Abstract
Background:
The lymphatic drainage of the esophagus primarily depends on the lymphatic vessels within the lamina propria mucosae and submucosa, which channel lymph longitudinally toward the proximal and distal ends. Our study sought to explore the prognostic significance of the lymph node metastasis station in patients with pathologic N+ esophageal squamous cell carcinoma (ESCC).
Materials and methods:
We retrospectively reviewed 544 patients who underwent esophagectomy alone for ESCC with pathologic lymph node metastasis between January 2012 and December 2016. The sites of lymph nodes were classified into zones according to the Japanese Classification of Esophageal Cancer. Univariate analysis and multivariable Cox regression model were applied to analyze disease-free survival (DFS) and overall survival (OS).
Results:
The metastasis rate of the middle paraesophageal lymph node (station 108) was 22.2%, which was significantly associated with advanced pathologic T stage (P < 0.001). Multivariable Cox regression analysis revealed that R0 resection, pT stage, pN stage, station 106recL, station 108 metastasis (hazard ratio, 1.485; P = 0.002), number of LN removed, and adjuvant therapy were independent prognostic factors for OS and pT stage, pN stage, station 106recR, station 108 metastasis (hazard ratio, 1.635; P < 0.001), number of LN removed, and adjuvant therapy for disease-free survival. Additional multivariate analysis showed that station 108 metastasis was an independent risk factor for locoregional recurrence-free survival (hazard ratio, 1.693; P = 0.001) and distant relapse-free survival (hazard ratio, 1.624; P = 0.001), together with pT stage, pN stage, number of LN removed, and adjuvant therapy.
Conclusions:
The high incidence in the station 108 metastasis was noted in patients with advanced pT stage ESCC. And the station 108 metastasis was associated with a worse prognosis in ESCC with lymph node involvement.
Graphical Abstracts
Keywords: ESCC, lymph node metastasis, station 108
Esophageal cancer is the sixth most common cause of malignancy-related death worldwide[1]. Approximately half of all cases are diagnosed in China, where esophageal squamous cell carcinoma (ESCC) constitutes over 90% of all cases[2]. The prognosis for patients undergoing esophagectomy alone remains poor, with a 5-year overall survival rate of 30%–40%[3,4].
HIGHLIGHTS
The metastasis rate of station 108 was significantly correlated with deeper infiltration depth of the tumor.
Station 108 was a relatively poor metastatic area and significantly associated with worse long-term survival and higher recurrence rate in esophageal squamous cell carcinoma with lymph node involvement.
Greater emphasis should be placed on improving the precision of preoperative evaluation and the administration of multidisciplinary treatment for patients with station 108 metastasis.
A survival benefit of multidisciplinary therapy has been demonstrated for patients with locally advanced esophageal cancer[4,5]. However, radical esophagectomy remains the cornerstone of curative treatment. Lymph node metastasis (LNM), a common and major metastatic pathway in esophageal cancer, is a critical prognostic factor for survival[6,7]. Due to the unique submucosal and intermuscular lymphatic drainage system of the esophagus, LNM in esophageal tumors is complicated and unpredictable[8,9]. Over the past decade, the impact of the number of resected lymph nodes on the survival of patients with esophageal cancer has been confirmed in many studies[10–12]. Furthermore, the increased number of metastatic lymph nodes has been incorporated into esophageal cancer staging since the seventh edition of the American Joint Committee on Cancer (AJCC)-TNM staging system. Esophagectomy with extensive lymph node dissection is generally recommended to enhance tumor staging accuracy and improve survival outcomes.
Previous studies have shown that dense lymphatic vessels in the lamina propria mucosae and submucosa of the esophagus primarily drain longitudinally toward the proximal and distal ends[13]. The lymphatic drainage of paraesophageal lymph nodes typically originates from intermuscular areas, with limited communication with submucosal lymphatics. As a result, metastasis to paraesophageal lymph nodes may correlate with the depth of tumor invasion. However, the association between the area of LNM and survival outcomes after esophagectomy remains scarcely investigated. Therefore, this study aimed to explore the association between the location of LNM and prognosis in patients with ESCC.
Patients and methods
This cohort study has been reported in line with the STROCSS guidelines[14].
Consecutive patients undergoing esophagectomy for primary esophageal cancer were identified from a prospectively maintained database between January 2012 and December 2016. The preoperative evaluation consisted of endoscopy, contrast-enhanced computed tomography (CECT) scan of the chest and upper abdomen, and upper gastrointestinal angiography. In total, 1528 patients were included. The following patients were excluded: patients diagnosed as non-squamous cell carcinoma histologically, patients without LNM, patients with neoadjuvant therapy, and patients without available outcome evaluations. Finally, 544 cases were enrolled in this study (Fig. 1).
Figure 1.
Study flowchart.
A transthoracic esophagectomy with routine two-field lymphadenectomy was performed. For patients with suspected cervical LNM on preoperative CECT, three-field lymphadenectomy was performed. All patients were recommended to undergo adjuvant therapy after surgery. Following multidisciplinary consultations, postoperative chemoradiotherapy or chemotherapy alone was tailored for patients based on their pathological characteristics. And adjuvant treatments were ultimately administered considering the patients’ recovery and preferences.
Patient characteristics were reviewed for age, gender, body mass index, history of smoking and alcohol, American Society of Anesthesiologists, surgical approach, and biological tumor features. Pathological results for all patients were recorded according to the eighth edition of the AJCC-TNM Classification[15]. The areas of LN were classified according to the LN map proposed by the Japanese Classification (Supplemental Digital Content Table 1, available at: http://links.lww.com/JS9/E297)[16]. Station 106pre, 106tbR, 106tbL, 107, 109 R, and 109 L were classified as hilar region in this study.
Post-surgery follow-up was performed every 3 months within the first year and after that every 6 months until death or for 5 years. After 5 years, the patients were assessed annually. Information on the first postoperative recurrence was used for this study. Overall survival (OS) was defined as the time from the date of surgery to the date of death from any cause or the last follow-up. Disease-free survival (DFS) was defined as the time from the date of R0 resection to the date of recurrence or death. Disease recurrence included locoregional recurrence (LRR) and distant recurrence (DR) in patients with R0 resection. LRR was defined as relapse within the esophagus or the mediastinum, the supraclavicular region, and the coeliac trunk lymph nodes. DR was defined as diffused disease in distant sites, including the cervical and (para-aortic) lymph node dissemination below the level of the pancreas, malignant pleural effusions, peritoneal carcinomatosis, and further hematogenous (organ) dissemination.
Statistical analysis
Continuous variables were described as the median with interquartile range (IQR), and categorical variables as the number of cases and percentages. A Mann–Whitney U test was carried out to identify the association between the rate of LNM and the infiltration depth of tumors. Survival was estimated by the Kaplan–Meier method. Multivariate Cox proportional hazards regression analysis with stepwise comparisons was used to assess the effect of different factors on survival. A two-sided P-value less than 0.05 was considered statistically significant, and hazard ratio (HR) and 95% confidence intervals (CIs) were expressed. Statistical analyses were performed with R (4.1.3) statistical software and SPSS of IBM Statistics (21.0).
Result
Patient demographics and tumor characteristics are shown in Table 1. A total of 544 cases were enrolled in the study, of which 458 (84.2%) were male and the median age was 62 (IQR, 56–67) years. Most tumors (n = 304, 55.9%) were located in the middle thoracic esophagus. An open surgical approach was performed in 372 patients (68.4%), and R0 resection was achieved in 505 patients (92.8%). A two-field lymphadenectomy was performed in 500 patients (91.9%) and the median number of total lymph node dissection was 16 (10–23). A total of 455 patients (83.6%) underwent adjuvant treatments.
Table 1.
Baseline characteristics of patients
| Variable | Median (IQR)/n (%) |
|---|---|
| Gender | |
| Male | 458 (84.2) |
| Female | 86 (15.8) |
| Age, yr | 62 (56–67) |
| BMI, kg/m2 | 22.69 (20.66–24.52) |
| ASA score | |
| 1 | 17 (3.1) |
| 2 | 436 (80.1) |
| 3 | 91 (16.7) |
| History of smoking | 257 (47.2) |
| History of drinking | 219 (40.3) |
| Tumor location | |
| Upper thorax | 76 (14.0) |
| Middle thorax | 304 (55.9) |
| Lower thorax | 164 (30.1) |
| Surgical approach | |
| Open | 372 (68.4) |
| MIE | 172 (31.6) |
| Lymphadenectomy | |
| Two-field | 500 (91.9) |
| Three-field | 44 (8.1) |
| Number of LND | 16 (10–23) |
| R0 resection | 505 (92.8) |
| pT stage | |
| 1 | 53 (9.7) |
| 2 | 84 (15.4) |
| 3 | 349 (64.2) |
| 4 | 58 (10.7) |
| pN stage | |
| 1 | 350 (64.3) |
| 2 | 163 (30.0) |
| 3 | 31 (5.7) |
| Histological grade | |
| Well | 37 (6.8) |
| Mod | 287 (52.8) |
| Poorly | 220 (40.4) |
| Tumor size, cm | 4 (3–5) |
| LVI | |
| Positive | 95 (17.5) |
| Negative | 449 (82.5) |
| Adjuvant therapy | |
| Yes | 455 (83.6) |
| No | 89 (16.4) |
ASA, American Society of Anesthesiologists; BMI, body mass index; IQR, interquartile range; LND, lymph node dissection; LVI, lymphatic venous invasion; MIE, minimally invasive esophagectomy.
Distribution of LNM
The yielded number per station and frequency of metastasis are summarized in Table 2. The metastasis rate of station 106recR and 108 was 27.4% and 22.2%, respectively. The metastasis rate of station 105, 106recR, and abdominal lymph node was significantly associated with tumor location. The correlation between LNM and the infiltration depth of tumors is shown in Table 3. The metastasis rate of station 108 was significantly correlated with deeper infiltration depth of the tumor, together with stations 105, 110, and hilar lymph node.
Table 2.
The correlation between rate of LNM and tumor location
| Lymph node stations | Number of LND | Metastatic rate | Upper | Middle | Lower | P-value |
|---|---|---|---|---|---|---|
| Median (IQR) | No. (%) | No. (%) | No. (%) | No. (%) | ||
| Upper paraoesophageal | 1 (0–2) | 65 (11.9) | 15 (19.7) | 40 (13.2) | 10 (6.1) | 0.006 |
| Right recurrent nerve | 2 (1–3) | 149 (27.4) | 41 (53.9) | 80 (26.3) | 28 (17.1) | <0.001 |
| Left recurrent nerve | 1 (0–2) | 70 (12.9) | 9 (11.8) | 40 (13.2) | 21 (12.8) | 0.954 |
| Hilar | 4 (2–6) | 95 (17.5) | 10 (13.2) | 59 (19.4) | 26 (15.9) | 0.355 |
| Middle paraoesophageal | 2 (1–2.5) | 121 (22.2) | 13 (17.1) | 78 (25.7) | 30 (18.3) | 0.096 |
| Lower paraoesophageal | 1 (0.5–2) | 114 (21.0) | 10 (13.2) | 61 (20.1) | 43 (26.2) | 0.058 |
| Abdominal | 5 (3–7) | 267 (49.1) | 21 (27.6) | 139 (45.7) | 107 (65.2) | <0.001 |
IQR, interquartile range; LNM, lymph node metastasis.
Table 3.
Correlation between the rate of LNM and the infiltration depth of tumors
| LN station | pT1 (%) | pT2 (%) | pT3 (%) | pT4 (%) | P-value |
|---|---|---|---|---|---|
| Upper paraoesophageal | 3.8 | 8.3 | 12.0 | 24.1 | 0.001 |
| Right recurrent nerve | 26.4 | 26.2 | 27.8 | 27.6 | 0.781 |
| Left recurrent nerve | 13.2 | 14.3 | 12.6 | 12.1 | 0.702 |
| Hilar | 7.5 | 9.5 | 18.6 | 31.0 | <0.001 |
| Middle paraoesophageal | 5.7 | 14.3 | 25.2 | 31.0 | <0.001 |
| Lower paraoesophageal | 13.2 | 10.7 | 23.8 | 25.9 | 0.005 |
| Abdominal | 43.4 | 51.2 | 50.7 | 41.4 | 0.781 |
LNM, lymph node metastasis.
Analysis of OS
The median follow-up for all censored patients was 30.6 months (IQR, 13.0–60.5). The 5-year OS rate was 33.1%, with a median OS of 31.2 months (Supplemental Digital Content Figure 1). The 5-year OS rate of patients with LNM was presented according to tumor location in Table 4. The lowest 5-year OS rate was noted in patients with station 108 LNM, which was 0%, 21.3%, and 3.5% in the upper, middle, and lower esophageal tumors, respectively. The patients with upper and middle esophageal tumors had a highest 5-year OS rate with 106recR LNM, which was 40.8% and 41.3%. The patients with lower esophageal tumors had a highest 5-year OS rate with station 110 LNM (30.4%).
Table 4.
The 5-year OS rate in patients with LNM according to tumor location
| Tumor location | Upper | Middle | Lower |
|---|---|---|---|
| LNM station | 5-year OS rate (%) | 5-year OS rate (%) | 5-year OS rate (%) |
| Upper paraoesophageal | 20.0 | 25.9 | 10.0 |
| Right recurrent nerve | 40.8 | 41.3 | 17.9 |
| Left recurrent nerve | 22.2 | 31.6 | 16.1 |
| Hilar | 20.0 | 28.8 | 20.2 |
| Middle paraoesophageal | 0 | 21.3 | 3.5 |
| Lower paraoesophageal | 24.0 | 21.5 | 30.4 |
| Abdominal | 9.5 | 31.5 | 25.5 |
LNM, lymph node metastasis.
Univariable analysis showed that surgical approach, R0 resection, pT stage, pN stage, tumor size, LVI, station 105 LNM, Hilar LNM, station 108 LNM, abdominal LNM, number of lymph node removed, and adjuvant therapy were significantly associated with OS (Table 5). In multivariable Cox regression analysis, station 108 LNM (HR, 1.485; 95% CI, 1.153–1.913; P = 0.002) was also identified as an independent prognostic factor for OS, along with R0 resection, pT stage and pN stage, left recurrent nerve LNM, number of lymph node removed, and adjuvant therapy (Table 5). The median and 5-year OS was 18.4 months and 14.7% for patients with station 108 LNM versus 38.1 months and 38.7 % for patients without station 108 metastasis (Fig. 2).
Table 5.
Univariable and multivariable Cox regression analyses of prognostic factors in patients with LNM
| Univariable analysis | Multivariable analysis | |||||||
|---|---|---|---|---|---|---|---|---|
| DFS | OS | DFS | OS | |||||
| Variable | HR (95% CI) | P-value | HR (95% CI) | P-value | HR (95% CI) | P-value | HR (95% CI) | P-value |
| Gender | 0.028 | 0.061 | ||||||
| Male | ||||||||
| Female | 0.689 (0.494–0.961) | 0.752 (0.558–1.013) | ||||||
| Age, yr | 1.013 (0.998–1.028) | 0.088 | 1.013 (0.999–1.027) | 0.080 | ||||
| BMI, kg/m2 | 1.024 (0.987–1.062) | 0.213 | 1.000 (0.966–1.036) | 0.988 | ||||
| ASA score | 0.708 | 0.804 | ||||||
| 1 | ||||||||
| 2 | 1.285 (0.672–2.455) | 0.941 (0.528–1.676) | ||||||
| 3 | 1.335 (0.675–2.642) | 1.027 (0.555–1.902) | ||||||
| History of smoking | 0.759 (0.585–0.985) | 0.038 | 0.925 (0.753–1.136) | 0.460 | ||||
| History of drinking | 1.189 (0.910–1.553) | 0.205 | 0.958 (0.777–1.181) | 0.685 | ||||
| Tumor location | 0.444 | 0.298 | ||||||
| Upper | ||||||||
| Middle | 0.811 (0.569–1.157) | 0.839 (0.620–1.137) | ||||||
| Lower | 0.951 (0.646–1.402) | 0.982 (0.710–1.136) | ||||||
| Surgical approach | 0.782 | 0.001 | ||||||
| Open | ||||||||
| MIE | 0.964 (0.742–1.252) | 0.678 (0.537–0.856) | ||||||
| Lymphadenectomy | 0.592 | 0.685 | ||||||
| Two-field | ||||||||
| Three-field | 1.111 (0.755–1.635) | 0.922 (0.623–1.365) | ||||||
| R0 surgery | / | 2.265 (1.581–3.245) | <0.001 | / | 1.857 (1.237–2.788) | 0.003 | ||
| pT stage | 0.002 | <0.001 | <0.001 | <0.001 | ||||
| 1 | ||||||||
| 2 | 1.027 (0.610–1.730) | 0.993 (0.606–1.628) | 0.936 (0.877–0.996) | 0.949 (0.900–1.000) | ||||
| 3 | 1.812 (1.150–2.857) | 1.920 (1.281–2.887) | 1.699 (1.446–1.992) | 1.708 (1.451–2.011) | ||||
| 4 | 2.216 (1.200–4.02) | 3.322 (2.060–5.357) | 2.207 (1.276–3.817) | 2.193 (1.316–3.649) | ||||
| pN stage | 0.022 | <0.001 | <0.001 | <0.001 | ||||
| 1 | ||||||||
| 2 | 1.500 (1.125–2.001) | 1.769 (1.418–2.207) | 1.772 (1.768–1.774) | 1.747 (1.738–1.752) | ||||
| 3 | 1.471 (0.793–2.729) | 3.031 (2.036–4.512) | 2.128 (1.339–3.378) | 2.667 (1.689–4.201) | ||||
| Histological grade | 0.189 | 0.860 | ||||||
| Well | ||||||||
| Mod | 0.972 (0.629–1.502) | 1.030 (0.679–1.562) | ||||||
| Poorly | 0.790 (0.505–1.235) | 0.970 (0.634–1.482) | ||||||
| Tumor size, cm | 1.014 (0.941–1.091) | 0.722 | 1.118 (1.053–1.187) | <0.001 | ||||
| LVI | 1.243 (0.933–1.655) | 0.137 | 1.434 (1.112–1.849) | 0.005 | ||||
| LNM | ||||||||
| Upper paraoesophageal | 1.209 (0.863–1.693) | 0.270 | 1.348 (0.999–1.817) | 0.050 | ||||
| Right recurrent nerve | 0.823 (0.621–1.091) | 0.175 | 0.881 (0.697–1.113) | 0.288 | 0.772 (0.598–0.996) | 0.047 | ||
| Left recurrent nerve | 1.349 (0.957–1.900) | 0.087 | 1.322 (0.983–1.778) | 0.065 | 1.430 (1.019–2.010) | 0.039 | ||
| Hilar | 0.965 (0.707–1.316) | 0.821 | 1.311 (1.013–1.697) | 0.040 | ||||
| Middle paraoesophageal | 1.810 (1.367–2.396) | <0.001 | 1.952 (1.553–2.453) | <0.001 | 1.635 (1.262–2.118) | <0.001 | 1.485 (1.153–1.913) | 0.002 |
| Lower paraoesophageal | 1.158 (0.879–1.527) | 0.297 | 1.225 (0.982–1.603) | 0.069 | ||||
| Abdominal | 1.024 (0.987–1.062) | 0.241 | 1.305 (1.063–1.603) | 0.011 | ||||
| Number of LND | 0.992 (0.977–1.007) | 0.309 | 0.982 (0.967–0.996) | 0.015 | 0.988 (0.972–0.999) | 0.049 | 0.970 (0.956–0.985) | <0.001 |
| Adjuvant therapy | 0.724 (0.574–0.913) | 0.006 | 0.648 (0.518–0.811) | <0.001 | 0.659 (0.521–0.832) | <0.001 | 0.576 (0.460–0.722) | <0.001 |
ASA, American Society of Anesthesiologists; BMI, body mass index; CI, confidence interval; DFS, disease-free survival; HR, hazard ratio; LND, lymph node dissection; LNM, lymph node metastasis; LVI, lymphatic venous invasion; MIE, minimally invasive oesophagectomy; OS, overall survival.
Figure 2.
Kaplan–Meier curves for patients with or without station 108 metastasis (A) disease-free survival; (B) overall survival.
Analysis of DFS
Of 505 R0 resections, 275 (54.5%) had recurrent disease. The 5-year DFS rate was 30.6%, with a median DFS of 23.8 months (Supplemental Digital Content Figure 1). In univariable analysis, gender, history of smoking, pT stage, pN stage, station 108 LNM, and adjuvant therapy were significantly associated with DFS (Table 5). In multivariable Cox regression analysis, station 108 LNM (HR, 1.635; 95% CI, 1.262–2.118, P < 0.001) was significantly associated with DFS, together with pT stage, pN stage, right recurrent nerve LNM, number of lymph node removed, and adjuvant therapy (Table 5). The median and 5-year DFS was 11.0 months and 12.6% for patients with station 108 metastasis versus 28.5 months and 35.7% for patients without station 108 metastasis (Fig. 2).
A total of 155 (30.7%) patients experienced LRR and 199 (39.4%) patients experienced distant relapse. Additional multivariate Cox regression analysis showed that station 108 LNM was an independent factor for LRR-free survival (HR, 1.693; 95% CI, 1.235–2.322; P = 0.001) and DR-free survival (HR, 1.624; 95% CI, 1.208–2.182; P = 0.001), together with pT stage, pN stage, number of lymph node removed, and adjuvant therapy Supplemental Digital Content Table 2, available at: http://links.lww.com/JS9/E297).
Discussion
The presence of LNM is one of the most critical adverse factors for prognosis in esophageal cancer. In this study, we observed that station 106recR and station 108 were the most frequent sites of mediastinal LNM. The metastasis rates of station 105, 106recR, and abdominal lymph nodes were significantly associated with the tumor location, while the incidence of paraesophageal LNM (station 105, 108, and 110) increased with deeper infiltration depth of the tumor. Furthermore, multivariable analysis identified station 108 metastasis as an independent prognostic factor for worse OS and DFS.
Numerous studies have examined the association between the extent of lymph node dissection and prognosis[10–12,17]. Systemic lymphadenectomy has been widely endorsed for achieving more accurate tumor staging and improved loco-regional disease control. And the resection of >15 LNs is currently recommended by the NCCN guideline for patients receiving surgery alone. While the eighth edition of the esophageal TNM staging system incorporates the number of involved nodes, it does not account for the location of LNM. The distribution of LNM varies based on tumor histology, location, and invasion depth. And the prognostic significance of the area of LNM in patients with esophageal cancer remains insufficiently investigated.
Anderegg et al[18] concluded that both the number and location of LNM are independent predictors of survival in patients with esophageal or gastroesophageal junction adenocarcinoma. In their study, all patients received transthoracic esophagectomy with two-field lymphadenectomy following neoadjuvant therapy and LNM along the celiac axis and/or the proximal field had a negative impact on prognosis. Tachimori and colleagues evaluated the efficacy of lymph node dissection by area according to the location of the primary tumor and used the efficacy index to calculate the survival benefit of lymphadenectomy[19]. They determined that the efficacy index of each node zone differed by tumor location and recommended that the area of dissection be modified according to the tumor location. Miyata and colleagues demonstrated that metastasis of the celiac LN and middle mediastinal LN is independent prognostic factor for patients with middle and lower thoracic esophageal cancer who underwent neoadjuvant chemotherapy followed by surgery[20]. Moreover, they observed a high efficacy index for paraesophageal LNs.
Previous anatomical study has verified the presence of abundant lymphatic vessels draining longitudinally within the mucosae and submucosa of the esophagus[8,13]. These longitudinal lymphatic channels extend to the proximal esophagus and cardia. And a morphological connection between submucosal lymphatic vessels and recurrent nerve nodes in the superior mediastinum was observed by Mizutani et al[21]. Consistent with these findings, our study observed frequent metastases to LNs along the recurrent nerve and celiac axis in patients with tumors confined to the mucosae and submucosa layer. Additionally, no notable differences in the metastasis rate of these areas were observed among patients with varying infiltration depths of tumors. These results align with the characteristic of esophageal lymphatic drainage and may partially explain the high incidence of skip metastases in ESCC.
Furthermore, lymphatic channels to paraesophageal lymph nodes usually originate from the intermuscular area with limited communication with lymphatic drainage in the submucosa[13]. Consistent with this histological finding, the metastasis rate of paraesophageal lymph nodes was low in patients with tumors confined to the mucosae and submucosa layer. However, the metastasis rate increased in patients with greater infiltration depth of tumors. The metastasis of paraesophageal lymph nodes might be a sign of advanced disease. In the current study, multivariable analysis identified station 108 metastasis as an independent prognostic predictor of worse OS and DFS, along with the pT stage, pN stage, number of lymph node removed, and adjuvant therapy. Additionally, station 108 metastasis remained an independent prognostic predictor for both LRR-free survival and DR-free survival.
Adjuvant therapy is crucial for improving the prognosis of advanced esophageal cancer[22,23]. Our study confirmed it as an independent prognostic factor for both OS and DFS in multivariable Cox regression analyses. These results emphasize the importance of adjuvant therapy in mitigating recurrence risk and improving survival outcomes, thereby underscoring the pivotal role of multidisciplinary treatment in patients undergoing curative resection for advanced esophageal cancer. Additionally, immune checkpoint inhibitors have emerged as a promising treatment for advanced esophageal cancer in recent years[24–26]. Immunotherapy holds potential to further improve the prognosis of ESCC patients with station 108 metastasis.
The present study had several limitations. First, it was a retrospective study conducted in a single institution, which might lead to a potential selection bias. Second, our study focused on patients with squamous cell carcinoma, reflecting the predominant histological type in Asia[27]. Although neoadjuvant chemoradiotherapy has been regarded as the standard of care for patients with locally advanced esophageal cancer[4,5], this study included only patients who received surgery alone to avoid the confounding effects of neoadjuvant therapy on lymphatic drainage. Further validation in larger, multicenter studies is needed to generalize these results to a broader esophageal cancer population.
In conclusion, our study indicated that station 108 was a relatively poor metastatic area, and the high incidence in station 108 metastasis was noted in patients with advanced pT stage ESCC. And the station 108 metastasis was significantly associated with worse long-term survival and higher recurrence rate in patients with lymph node involvement. More attention should be paid to enhance precision in preoperative evaluation and the administration of multidisciplinary treatment for patients with suspected station 108 metastasis.
Written informed consent was obtained from the patient for publication of this study. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request.
Any datasets generated during and/or analyzed during the current study are available upon reasonable request.
Acknowledgments
The authors thank Professor Ge Di and Professor Ma Teng for their valuable discussions and insights.
Footnotes
H.J. and Y.S. contributed equally to this work.
Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.
Supplemental Digital Content is available for this article. Direct URL citations are provided in the HTML and PDF versions of this article on the journal's website, www.lww.com/international-journal-of-surgery.
Published online 5 June 2025
Contributor Information
Haoyao Jiang, Email: starsjo123@163.com.
Yifeng Sun, Email: suychest@126.com.
Rong Hua, Email: askyou999@126.com.
Xufeng Guo, Email: jojoch111@yeah.net.
Ethical approval
The ethics committee approved this study of Shanghai Chest Hospital [ID: IS23059].
Consent
Written informed consent was obtained from the patient for publication of this study. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request.
Sources of funding
The study was funded by grants from the Shanghai Science and Technology Development Foundation 20Y11909200 and the Shanghai Esophageal Cancer Database SHDC2020CR6002.
Author contributions
Conceptualization; data curation; formal analysis; writing – original draft: H.J.; investigation; methodology; writing – original draft: Y.S.; methodology; resources: R.H.; supervision; visualization: X.G.; conceptualization; investigation; resources: B.L.; investigation; software: Y.H.; resources: H.G.; supervision; writing – review and editing: Z.L.
Conflicts of interest disclosure
Not applicable.
Research registration unique identifying number (UIN)
PROSPERO 2025:CRD420251021238. Available from https://www.crd.york.ac.uk/PROSPERO/view/CRD420251021238.
Guarantor
Dr. Zhigang Li.
Provenance and peer review
Not applicable.
Data availability statement
Any datasets generated during and/or analyzed during the current study are available upon reasonable request.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
Any datasets generated during and/or analyzed during the current study are available upon reasonable request.