Introduction
The management of lung metastases arising from head and neck tumors represents a complex clinical challenge. Over recent years, surgical interventions targeting these metastases have emerged as safe and effective procedures, characterized by low incidence of complications and mortality rates [1–6]. This has prompted a growing interest in exploring the outcomes and prognostic factors associated with pulmonary metastasectomy in this patient population. Despite advancements in surgical techniques and perioperative care, questions remain regarding optimal patient selection, treatment strategies, and long-term survival outcomes. Therefore, the aim of the current study is to provide a comprehensive investigation into the survival outcomes and prognostic factors following pulmonary metastasectomy for head and neck cancers. By analyzing a wide range of literature sources and considering the diverse clinical scenarios encountered in practice, this study seeks to contribute valuable insights that may inform evidence-based decision-making and optimize patient care in this challenging clinical context.
Methods
The study literature was systematically compiled through a comprehensive search of the Medline database. Utilizing the English-language text-based database PubMed, an exhaustive review of existing literature was conducted to identify relevant studies pertaining to the surgical management of lung metastases originating from head and neck cancers. It is noteworthy that the literature pertaining to potentially curative pulmonary metastasectomy for head and neck cancers is relatively sparse. Despite the limited availability of studies, efforts were made to capture the breadth of available evidence. The majority of identified studies were authored by institutions in Asia, particularly China and Japan, underscoring the global interest in this area of research [7–24].
Discussion
In patients with head and neck tumors, the incidence of lung metastases is significant, with approximately 53% of cases involving the lung and 13% affecting the pleura. Extrathoracic metastases play a pivotal role in influencing therapy and prognosis, significantly impacting overall survival. Given the complexity of disease presentation, treatment decisions necessitate a multidisciplinary assessment to determine the appropriate balance between palliative and potentially curative approaches. Despite the challenges posed by advanced disease, there has been a notable improvement in survival rates over recent decades [13, 25].
Ampil et al. reported notable findings regarding the efficacy of palliative radiotherapy in patients with mediastinal and pulmonary metastases, demonstrating a 1-year survival rate (1-YSR) of 39%, compared to a mere 4% 1-YSR in untreated patients [26]. Similarly, Bates et al. documented promising outcomes, with an 88% 1-YSR for patients undergoing stereotactic radiotherapy for lung metastases [27]. In a study by Wiegand et al., a collective analysis of patients treated with palliative chemotherapy, surgery, or radiotherapy revealed a 1-YSR and 2-YSR of 40.4% and 26.2%, respectively, underscoring the importance of multimodal therapeutic approaches [28].
Pointer et al. observed variations in survival outcomes based on the anatomical localization of head and neck cancers, with tumors situated in the nasal cavity and paranasal sinuses associated with better prognoses compared to those in the nasopharynx [29]. Moreover, Schulz et al. highlighted the adverse impact of metastatic spread to mediastinal lymph nodes, liver, and bone on median overall survival (2.63 months, 3.12 months, and 3.91 months, respectively), further compounded in patients with metastatic involvement across multiple organs or with multiple metastases [25, 29].
The presence of squamous cell carcinoma (SCC) emerged as a significant prognostic factor, with curatively resected SCC lung metastases from head and neck cancers exhibiting poor survival rates with a 5-YSR of 16.4%, as reported by Yotsukura et al. [15]. Unfortunately, SCC often presents at advanced stages, necessitating aggressive therapeutic strategies to mitigate disease progression [15, 30].
Notably, resectable lung metastases have shown improved survival outcomes. Winter et al. [13] demonstrated that patients undergoing surgical intervention had significantly higher survival rates compared to those receiving conservative treatment. This recommendation holds true even in cases of multiple or bilateral lung lesions, provided complete resection of metastases is feasible and there are no contraindications to extensive surgery, highlighting the importance of surgical precision in optimizing patient outcomes [13].
Five-year survival after pulmonary metastasectomy with curative intent
The literature demonstrates a wide range of 5-year survival rates (5-YSR) following pulmonary metastasectomy for various histological types and primary tumor localizations, emphasizing the substantial benefit of surgical resection. Wedman et al. reported a notably high 5-YSR of 59% following pulmonary metastasectomy for head and neck tumors, highlighting the significant survival advantage compared to the 4% 5-YSR observed in patients who did not undergo this procedure. These findings underscore the favorable prognosis associated with pulmonary metastasectomy in indicated cases of head and neck tumors [8].
Yamazaki et al. contributed valuable insights with their report of a 1-year survival rate of 79.4% [9]. Additionally, the noteworthy 3-year survival rate described by Nakajima et al. at 54.2% further supports the efficacy of pulmonary metastasectomy in achieving favorable long-term outcomes [10]. These findings collectively reinforce the importance of pulmonary metastasectomy as a crucial treatment option for head and neck cancers, offering the potential for significant improvements in relapse-free survival and overall patient prognosis.
Kuroda et al. reported a 5-year overall survival after complete pulmonary metastasectomy of 58.5%, 25.0%, and 46.9% in G1, 2, and 3, respectively [31]. A systematic review by Schlachtenberger et al. which included data deriving from 15 studies of patients undergoing metastasectomy demonstrated a 5-year survival rate varying from 21% to 59%, with median survival from 10 to 77 months after metastasectomy [32].
Table I summarizes the 5-YSR as reported in the literature.
Table I
Presentation of the 5-year survival after pulmonary metastasectomy described in the literature
| Study | Year | 5-year survival |
|---|---|---|
| Liu D. et al. [11] | 1999 | 50% |
| Winter H. et al. [13] | 2008 | 23% |
| Shiono S. et al. [12] | 2009 | 26.5% |
| Haro A. et al. [14] | 2009 | 50% |
| Yotsukura M et al. [15] | 2014 | 57.9% |
| Yamazaki K. et al. [9] | 2015 | 63.2% |
| Nakajima Y. et al. [10] | 2017 | 35.7% |
| Oki T. et al. [16] | 2019 | 54% |
| Kuroda H. et al. [31] | 2022 | 58.5% |
| Park H. et al. [33] | 2022 | 32.4–38.9% |
Analysis of prognostic survival factors after pulmonary metastasectomy for head and neck cancers
Localization of the primary tumor
The literature presents varying perspectives on the significance of primary tumor localization as a prognostic survival factor. While Shiono et al. [12] proposed that primary tumors located in the oral cavity may confer a positive prognostic influence, contrasting views have been expressed. Nibu et al.’s study from 1997 suggests that the prognosis of lung metastasectomy in head and neck cancers originating from the oral cavity depends closely on the histological characteristics of the primary tumor. Specifically, poorly differentiated epithelial carcinomas (PEC) originating from the oral cavities have been identified as unfavorable prognostic indicators [17]. Similarly, Haro et al. highlighted PEC originating from the oral cavity or pharynx as an unfavorable prognostic factor [14]. Kuroda et al. also demonstrated that poor prognostic factors for pulmonary metastasectomy from head and neck cancer included cancer originating in the oral cavity, tongue, and paranasal sinuses, as well as tumor size exceeding 20 mm [31]. However, some authors do not attribute significant prognostic value to the localization of the primary tumor, emphasizing the complexity of this aspect in predicting patient outcomes [13–16]. These contrasting perspectives underscore the need for further research to elucidate the precise role of primary tumor localization in predicting survival outcomes following pulmonary metastasectomy for head and neck cancers.
Histology of the primary tumor
SCC predominates among tumors arising in the head and neck region. Extensive investigations have sought to delineate its significance as a prognostic factor. Studies by Oki et al. [16], Chen et al. [18], and Yotsukura et al. [15] have consistently identified SCC as an unfavorable prognostic indicator. Patients with metastases from SCC have exhibited 5-YSR of up to 30% [11, 12]. Particularly concerning are the findings of Yotsukura et al. [15], who reported markedly diminished 5-year survival in patients undergoing lung metastasectomy for SCC head and neck cancers (16.4%) compared to other histological types (64.4%). However, the consensus is not unanimous, as studies by Winter et al. [13], Yamazaki et al. [9], and Nakajima et al. [10] did not find SCC to be statistically significant as a prognostic factor.
Conversely, adenoid cystic carcinoma (ACC) emerges as a notable positive prognostic survival factor in primary histology considerations. Yotsukura et al. [15] highlighted adenoid cystic tumors as the second most common tumor type. Adenoid cystic carcinomas, characterized by their relative rarity and slow growth, present a unique clinical profile. In a study by Liu et al. [11], patients with adenoid cystic carcinoma demonstrated a remarkable 5-YSR of 84%. However, the long-term prognosis poses a challenge, as Liu et al. [11] noted that all patients with adenoid cystic carcinoma eventually succumbed after 14 years. A recent report by Park et al. recorded 3-year and 5-year disease-free survival rates following metastasectomy of 49.9% and 39.9% for SCC and 38.9% and 32.4% for ACC, respectively [33]. These contrasting findings underscore the complex interplay between histological subtypes and their implications for survival outcomes following pulmonary metastasectomy for head and neck cancers.
Anatomical resections for lung metastases
Anatomical resections for lung metastases are imperative in pulmonary metastasectomy, emphasizing the importance of preserving maximal lung tissue. This approach is particularly crucial when considering potential re-operations for recurrent metastases, ensuring a substantial functional reserve and retaining the option for further surgical intervention. Various anatomical lung resection techniques, such as lobectomies, bilobectomies, segmentectomies, bisegmentectomies, and, in rare instances, pneumonectomy, may be warranted, especially in cases involving centrally located metastases.
When planning an anatomical resection, it is paramount to ascertain sufficient pulmonary reserve and the absence of clinical contraindications. Notably, Pfannschmidt et al. [34] observed that anatomical resections for lung metastases yielded a poorer 5-year survival outcome compared to wedge resections (25% versus 39%). This underscores the nuanced considerations required in selecting the appropriate surgical approach.
However, the literature presents conflicting findings regarding the necessity of lobectomy in head and neck cancers. Haro et al. [14] reported a 5-year survival rate of 45% among the 10 patients who underwent lobectomy in their study. These contradictory results underline the need for further research to elucidate the optimal surgical strategies in managing lung metastases originating from head and neck cancers.
It should, however, be clear that such anatomical resections are not the standard procedure for metastasectomies and are suitable only for selected cases. In light of contemporary surgical practices, it is important to acknowledge the role of less invasive techniques such as Nd-YAG laser resections, which are increasingly used worldwide for the treatment of lung metastases [1, 5, 24]. These procedures are often favored for their ability to preserve lung tissue and offer good long-term outcomes, particularly suitable for patients not amenable to more extensive surgery. While anatomical resections, such as lobectomies or segmentectomies, remain crucial for certain selected complex cases, the use of laser-assisted surgery provides a viable alternative that aligns with the principles of minimally invasive surgery and can be particularly beneficial in managing multiple metastases or in patients with limited pulmonary reserve [1].
Patient- and tumor-associated prognostic factors
Patient- and tumor-associated prognostic factors have been extensively explored in the literature, revealing several potential indicators of survival outcomes. Notably, age emerges as a significant prognostic factor, with patients under 60 years of age often exhibiting a more favorable prognosis. This observation is supported by studies conducted by Oki et al. and Haro et al., both of which identified age below 60 years as a positive prognostic survival factor [14, 16].
Another crucial prognostic factor is the disease-free interval (DFI) between 18 and 26 months. Oki et al. highlighted that a short DFI of less than 18 months is associated with an unfavorable prognosis [16]. Conversely, Nakajima reported a DFI of 24 months as a positive prognostic factor, leading to a 5-year survival rate of 69.8% [10]. Furthermore, Yotsukura et al. demonstrated that a DFI exceeding 26 months is associated with a significantly improved 5-year survival rate of 83.3% [15]. Park et al. identified a DFI less than 14 months and R1 resection as risk factors for recurrence in SCC, while a high T stage was a risk factor in ACC [33].
Incomplete resection of lung metastases (R1/R2-resection) is consistently identified as an unfavorable survival factor [19]. Studies by Yamazaki et al., Winter et al., Wedman et al., and Shiono et al. collectively support the notion that achieving a complete resection of lung metastases (R0 resection) is associated with a more favorable prognostic outcome [8, 9, 12, 13].
Primary tumor characteristics also play a crucial role in predicting survival outcomes. Oki et al. suggested that a primary tumor smaller than 2.5 cm may serve as a positive prognostic survival factor [16]. Additionally, Ferlito et al. proposed that primary tumors with an advanced T stage in the hypopharynx, oropharynx, or oral cavity are more likely to develop distant metastases [20]. However, primary tumor size, as investigated in studies by Nakajima et al., Yotsukura et al., Yamazaki et al., and Winter et al., did not consistently reach statistical significance as a prognostic survival factor [9, 10, 13, 15].
Table II presents an overview of positive prognostic survival factors identified in studies over the past 11 years, facilitating a comparative analysis with our study. This comprehensive examination underscores the multifactorial nature of prognostication in patients undergoing pulmonary metastasectomy for head and neck cancers.
Table II
Prognostic factors for survival after pulmonary metastasectomy for head and neck cancers
| Prognostic factor | Description | References |
|---|---|---|
| Age | Patients under 60 years of age may exhibit a more favorable prognosis | Oki et al. [16], Haro et al. [14] |
| Disease-free interval (DFI) | DFI falling between 18 and 26 months is associated with improved survival outcomes | Oki et al. [16], Nakajima et al. [10], Yotsukura et al. [15], Park et al. [33] |
| Completeness of resection | Complete resection of lung metastases (R0 resection) is associated with better survival | Yamazaki et al. [9], Winter et al. [13], Wedman et al. [8], Shiono et al. [12] |
| Primary tumor size | Tumor size may influence survival outcomes, with smaller tumors potentially indicating a better prognosis | Oki et al. [16], Nakajima et al. [10], Yotsukura et al. [15], Yamazaki et al. [9], Winter et al. [13] |
| Tumor histology | Squamous cell carcinoma (SCC) may be associated with poorer survival outcomes. Adenoid cystic carcinoma may indicate a better prognosis | Oki et al. [16], Chen et al. [18], Yotsukura et al. [15], Liu et al. [11], Park et al. [33] |
| Anatomical resection | The type of surgical resection (e.g., lobectomy, segmentectomy) may impact survival rates | Pfannschmidt et al. [34], Haro et al. [14] |
| Metastatic manifestations | Presence of metastases in multiple organs or multiple metastases may reduce survival rates | Schulz et al. [25] |
| Localization of primary tumor | The primary tumor‘s location may influence prognosis, although the findings are debated | Shiono et al. [12], Nibu et al. [17], Haro et al. [14], Kuroda et al. [31] |
This discussion highlights the multifaceted nature of prognostic factors impacting survival outcomes following pulmonary metastasectomy for head and neck cancers. While several factors such as age, completeness of resection, and disease-free interval have shown promising associations with improved survival, challenges persist, particularly regarding the influence of tumor histology and primary tumor localization. Future research endeavors should aim to further elucidate the complex interplay of these factors, potentially incorporating advancements in imaging modalities, molecular profiling, and targeted therapies. By refining our understanding of prognostic indicators and implementing multidisciplinary approaches, we can strive to optimize treatment strategies and enhance outcomes for patients with metastatic head and neck cancers.
Conclusions
Metastatic head and neck cancers frequently involve the lungs, presenting a significant challenge in clinical management. Pulmonary metastasectomy, undertaken with curative intent, represents a safe and potentially life-extending surgical intervention for select patients. This review underlines the importance of identifying prognostic factors that influence outcomes following this procedure. While advancements in surgical techniques and perioperative care have contributed to improved survival rates, the complex interplay of various factors such as tumor histology, primary tumor localization, and patient demographics necessitates further investigation. In future, continued research efforts are essential to refine our understanding of these prognostic factors and optimize treatment strategies. By integrating multidisciplinary approaches and leveraging emerging technologies, we can enhance the efficacy of pulmonary metastasectomy and ultimately improve outcomes for individuals with metastatic head and neck cancers.
