, recurrence patterns, and reported outcomes after PM [3]. For example, pulmonary metastases from prostate cancer are generally less amenable to complete resection and are associated with less favorable outcomes than those from colorectal cancer [4].

Numerous retrospective studies have evaluated PM in individual malignancies and have identified several prognostic factors associated with favorable outcomes. However, institutional experiences continue to provide valuable information regarding patient selection, tumor distribution, and perioperative outcomes in real-world clinical practice [3]. Furthermore, published data describing pulmonary metastasectomy from Middle Eastern centers remain limited [5–7]. Therefore, this study aimed to characterize the clinicopathological features and perioperative outcomes of patients undergoing PM at a tertiary referral center in Iran and to review the current literature to place these findings within the context of existing evidence. Characterizing local patient populations and surgical complications may contribute to a better understanding of current practice patterns.

Methods

This retrospective descriptive study includes all patients with lung metastasis who underwent PM between 2008 and 2022 at Ghaem Hospital in Mashhad, Iran. The data were collected by reviewing paper-based patient records. The patients were characterized by age, sex, complications, mass location, primary tumor source, and pathology. To review the articles, the search terms included, but were not limited to, pulmonary metastasectomy, soft tissue sarcoma, osteosarcoma, colorectal cancer, germ cell tumor, head and neck cancer, breast cancer, renal cell carcinoma, and uterine cancer. The review was conducted using PubMed/MEDLINE. Articles published in English addressing pulmonary metastasectomy in major tumor types were reviewed. Priority was given to systematic reviews, meta-analyses, randomized trials, and large retrospective studies. Case reports, conference abstracts, and non-English publications were generally excluded.

Statistical analysis

Data were analyzed using Microsoft Excel (Microsoft Corporation, Redmond, WA, USA). Continuous variables are presented as mean ± standard deviation (SD), while categorical variables are summarized as frequencies and percentages.

Results

A total of 139 patients underwent pulmonary metastasectomy at our institution between 2008 and 2022. Of these, 128 patients were included in the analysis, while 11 were excluded because of missing data. The mean age of the study population was 38.9 ± 18.0 years. Seventy-three patients (57.0%) were male, and 55 (43.0%) were female. Tumors were classified by histologic type and primary site. The major histologic categories were sarcoma (74 cases, 57.8%), squamous cell carcinoma (15 cases, 11.7%), adenocarcinoma (14 cases, 10.9%), and germ cell tumor (10 cases, 7.8%). Patients and tumor characteristics are summarized in Table 1. Postoperative complications included air leakage in 35 patients (27.3%). Intraoperative vascular injury requiring blood transfusion occurred in 34 patients (26.6%), and one patient (0.8%) developed a surgical site infection.

Table 1.

Baseline demographic and clinicopathological characteristics of patients undergoing pulmonary metastasectomy

Variable
Age
Mean ± standard deviation	38.9 ± 18.0 years
Sex	Number of patients (128)	Percent
Male	73	57.0%
Female	55	43.0%
Metastatic Mass Location
Unilateral lung	73	57%
Bilateral lung	36	28%
Lung & chest wall	8	6%
Chest wall	7	5%
Mediastinum & chest wall	2	2%
Other (not specified)	2	2%
Site of origin
bone	33	25.8%
Soft tissue	21	16.4%
Head and neck	12	9.4%
Colorectal	9	7.0%
Testicular	9	7.0%
Breast	7	5.5%
Kidney	3	2.3%
Uterus	3	2.3%
Other a	31	24.2%
Histology of Primary Tumor
Sarcoma	74	57.8%
Soft tissue sarcoma	30	23.4%
Osteosarcoma	24	18.8%
Ewing sarcoma	3	2.3%
Other types of sarcomas	17	13.3%
Squamous cell carcinoma	15	11.7%
Adenocarcinoma	14	10.9%
Germ cell tumor	10	7.8%
Other (not specified)	15	11.7%

a: Includes uncommon primary tumor sites and cases with unknown site of origin

Discussion

Based on our experience, bone and soft tissue tumors were the most common primary malignancies metastasizing to the lungs among those selected for PM. Other frequently encountered tumors included those from the head and neck, as well as colorectal, testicular, breast, renal, and uterine origins. These findings align with the results reported by Sadoff et al. and Younes et al., who analyzed cohorts of 6,732 and 529 patients, respectively [8, 9]. This finding may indicate tumors with more favorable features for metastasectomy.

Compared with the cohort reported by Cheung et al., colorectal cancer accounted for a smaller proportion of cases in our study, whereas sarcomas and germ cell tumors were relatively more frequent [1]. This difference may partly reflect the younger age of our patients (mean age 38.9 vs. 55 years), as colorectal cancer predominantly affects older adults, while sarcomas and germ cell tumors are more common in younger populations. Differences in institutional referral patterns and regional cancer epidemiology may also have contributed to the observed variation in tumor distribution.

Our experience also demonstrated that the majority of patients considered for PM presented with unilateral metastatic lesions. Although bilateral pulmonary involvement or concomitant chest wall metastases generally make a patient less favorable for surgical intervention, they do not necessarily preclude surgery. In line with our findings, previous studies have reported that approximately 41% of patients who underwent surgery presented with bilateral metastases [8].

Although approximately one-quarter of patients required intraoperative blood transfusion, this finding should not be interpreted as indicating a high incidence of major vascular injury. In our institutional database, this variable denoted the requirement for intraoperative blood transfusion secondary to blood loss rather than documented inadvertent injury to major intrathoracic vessels. Moreover, our cohort included patients who underwent technically demanding procedures, including combined pulmonary and chest wall resections, which are associated with greater operative complexity and blood loss.

Generally, tumor resectability, a long disease-free interval, and control of the primary tumor are widely recognized as prognostic factors across various tumor types [10]. However, studies have identified tumor-specific prognostic factors and differences in the effectiveness of PM that influence decisions regarding patient selection for surgery.

Sarcoma

Sarcoma is a cancer of mesenchymal origin that includes over 50 histological subtypes, classified as either bone or soft tissue tumors [2, 11]. The median overall survival time for osteosarcoma with lung metastasis is only about two years [12].

Despite the high mortality rate among patients with pulmonary metastasis, different studies have concluded the effectiveness of PM for sarcoma with pulmonary metastasis [2, 13–15]. Schur et al. stated that PM is a reasonable treatment as it is safe and provides a median overall survival of 45.3 months after the first surgery [13]. A systematic review of data from 1,196 patients who underwent PM for bone and soft tissue sarcomas revealed 5-year survival rates of 34% and 25%, respectively [2]. Another study involving 565 sarcoma patients with isolated pulmonary metastasis also found that surgery could extend the disease-free survival time from 20 months to 32 months [15].

Various studies have identified multiple prognostic factors for the survival outcome of PM. Disease-free periods of more than 12 [16, 17] or 24 [18, 19] months, metastatic lesion doubling time of more than 1 month [20], lung tumors smaller than 15 [19] or 20 [17] mm, minimally invasive resection [18], and age younger than 55 years [21] are associated with better survival outcomes after surgery. Research has offered contradictory findings about the prognostic effect of the number of pulmonary metastatic lesions. Smolle et al. demonstrated the benefits of surgery regardless of the number of pulmonary lesions [14], while other studies suggested that having more than 1 [18, 21] or 5 [19] lesions is associated with worse survival outcomes. Regarding primary tumor histology, leiomyosarcoma was associated with improved survival compared with other soft tissue sarcomas [15, 18].

In our experience, sarcoma accounted for the majority of pulmonary metastasis cases selected for PM. We observed no major complications following metastasectomy.

Head and neck cancers

The reported incidence of distant metastasis from head and neck cancers (HNCs) is 4.2–58.8%, and the lungs are the most common metastatic site [22, 23]. Despite advances in immunotherapy and chemotherapy, PM has remained the main treatment option for pulmonary metastasis from HNCs [24]. The 5-year overall survival rate after PM varied from 20.9% to 67.0% [23, 25]. The literature reported that the survival rate was significantly higher in patients who underwent surgery than in those who received conservative treatment [23, 26].

It has been reported that pulmonary metastasis from HNCs originating in the oral cavity or tongue is associated with poor outcomes [23, 27]. The histology of squamous cell carcinoma also negatively impacts the prognosis of patients [28, 29]. Other factors that can lead to poor outcomes include incomplete resection [23], short disease-free interval [23, 25, 29, 30], tumor size > 20 [27] or 25 [31] mm, recurrence before lung metastasis [31], stage IV primary cancer [30], male sex [29], and age > 60 years [28]. A systematic review by Schlachtenberger et al. found that patients with multiple bilateral pulmonary metastases may benefit from non-surgical treatments [22]. Twelve patients with head and neck cancers underwent PM at our institution. Their primary tumors arose from the thyroid gland, larynx, or skeletal muscle. No cases originated in the oral cavity or tongue, which are associated with poorer PM outcomes based on the literature.

Colorectal cancer

In 5–15% of patients with colorectal cancer (CRC), metastasis spreads to the lungs [32]. PM has emerged as a potential treatment for CRC patients with lung metastases. However, based on current evidence, PM does not necessarily correlate with better survival [33]. A growing body of evidence suggests that non-surgical treatments may offer better survival outcomes than previously assumed [34, 35]. The PulMiCC study, with 93 participants, is one of the few randomized clinical trials exploring PM’s impact on CRC patients. While the study does not demonstrate PM’s inferiority, it does question its widely perceived benefits [36]. Hence, in prospective studies, it is crucial to assess the actual effect of PM on outcomes and patient quality of life and compare it with non-surgical options.

A meta-analysis of a series published between 2000 and 2011 demonstrated four risk factors associated with poor survival outcomes following PM. They include short disease-free intervals (DFI) between primary tumor and metastatic disease, multiple pulmonary metastases, hilar or mediastinal lymph node metastasis, and elevated pre-thoracotomy carcinoembryonic antigen (CEA) level [37]. A more recent and comprehensive review of the literature published between 2000 and 2021 added the following criteria associated with better survival following PM in CRC patients: metastatic lesion < 2 cm, no history of hepatic or extra-thoracic metastasis, no history of chemotherapy before PM, CRC T stage < T4, no p-53 mutations, normal CEA before CRC resection and PM. This study also stated that DFI < or > 24 months is not associated with better or worse outcomes after PM [38].

Despite discrepancies in conclusions about the PM’s benefit, it remains a safe treatment option with suitable outcomes in patients with satisfactory prognostic factors. Among the nine patients with colorectal cancer who underwent PM at our institute, one developed air leakage, two had vascular injury, and two experienced both; none resulted in significant complications or persistent sequelae.

Germ cell tumors (GCTs)

Germ cell tumors (GCTs) originate from reproductive cells, usually in the testis and ovaries. Although GCTs are responsible for only 1% of malignancies in the general population, they are the most common neoplasms in young males aged between 15 and 35 [39]. In almost 20% of cases of testicular germ cell tumors, there is a systemic metastasis. However, due to their sensitivity to radiation and chemotherapy, these types of tumors are associated with promising treatment outcomes.

A cisplatin-based chemotherapy regimen is the first line of treatment in GCTs [40]. PM is advised after the completion of chemotherapy and normalization of serum tumor markers [41]. The studies reported PM as a safe and efficient treatment option for residual disease following chemotherapy. The reported mortality rate following PM is up to 2%, while its 5-year survival ranges between 42% and 95%. The defined indication for performing PM in GCT cases is not limited to patients with favorable responses to chemotherapy. Patients with no response, partial response, or recurrences also benefit from the surgery. PM is also indicated to differentiate viable tissue from fibrosis/necrosis following chemotherapy [42].

The reported prognostic factors associated with favorable outcomes include long DFI, complete resection, absence of extrapulmonary metastasis, lower tumor marker levels before the surgery, and presence of fibrosis or mature teratoma on the resected pulmonary lesion [40, 42–44]. Stoleriu et al. mentioned that intrathoracic lymph node involvement, chest wall metastasis, metachronous metastasis, and embryonal carcinoma could lead to worse surgical outcomes [45]. We performed PM on 10 patients with germ cell tumors. Nine had testicular primaries, and one had choriocarcinoma. Only two patients had bilateral pulmonary involvement, and one had chest wall disease. The remaining seven patients had unilateral lung metastases, which aligns with previously reported favorable prognostic factors.

Breast cancer

Breast cancer is one of the most common cancers in women, with a high risk of metastasis to distant organs, including the lungs. Approximately 12% of breast cancer patients experience pulmonary metastasis, often years after their initial cancer diagnosis [46].

The efficacy of PM for breast cancer patients with lung metastasis is controversial, with studies yielding mixed results regarding its benefits. A systematic review by Fan et al. has an optimistic view of PM as a promising treatment for pulmonary metastasis in patients with breast cancer. They report a pooled 5-year survival rate of 46% after PM and consider it a “relatively high overall survival rate.” [46] In contrast, a multi-institutional retrospective analysis by Endoh et al. believes that PM has limited efficacy in this group of patients and should be considered an optional treatment [47].

Adverse prognostic factors following PM in breast cancer patients include DFI < 3 years [46, 47], large tumor size [47], number of pulmonary metastases > 1 [46], incomplete resection [46], lymph node involvement [47], and negative hormone receptor status [46]. Among seven patients with breast cancer who were selected for PM at our institute, one patient had mediastinal and chest wall involvement. Other patients had unilateral pulmonary metastasis. Careful patient selection based on prognostic factors may improve PM efficacy in extending survival.

Renal cell carcinoma

Renal cell carcinoma (RCC) is responsible for 2–3% of malignancies, making it a relatively uncommon tumor [48]. However, 25–30% of patients with RCC have metastatic lesions at the time of diagnosis, and the lungs are among the most commonly affected organs [49, 50].

The 5-year survival rate for patients with RCC metastasis has been reported to be between 0% and 18%, whereas for patients who undergo PM, it may increase from 21% to 75% [49]. Although the favorable outcomes of PM are highly dependent on tumor characteristics, different studies confirm that surgical resection provides a significant survival advantage over untreated patients [51, 52].

Most studies agree that complete resection is the most important predictor of PM outcome in RCC patients [52, 53]. A systematic review involving 1447 patients highlighted short DFI, lymph node involvement, multiple metastases, larger metastases, and synchronous metastases as predictors of poor survival outcomes after PM ⁵¹. There is debate on the effect of primary tumor histology on the outcomes. A study by Ohtaki et al. demonstrated the favorable impact of clear cell tumors [48]. In contrast, another study mentioned that the subtype of RCC (clear cell, papillary, chromophobe, cystic-solid, medullary) does not affect the outcomes [53].

Uterine cancer

Metastasis of uterine malignancy to the lungs is relatively rare, with an incidence of 2.3%- 4.6% [54]. PM is considered a safe and acceptable treatment option. The 5-year survival rate in patients selected for PM is 46.8%- 68.8% [54–58]. A study on 319 patients stated that surgical indications should be established based on prognostic factors for each histology [58]. In uterine adenocarcinoma, a disease-free interval of more than 12 months is associated with better outcomes, while tumor size and number may not be critical factors. For squamous cell carcinoma, metastasectomy can be considered more liberally, as neither DFI nor tumor size is a strict limitation, though the overall prognostic benefit remains uncertain. In contrast, sarcoma exhibits a more aggressive pattern, where increased tumor size and number correlate with a higher mortality risk, requiring careful patient selection [58]. Other studies, however, with smaller sample sizes, suggested the following as poor prognostic factors: DFI < 24 [55, 56, 59] or 12 [57] months, number of metastases > 3 [54, 57], tumor size > = 3 cm [57], primary tumor in the cervix [55, 57], pulmonary symptoms [54], and recurrence after PM [59].

Discrepancies in reported prognostic factors and surgery effectiveness across various studies arise from differences in study design, patient selection, tumor characteristics, treatment variability, data limitations, and statistical methods.

This study has several limitations. First, the retrospective design relied on paper-based medical records collected over 14 years, resulting in missing data for some patients and variables. Consequently, 11 patients were excluded from the analysis, and incomplete documentation limited the availability of certain clinical and pathological information. Moreover, this lack of data prevented survival analysis. Second, as a single-center study, the findings may be influenced by institutional referral patterns and patient selection, which may limit their generalizability to other centers and populations. Third, the relatively small number of patients with primary malignancies other than sarcoma limited our ability to perform detailed stratified analyses according to primary tumor site or histologic subtype. Consequently, comparisons between different tumor types within our cohort should be interpreted with caution. Finally, although this study provides valuable descriptive data from an underrepresented geographic region, larger prospective, preferably multicenter studies with standardized data collection are needed to better define the patients who derive the greatest benefit from pulmonary metastasectomy and to validate these findings.

Conclusion

Pulmonary metastasectomy is performed in patients with a wide range of primary malignancies, with sarcoma representing the most common indication in our cohort. Review of the literature suggests that the role of pulmonary metastasectomy varies across different primary malignancies and depends on careful patient selection. Further prospective studies are needed to better define the clinical utility of pulmonary metastasectomy in different tumor types.

Author contributions

R.D. and A.M. wrote the main manuscript text. H.S. collected and analyzed patient data. G.A. performed the literature review and contributed to drafting the discussion. H.F. supervised the study, revised the manuscript critically for important intellectual content, and approved the final version. All authors reviewed and approved the final manuscript.

Funding

This study received no financial support.

Data availability

The datasets generated and analyzed during the current study are not publicly available due to institutional and patient privacy considerations but are available from the corresponding author on reasonable request.

Declarations

AI disclosure statement

The authors confirm that all scientific content, including the study design, literature interpretation, data analysis, results, and conclusions, was developed entirely by the authors. During manuscript preparation, ChatGPT (OpenAI) was used solely to improve the language, grammar, clarity, and readability of the text through editing and rephrasing. No artificial intelligence tool was used to generate scientific content, analyze data, interpret findings, or formulate conclusions. All AI-assisted edits were carefully reviewed, verified, and revised by the authors, who accept full responsibility for the accuracy, originality, and integrity of the final manuscript.

Consent statement

Written informed consent was obtained from the patient to publish this report in accordance with the journal's patient consent policy.

Competing interests

The authors declare no competing interests.