Clinical characteristics and treatment challenges of esophageal sarcomatoid carcinoma: a single-center retrospective cohort study

Introduction

Esophageal cancer (EC) is one of the malignant tumors that currently poses a serious threat to human health. It is a highly prevalent and deadly malignancy, with an estimated 511,000 new cases and 445,000 deaths globally in 2022 (1). China, as one of the countries with a high incidence of EC, reported 224,012 new cases and 187,467 deaths in 2022, ranking seventh and fifth respectively in the national cancer morbidity and mortality spectrum (2). The common pathological types of EC in China are squamous cell carcinoma (SCC) and adenocarcinoma (AC), with SCC being significantly more prevalent, accounting for over 90% of all EC cases (2). Esophageal sarcomatoid carcinoma (ESC) is a rare malignant tumor characterized by the coexistence of carcinomatous and sarcomatous components, accounting for only 0.5–2.8% of all esophageal cancers (3). The World Health Organization (WHO) classifies ESC as spindle cell SCC, featuring a biphasic pattern of tumor squamous epithelium and spindle cells (4).

Currently, research on ESC primarily consists of small-sample studies or case reports (5). Due to its extremely low incidence, it is challenging to conduct large-scale studies to investigate its clinical characteristics and prognostic factors. This study retrospectively analyzes 57 ESC patients who underwent radical surgical treatment at the Cancer Hospital, Chinese Academy of Medical Sciences. By investigating a relatively large cohort, this research aims to explore the clinical features and prognostic factors of ESC patients. We present this article in accordance with the STROBE reporting checklist (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1149/rc).

Methods

Patients and clinical data

This retrospective study collected clinical data of 57 patients with ESC who underwent surgical treatment at the Cancer Hospital, Chinese Academy of Medical Sciences between January 2000 and December 2021. The data included sex, age, body mass index (BMI), smoking history, alcohol consumption, months between onset to treatment, family history of cancer, comorbidities, tumor size, tumor location, macroscopic tumor type, T stage, number of lymph nodes dissected, lymph node status, tumor node metastasis (TNM) stage, and treatment modalities.

Inclusion criteria were: patients who underwent radical surgery; primary ESC confirmed by histopathology. Exclusion criteria were: patients who refused follow-up; incomplete medical records. The TNM staging of ESC patients was determined according to the eighth edition of the TNM staging system by the American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) (6). Pathological diagnosis of ESC was reviewed independently by two pathologists with expertise in esophageal tumors, including histopathological slides and pathology reports.

Follow-up data were obtained through telephone interviews and outpatient visits. The study outcomes included overall survival (OS) and disease-free survival (DFS). OS was defined as the time from surgical treatment to death or the last follow-up date, while DFS was defined as the time from surgery to distant metastasis, local recurrence, or death from any cause.

The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Institutional Review Board (IRB) of the Cancer Hospital, Chinese Academy of Medical Sciences (No. 24/403-4683). The IRB waived the requirement for informed consent from patients because of the retrospective nature of this study.

Treatment methods

All 57 ESC patients in this study underwent radical surgical treatment, including 30 cases with the Sweet procedure, nine cases with the Ivor-Lewis procedure, and 18 cases with the McKeown procedure. Preoperative examination revealed no significant distant metastatic disease. Three patients received neoadjuvant therapy, including two cases of concurrent chemoradiotherapy and one case of concurrent chemoradiotherapy combined with targeted therapy. Forty-eight patients received surgery alone. Nine patients received postoperative adjuvant therapy, including four cases of concurrent chemoradiotherapy, three cases of adjuvant radiotherapy alone, and two cases of adjuvant chemotherapy alone.

Statistical analysis

Baseline characteristics of the cohort were analyzed using descriptive statistics or frequency analysis. Kaplan-Meier curves were used to assess OS and DFS of ESC patients. The Log-rank test was employed to compare survival differences between groups. Univariate and multivariate Cox regression analyses were conducted to evaluate the relationship between clinicopathological features and survival outcomes. All statistical analyses were performed using SPSS version 22.0 (IBM Inc., Chicago, IL, USA) and R version 4.4.0 (R Foundation, Vienna, Austria). A P value of <0.05 was considered statistically significant.

Results

Demographic information and tumor characteristics

This study included 57 patients with ESC who received treatment at the Cancer Hospital, Chinese Academy of Medical Sciences between January 2000 and December 2021. The screening process is illustrated in Figure 1. The baseline characteristics of all included patients are presented in Table 1. The mean age of ESC patients in this cohort was 59.07±8.24 years, with 48 (84.2%) male patients and 9 (15.8%) female patients, resulting in a male-to-female ratio of 5.3:1. A history of smoking was present in 38 (66.7%) patients, and 32 (56.1%) patients had a history of alcohol consumption. Additionally, 15 (26.32%) patients had other chronic diseases, including hypertension, diabetes, cerebral hemorrhage, cerebral infarction, and coronary heart disease.

Figure 1 Patient selection flowchart. ESC, esophageal sarcomatoid carcinoma.

In this study, 8 (14.0%) patients were preoperatively diagnosed with ESC through endoscopic biopsy. The most common primary site of ESC was the middle third of the esophagus (63.2%), followed by the lower third (29.8%), with only 7.0% of tumors occurring in the upper third of the esophagus. The average tumor diameter was 6.3 cm, with more than half of the patients having tumors larger than 5 cm. The intraluminal type was the most prevalent macroscopic pathological type, accounting for 54.4%.

Survival and recurrence

Follow-up information was available for all patients in this study, with a median follow-up time of 105.3 months (range, 98.5–112.1 months). As of January 1, 2024, 18 patients (31.6%) were still alive, and 39 patients (68.4%) had deceased. The median OS for the 57 patients was 38.2 months (Figure 2A), with 1-, 3-, and 5-year survival rates of 93.0%, 56.1%, and 37.5%, respectively. The median DFS was 28.9 months (Figure 2B), with 1-, 3-, and 5-year DFS rates of 87.8%, 43.2%, and 35.2%, respectively. Tumor size, lymph node status, and TNM stage correlated with OS and DFS (Figure 3). Patients with tumors ≤5 cm had longer OS than those with tumors >5 cm (P=0.02, Figure 3A). Lymph node-negative patients demonstrated significantly longer OS and DFS (P=0.001 and P=0.002, respectively; Figure 3B,3E). Similarly, patients with earlier TNM stages had longer OS and DFS (P=0.004 and P=0.009, respectively; Figure 3C,3F).

Figure 2 Overall survival and disease-free survival in the study cohort. (A) Overall survival. (B) Disease-free survival.

Figure 3 Kaplan-Meier survival curves. (A) Overall survival by Tumor size. (B) Overall survival by lymph node status. (C) Overall survival by TNM stage. (D) Disease-free survival by tumor size. (E) Disease-free survival by lymph node status. (F) Disease-free survival by TNM stage. The P value was calculated by log-rank test. LN, lymph node; TNM, tumor node metastasis.

Patterns of postoperative recurrence and metastasis in the ESC cohort are shown in Figure 4. Of the 57 patients, 38 (66.7%) experienced recurrence or metastasis postoperatively, with the highest incidence occurring in the second postoperative year (42.1%). Notably, 4 patients (10.5%) developed recurrence or metastasis more than 5 years after surgery (Figure 4A). Regional lymph nodes were the most common sites of recurrence, affecting 21 patients (55.3%) (Figure 4B).

Figure 4 Time to first recurrence or metastasis and site of recurrence or metastasis in the study cohort. (A) Time of the first recurrence and metastasis after surgery. (B) Number of cases of recurrence or metastatic sites.

Prognostic factor analysis

Further analyses assessed the relationship between each clinicopathologic factor and patient prognosis (Table 1). Univariate analysis revealed that tumor size, lymph node status, and TNM stage were significantly associated with prognosis. Patients with smaller tumors (median OS: ≤5 vs. >5 cm: 92.5 vs. 33.1 months; P=0.03), negative lymph node status (median OS and DFS: negative vs. positive: 91.6 vs. 28.7 months and 57.9 vs. 27.2 months; P<0.001 and P=0.004), and earlier TNM stages (median OS and DFS: stages I, II, III, IV: 92.5, 33.1, 28.7, and 18.5 months for OS; 57.9, 27.2, 13.9, and 4.0 months for DFS; P=0.01 and P=0.02) had significantly better outcomes.

Multivariate Cox regression analysis (Table 2) identified lymph node status as an independent prognostic factor for ESC. Negative lymph node status was significantly associated with prolonged OS and DFS (P=0.02 and P=0.01, respectively).

Discussion

This retrospective study highlights that ESC predominantly affects male patients, with the middle third of the esophagus being the most common site of occurrence. Preoperative pathological biopsy frequently fails to establish a definitive diagnosis due to the coexistence of carcinomatous and sarcomatous components within the tumor. Recurrence and metastasis predominantly manifest as lymph node involvement, most frequently occurring in the second postoperative year. The median OS and DFS in our cohort were 38.2 and 28.9 months, respectively, with 1-, 3-, and 5-year survival rates of 93.0%, 56.1%, and 37.5%. Notably, different surgical approaches and adjuvant therapies did not significantly impact OS or DFS.

A marked sex disparity was observed in this study, with male patients comprising a significantly larger proportion of cases, consistent with the sex distribution of EC in China (2). More than 50% of patients had a history of smoking or alcohol consumption, which are well-established risk factors for EC in China (7). Reports on tobacco and alcohol use in China indicate that these behaviors are more prevalent in men (8,9), which aligns with the higher incidence of EC in this population (10). Additionally, nearly all patients with a history of smoking or alcohol use in this cohort were male. Additionally, high BMI, another risk factor for EC (11), was present in 45.6% of patients in this cohort. These findings suggest that the epidemiological characteristics of ESC are similar to those of other common types of EC. Consistent with previous research on ESC and other types of EC (12,13), ESC in our cohort predominantly occurred in the middle third of the esophagus, followed by the lower third, possibly due to the presence of smooth muscle in these areas (13). ESC primarily exhibited intraluminal growth (14), as opposed to esophageal wall thickening, a pattern confirmed in our cohort.

Histologically, ESC consists of mixed carcinomatous and sarcomatous components, often dominated by sarcomatous elements (15,16). All cases in this study underwent preoperative biopsy, but diagnostic accuracy was low. Due to its rarity, ESC must be distinguished from pure sarcoma or SCC based on limited clinical experience. Kubo et al. recommend combining multi-site sampling with immunohistochemical staining for accurate histological diagnosis (17). Similarly, Shen et al. advocate integrating endoscopic features, microscopic examination, and immunohistochemistry for ESC diagnosis (18).

Postoperative recurrence or metastasis was most frequent in the second year, with regional lymph nodes being the most common sites, a finding consistent with previous studies (18). However, recurrence remains associated with poor prognosis, underscoring the aggressive nature of ESC. Compared to studies on the prognosis of esophageal SCC and esophageal AC (19,20), ESC appears to have a more favorable prognosis. This may be attributed to its pathological characteristics, as most ESCs exhibit polypoid intraluminal growth rather than deep invasion. Moreover, ESC-related symptoms often appear earlier in the disease course, facilitating timely diagnosis and treatment.

Given its rarity, no standardized treatment protocol has been established for ESC. In clinical practice, treatment strategies are often adapted from those for EC (15). Curative surgery, a standard treatment for EC (21), is also the primary choice for ESC (22). We propose that surgical approaches should be individualized based on tumor characteristics. In our cohort, over half of the patients underwent Sweet esophagectomy. While this approach may potentially compromise the completeness of upper mediastinal lymph node dissection, its correlation with postoperative nodal recurrence or metastasis remains debatable and requires further investigation. Hu et al. reported that different surgical approaches had no significant impact on ESC prognosis (15), a finding corroborated by our study. Limited by its low incidence, there has been little exploration of the efficacy of postoperative adjuvant therapies. Consistent with Hu et al. (15), our results showed that adjuvant therapy did not improve OS or DFS in ESC patients.

This study represents one of the largest cohort analyses of ESC, revealing its clinicopathological features and prognostic factors. However, several limitations should be acknowledged. First, the long study period introduces potential bias due to changes in diagnostic and therapeutic approaches over time. Second, the relatively good prognosis of ESC resulted in a limited number of cases receiving adjuvant therapy, restricting further exploration of treatment strategies. Third, as a retrospective study, the reliability of the data is inherently less robust compared to prospective studies. Nevertheless, given the rarity of ESC, prospective studies remain challenging. Large-scale, multicenter retrospective studies are needed to further elucidate the characteristics of ESC.

Conclusions

ESC is an exceptionally rare malignant esophageal tumor, with epidemiological characteristics seemingly similar to those of EC. However, treatment strategies modeled after EC appear to have limited effectiveness in improving ESC prognosis, highlighting the urgent need to develop specific therapeutic protocols for ESC. Early screening and improving biopsy accuracy may be effective approaches for enhancing survival and prognosis for ESC patients.

Acknowledgments

We thank all colleagues in our research group for their excellent discussions and technical assistance in this study.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1149/rc

Data Sharing Statement: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1149/dss

Peer Review File: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1149/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1149/coif). The 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 (IRB) of the Cancer Hospital, Chinese Academy of Medical Sciences (No. 24/403-4683). The IRB waived the requirement for informed consent from patients because of the retrospective nature of this 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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