Outcomes and prognostic insights in primary tracheal cancer: a multicenter retrospective study

Introduction

Tracheal cancers are very rare, accounting for less than 0.1% of all respiratory system cancers and only 0.02–0.04% of all malignant tumors (1). The annual incidence is approximately 0.1 cases per 100,000 people (1). The most common histological types are squamous cell carcinoma (SCC) and adenoid cystic carcinoma (ACC), which together comprise over 75% of primary tracheal tumors in adults (2). SCC is strongly associated with tobacco smoking and is more prevalent in older men, whereas ACC has a more even gender distribution and can occur in younger patients. ACC is also characterized by submucosal and perineural spread, which makes complete surgical resection challenging (3-5).

The prognosis for patients with primary tracheal tumors remains poor. Five-year survival rates range from 8% to 34% for SCC, and 50–77% for ACC, reflecting differences in tumor biology and treatment response (2). Standard therapeutic approaches include radical surgical treatment with additional radiotherapy. However, complete surgical resection is feasible only in a limited number of patients (4,6).

Recently, an analysis of treatment outcomes at the Maria Sklodowska-Curie National Research Institute of Oncology in Warsaw included a retrospective evaluation of 89 patients with primary tracheal tumors treated between 2000 and 2016. SCC was the most prevalent histological type, being diagnosed in 56.2% of patients, whereas ACC was identified in 21.3%. The median overall survival (OS) was 46.1 months for patients who underwent radical treatment and 7.2 months for those receiving palliative care. In the radically treated group, the 5-year survival rate was 45.9% for patients not treated surgically and 76.9% for those undergoing surgical treatment (6).

The aim of this study is to evaluate the treatment outcomes of patients treated in recent years (between 2017 and 2022) due to primary tracheal tumors and to identify clinical and pathological factors influencing prognosis. An important aspect of the analysis is the comparison of current results with historical data, which allows us to assess the impact of changes in clinical practice on treatment results. The findings of this study may contribute to further optimization of therapy and a better personalization of treatment for this rare disease. We present this article in accordance with the STROBE reporting checklist (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2025-352/rc).

Methods

This retrospective analysis included patients with primary tracheal tumors treated at the National Research Institute of Oncology in Warsaw and Gliwice branch of the Institute, Poland, between January 2017 and December 2022. Patients were identified by searching the institutions’ cancer registries. We analyzed adults (≥18 years) diagnosed with primary tracheal tumors. Patients with tumors that may have originated from the larynx, main bronchus, or other organs were excluded. As tracheal neoplasms are not included in the classification systems of International Union Against Cancer (UICC) and American Joint Committee on Cancer (AJCC), the staging was performed retrospectively based on the available imaging results before qualification for treatment.

Data on demographics, clinicopathological variables (symptoms, smoking history, performance status, histological diagnosis and the extent of the tumor), and type of the treatment were extracted from medical records. Because of the heterogeneity of the study population, analyses were performed for the entire group as well as for subgroups, depending on the treatment intent (i.e., radical or palliative).

The observation was completed on 31 August 2024. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Institutional Review Board of the National Research Institute of Oncology (No. 30/2024, issued on March 21, 2024). In accordance with national guidelines, informed consent for the use of anonymized retrospective data was waived. National Research Institute of Oncology in Gliwice was informed and agreed to the study.

It is important to note that surgical procedures were performed in thoracic surgery departments outside of the reporting oncology centers. As such, the available clinical documentation was limited to postoperative reports and discharge summaries. This constraint should be considered when interpreting surgical data, especially regarding selection and intraoperative decision-making processes.

Statistical analysis

OS was calculated from the date of pathological diagnosis to the date of death from any cause or last follow-up. Survival probabilities were estimated using the Kaplan-Meier method. Differences between groups were compared using the log-rank test. The impact of clinicopathological variables on OS was assessed using univariate Cox proportional hazards models. All P values less than 0.05 were considered statistically significant. Confidence intervals (CIs) were calculated at the 95% level. All statistical analyses were conducted using R software (version 4.4.2; The R Foundation for Statistical Computing, Vienna, Austria).

Results

Study population

Thirty-one patients, presenting at the diagnosis between January 2017 and December 2022, were identified. Detailed patient characteristics are presented in Table 1.

Histology

The most commonly diagnosed histological type was SCC, identified in 16 out of 31 patients (52%), while ACC was observed in nine patients (29%). Other histological diagnoses were grouped under the category “other” for statistical purposes and were not further differentiated. These diagnoses included: non-small cell carcinoma—one case, large cell neuroendocrine carcinoma—one case, small cell carcinoma—two cases, alveolar soft part sarcoma—one case, inflammatory myofibroblastic tumor—one case.

The degree of differentiation was poorly documented and, therefore, not included in the analysis.

The majority (75%) of patients diagnosed with SCC were aged over 60 years. This tumor type was not observed in individuals under the age of 35 years. ACC, however, was more prevalent in the 36–59 years age group (89% of ACC diagnosed in younger patients). SCC was more commonly diagnosed in men (56%), while ACC was more frequently found in women (67%). Among 24 patients for whom smoking history was available, 92% of those with SCC were current or former smokers, whereas 71% of patients with ACC had never smoked.

The most commonly reported symptoms were dyspnea (35%) and cough (19%). Hemoptysis was observed as the initial symptom in 19% of patients with SCC but it was not present in any patients with ACC. The T-stage classification distribution varied between histological types. Metastatic involvement of lymph nodes was observed in SCC and other histological types. Distant metastases at diagnosis were detected in 10% of patients.

Treatment

The proportions of patients stratified by treatment intent across different histological types are illustrated in Figure 1.

Figure 1 Intention to treat in relation to histologic type. ACC, adenoid cystic carcinoma; SCC, squamous-cell carcinoma.

Five patients were classified as receiving the best supportive care (BSC) only and were not included in the chart.

Radical treatment

Surgery

Surgical resection was performed in nine out of 15 patients (60%) treated with curative intent, including six with ACC, one with SCC, and two with other histological types. Complete macroscopic and microscopic resection was achieved in three patients with ACC. Microscopic tumor involvement in postoperative pathology report (R1 resection) was identified in three patients with ACC and one with SCC. R2 resections (macroscopic positive margins) were performed in two patients with other histological types. One patient with ACC experienced a severe postoperative complication as poor wound healing.

Radiation therapy

Radiotherapy (RT) as a primary radical treatment was used in five patients (33%), all of whom had a diagnosis of SCC. In two patients, external beam RT (EBRT) was delivered with a total dose of 70 Gy. The remaining three patients received combined treatment—EBRT with total dose between 52 to 56 Gy and brachytherapy boost (total dose of 10 Gy in a single fraction). Conventional fractionation was applied in all cases of EBRT. No severe treatment-related toxicities were observed.

Postoperative RT was administered to six patients (five with ACC, one with SCC). Four of these patients had positive surgical margins. The treatment involved EBRT to total dose of 56 to 70 Gy. Among them, one patient had combined treatment—56 Gy delivered with EBRT and intratracheal brachytherapy (10 Gy in a single dose).

Chemoradiation therapy

Chemoradiotherapy (CRT) as the sole radical treatment was used in one patient diagnosed with a different histological tumor type—non-small-cell carcinoma. The treatment was administered concurrently and included chemotherapy with carboplatin and paclitaxel combined with radiotherapy to a total dose of 60 Gy.

Additionally, one patient with a different histological tumor type received adjuvant CRT following surgical treatment (R2 resection).

Disease recurrence

Disease recurrence was documented in five out of 15 patients (33%) treated with curative intent. Following recurrence, one patient received chemotherapy, one was referred to the BSC, and three patients were lost to follow-up. None of the patients lost to follow-up are alive.

Deaths

In the analyzed group, 22 patients (80%) had died. At the end of the follow-up period, nine patients were still alive (six with ACC, one with SCC, and two with other histological types). Among the surviving patients, seven were initially treated with radical intent, all of whom underwent surgical treatment.

Survival

The 5-year OS rate for the entire analyzed group was 24% (95% CI: 17–35%) and the 3-year OS rate was 34% (95% CI: 20–59%).

Univariate analysis indicated that sex, WHO performance status, N stage, M stage, and treatment intent significantly impacted OS. Histological type and T stage did not significantly influence survival. Detailed survival rates and P values for these factors are presented in Table 2. The results of these analyses are presented in the figures: cumulative probability of OS stratified by sex, WHO performance status, histological type, tumor stage, nodal status, and metastasis status are shown in Figure 2A-2F, while survival based on treatment intent is presented in Figure 3.

Figure 2 Cumulative probability of overall survival in the entire analyzed cohort of patients stratified by: (A) sex; (B) WHO performance status (0/1 vs. 2/3); (C) histological type (ACC, SCC, other); (D) tumor stage (T1 vs. T2); (E) nodal status (N0 vs. N1); (F) metastasis status (M0 vs. M1). ACC, adenoid cystic carcinoma; M0/M1, distant metastasis absent/present; N0/N1, no metastasis in the regional lymph nodes/present; SCC, squamous cell carcinoma; T1/T2, tumor confined to the trachea/tumor spreads beyond the trachea to adjacent structures and organs; WHO, World Health Organization.

Figure 3 Cumulative probability of overall survival in the entire analyzed cohort of patients based on treatment intent (radical vs. palliative/best supportive care). BSC, best supportive care.

Discussion

Primary tracheal tumors are a group of poorly understood neoplasms, primarily because of their low incidence. Additionally, tracheal tumors are diverse in terms of morphology and clinical course. These factors make it challenging to accurately predict the disease’s progression. In this study, we evaluated our experience and compared it with findings reported in previous publications. However, evaluating and comparing statistical analysis results is hindered by the aforementioned rarity and heterogeneity of tracheal tumors.

Prognostic factors

Sex

Information regarding the impact of sex on survival in patients diagnosed with tracheal tumors is limited and the data are conflicting. In a retrospective analysis of 30 patients with tracheal ACC, the 5-year OS rates for men and women were 92% and 77%, respectively, with the difference being statistically insignificant (P=0.345) (7). No statistically significant impact of sex on PFS and OS was demonstrated in a systematic review and analysis of data from 733 patients (8). In another study, women demonstrated better disease-specific survival (DSS), measured from the start of treatment to death due to tracheal cancer (P=0.044), but no significant impact on OS was observed (P=0.467) (9). A favorable impact of female sex on disease-free survival (DFS) was demonstrated in a study of patients with tracheal ACC treated surgically; however, no effect on OS was observed (10). A study by Hetnał et al. reported a favorable impact of female sex on OS, with 5-year OS rates of 7% for men and 32% for women (P=0.04) (11). Similar results were obtained in our previous study. The 5-year OS was 2.1% (95% CI: 0.3–14.5%) for men and 50.6% (95% CI: 37.2–68.7%) for women. Additionally, a survival benefit in terms of both OS and DFS was demonstrated for women treated with radical intent (12).

The observed differences in survival between genders may be due to several biological and clinical factors. Firstly, female sex may serve as a favorable prognostic factor because of hormonal differences that influence tumor biology. Estrogens can modify the tumor microenvironment, potentially affecting its progression. Secondly, differences in the etiology of tracheal cancers between sexes may also play a role. SCC of the trachea, strongly associated with smoking, is significantly more common in men who have historically been more exposed to long-term smoking. In contrast, ACC, which lacks such a strong link to tobacco use, occurs more frequently in women and is associated with better treatment outcomes. Additionally, disparities in treatment access and approaches may contribute. Women are more frequently subjected to radical treatment, which is linked to improved survival. Differences in treatment-seeking behavior cannot be excluded either. Women may be more likely to notice symptoms earlier and seek medical attention, increasing the likelihood of early diagnosis and effective treatment. Other factors are discussed in the authors’ previous work (12).

Female sex is clearly associated with better survival outcomes in primary tracheal tumors. However, further research is needed to fully understand the mechanisms underlying this phenomenon. It is also crucial to consider sex in analyses comparing the effectiveness of different treatment modalities.

Performance status

There are few studies analyzing the prognostic value of performance status in patients diagnosed with tracheal tumors (11,13-16). All of these studies assessed the value of RT as a standalone treatment for these tumors. In the study by Chao et al., which evaluated the role of RT in the treatment of tracheal tumor patients, impaired performance status was identified as a significant prognostic factor for worse survival. The study included 25 patients with a WHO performance status of 0–1 and 12 patients with a WHO performance status of 2–4. The 1- and 2-year OS rates for patients with WHO performance statuses of 0–1 and 2–4 were 48% and 8%, and 22% and 0%, respectively (P=0.007) (13). In the study by Napieralska et al., the 5-year OS rates for patients with a performance status of 0, 1, and 2 were 36%, 26%, and 0%, respectively (14). Similar results were obtained in the study by Jeremic et al. (15). Mornex et al. reported 1-, 2-, and 5-year OS rates of 57%, 37%, and 15%, respectively, for 34 patients with a WHO performance status of 0–1, compared to 31%, 12%, and 4% for 50 patients with a WHO performance status of 2–4 (P=0.01) (16). Hetnał et al. confirmed the above observations, demonstrating that a performance status greater than 80 on the Karnofsky scale is an independent prognostic factor for OS (P<0.001) (11).

Our results align with the literature, confirming the strong prognostic value of performance status. Importantly, patients with better PS (WHO 0–1) were significantly more likely to qualify for radical treatment, which correlates with improved survival outcomes. In contrast, patients with poorer PS (WHO 2–3) were limited to palliative approaches, further emphasizing the need for careful qualification for treatment based on PS.

Given the rarity of tracheal tumors, diagnostic challenges often lead to delays in detection, during which the general condition of the patient may deteriorate, negatively impacting PS. This highlights the critical importance of early diagnosis, which increases the likelihood of detecting the tumor before significant symptoms compromise the patient’s functional status. Faster diagnostics and broader awareness among clinicians can help identify these rare tumors at a stage when PS remains optimal, thereby expanding eligibility for radical treatment.

Efforts should focus on streamlining diagnostic pathways and improving awareness of tracheal tumors’ clinical presentation. Early detection and intervention are essential to improving outcomes, as PS is not only a prognostic factor but also a determinant of treatment eligibility.

Histological type

The results of this study did not demonstrate a significant impact of the histological type of primary tracheal tumors on patient survival. This finding is surprising in light of previous reports where histology was identified as one of the key prognostic factors.

However lack of correlation between survival and histology may be due to the disproportion in numbers of patients with SCC and ACC.

ACC is typically considered a tumor with a more favorable prognosis, owing to its slower growth, local invasiveness, and lower incidence of distant metastases in the early stages of the disease (2,4,9,11,14,17-25). These findings are consistent with recent data from a large retrospective series, in which the 5-year OS for ACC patients reached 77%, compared to 26.5% for SCC patients (26).

Numerous studies suggest that patients with ACC are more frequently eligible for radical surgical resection, which significantly improves survival outcomes. For patients undergoing complete surgical resection, the 5-year OS reaches the level of 86% (27). The potential benefit of adjuvant RT has also been noted (4,28). In contrast, the efficacy of radiotherapy for SCC is described as limited (8). Moreover, SCC is often diagnosed at more advanced stages, limiting the feasibility of radical treatment.

The retrospective nature of the analysis, data heterogeneity, and the lack of a standardized tumor-node-metastasis (TNM) classification system for tracheal tumors may have contributed to the underestimation of survival differences related to histology.

Nodal status

The results of the current retrospective analysis indicate that regional lymph node involvement (N1 status) significantly affected OS. Patients with N0 status achieved a 5-year OS rate of 40%, whereas no 5-year survivors were observed in the N1 group (P<0.001). In the authors’ previous study significantly worse 5-year OS was observed in cases of clinical lymph node involvement (overall group: 41% vs. 0%). These findings are consistent with other reports in the literature (2,9,11,18). In Bhattacharyya study, patients with positive regional lymph nodes had more than 50% worse survival compared to those with N0 status (18). Similarly, Gaissert et al. reported significantly worse survival outcomes in patients with lymph node involvement (N-positive) (4).

In cases of ACC, lymph node involvement is less common compared to SCC, reflecting the distinct growth patterns of these tumors (local invasion with fewer lymph node metastases). This could explain the better prognosis observed in ACC patients with N0 (29) compared to SCC (30). The literature also emphasizes the role of adjuvant therapy in N-positive cases, particularly RT, which may improve survival outcomes (4,17). However, the limited number of N1 patients in the analyzed cohort (7 out of 31) may have affected the statistical results.

The findings of this study confirm that regional lymph node involvement is a prognostic factor in primary tracheal tumors. The lack of 5-year survivors in this group highlights the necessity of evaluating intensified treatment strategies, including the use of adjuvant therapy. Due to the small sample size and patient heterogeneity, further studies are needed to better understand the impact of lymph node involvement on treatment outcomes.

Treatment

In the analyzed patient cohort, a significant improvement in OS was observed in patients treated with radical intent compared to those receiving palliative care (5-year OS: 36% vs. 0%; P=0.002). Among patients in the radical treatment group, 60% underwent surgical treatment, emphasizing the importance of resection as a key component of therapy.

In a previous study involving a larger cohort of patients (n=89), the median OS following radical treatment was 46 months, with 5-year survival reaching 77% among surgically treated patients (6). Numerous studies highlight that radical surgery is the optimal therapeutic option for primary tracheal tumors, particularly ACC (4,7,8,31,32). In Gaissert’s study, the 5-year OS rate following R0 resection reached as high as 86%. However, SCC patients, often diagnosed at advanced stages and associated with poorer prognoses, were less likely to qualify for resection (4).

Data from the literature suggest that more than half of patients with primary tracheal tumors could potentially be candidates for radical surgical treatment. However, due to the rarity of these tumors, limited clinical experience, and often delayed diagnosis, suboptimal treatment is frequently observed (24,27,33). A multidisciplinary audit of the Dutch Cancer Registry data found that among 50 cases of locally advanced tracheal cancer, surgical treatment was performed in only 24% of patients. A subsequent review identified an additional 16 patients who could have been eligible for surgery, raising the total to 56% (33). In our previous series, less than one third of patients (28.9%) underwent radical surgical treatment (6). Due to the retrospective nature of that study, it was not possible to determine whether the remaining patients received suboptimal care. Other factors may have influenced the decision to forgo surgery, but they were not documented. Nonetheless, the available data should prompt careful consideration of indications and contraindications for resection to ensure the most appropriate treatment. For this reason, management should be centralized in specialized centers, as treatment of tracheal tumors often requires the expertise of a multidisciplinary team. This approach could increase the number of patients qualified for surgical resection and potentially improve outcomes.

In the current series, we analyzed patients treated between 2017 and 2022, making this one of the most recent cohorts reported to date. Compared to our previous study, this updated analysis reflects recent changes in diagnostic accessibility and evolving therapeutic standards. Although radical surgery remains the cornerstone of curative treatment, it was still infrequently used—only 9 patients underwent surgery, and complete (R0) resection was achieved in 3 cases. This highlights that, despite improved awareness, surgical treatment continues to be underutilized, likely due to persistent diagnostic delays and limited referrals to high-volume centers.

In the current study, a significant proportion of SCC patients were treated with RT, whereas surgery was the preferred method for ACC cases. Delayed diagnosis of primary tracheal tumors, particularly SCC, results in a higher percentage of patients being eligible only for palliative care, where RT or supportive treatments are the sole options.

These findings confirm that radical treatment provides the best results. Further research is necessary to comprehensively evaluate the effectiveness of different treatment strategies, accounting for variations in histological types and disease stages. Additionally, these results underscore the need for standardized treatment protocols, particularly for palliative care patients, who are often underrepresented in studies. Palliative treatment of tracheal tumors has been described by the authors in a previous publication (34).

The prognosis for patients who cannot undergo radical treatment remains poor. The available literature and our observations do not allow for definitive conclusions about the effectiveness of various treatment strategies.

Study limitations

The major limitations of this study include the small sample size (n=31) and its retrospective nature, which are inherent to the rarity of primary tracheal tumors. These factors limit the ability to perform more advanced statistical analyses and draw conclusions regarding subgroups. This highlights the need for larger, multicenter studies to enhance the robustness of findings.

The patient population was heterogeneous, comprising various histological types of tracheal tumors (SCC, ACC and others), different stages of disease, and diverse treatment strategies. This heterogeneity complicates comparisons of treatment outcomes between subgroups and may influence the overall interpretation of results.

The treatment strategies applied to the analyzed cohort were also diverse, including surgery, RT, CRT and palliative care. The lack of standardized therapeutic protocols may have affected outcomes and limited comparability with other studies.

Another limitation is the lack of access to full surgical documentation. Since surgical procedures were performed in external thoracic surgery centers, detailed intraoperative findings and multidisciplinary decision-making records were not always available for review. This may have limited the ability to fully assess surgical selection criteria or technical variables (e.g., extent of resection, reconstruction methods), although postoperative oncological documentation allowed for reliable classification of surgical margins and intent.

A significant challenge lies in the absence of a unified TNM classification system for this group of tumors. This hinders detailed analyses and the ability to compare study results across centers. A standardized classification system could facilitate the assessment and qualification of patients for treatment and potentially help establish uniform recommendations for adjuvant therapy, particularly for patients with baseline lymph node involvement.

Despite these limitations, this study provides valuable insights into the treatment outcomes of primary tracheal tumors in two Polish oncological centers. The findings not only reinforce previously reported trends but also offer contemporary, real-world clinical data. This updated analysis presents a valuable opportunity to evaluate changes in treatment allocation and survival outcomes over time, and may contribute to the continued optimization of care pathways for this rare type of cancer.

The results highlight the need for larger, multicenter studies using standardized diagnostic and therapeutic protocols to improve our understanding of this rare and challenging group of tumors. Future research should also focus on the molecular and genetic profiling of tracheal tumors to uncover the biological differences between SCC and ACC. Such investigations may lead to the identification of novel biomarkers and therapeutic targets, ultimately supporting the development of more personalized treatment strategies.

Conclusions

The presented data aligns with the available literature, particularly regarding the better prognosis of patients with better performance status and those undergoing radical treatment.

Further multicenter studies are needed to better understand the biology of tracheal tumours and the effect of adjuvant therapy.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2025-352/rc

Data Sharing Statement: Available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2025-352/dss

Peer Review File: Available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2025-352/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2025-352/coif). D.M.K. reports serving on advisory boards for MSD, Roche, BMS, Takeda, Pfizer, Medison, AstraZeneca, Daiichi-Sankyo, Genmab, and Johnson & Johnson. The other authors have no 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. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Institutional Review Board of the National Research Institute of Oncology (No. 30/2024, issued on March 21, 2024). In accordance with national guidelines, informed consent for the use of anonymized retrospective data was waived. National Research Institute of Oncology in Gliwice was informed and agreed to the study.

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/.

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