Clinical characteristics and survival of esophageal cancer patients: annual report of the surgical treatment in Shanghai Chest Hospital, 2017

Introduction

Esophageal cancer is the seventh most frequently diagnosed cancer and the sixth leading cause of cancer-related deaths in the world (1). China has the highest number of incident cases at the national level (2). As a high-volume center of esophageal cancer in China, the third annual report for Shanghai Chest Hospital (SCH) is summarized here. Baseline characteristics, diagnosis, tumor related information, treatment relevant information, perioperative outcomes, pathology results, and survival information of patients are described in this report.

After the learning curve of the first 2 years, robotic-assisted esophagectomies (RAE) gradually show better surgical efficiency and lymph node dissection capabilities and have been carried out in large numbers in SCH since 2017. To reduce the incidence of anastomotic leakage, the route of conduit pull-up gradually shifts from the retrosternal to the posterior mediastinum. In 2017, preoperative neoadjuvant treatment still had not been recommended in our clinical practice like in Japan. But in the subgroups of different stages in the same period, there was no obvious survival disadvantage compared with the Japanese annual report (3). The beneficiaries of neoadjuvant therapy were still not clear in 2017 at SCH. At that time, immunotherapy was not yet available in neoadjuvant regimen. We present this article in accordance with the STROBE reporting checklist (available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-49/rc).

Methods

Data sources

To record patients’ related information, a prospective database of esophageal cancer has been established in 2014. The following patients’ information was recorded: baseline characteristics, diagnosis, tumor related information, treatment relevant information perioperative outcomes, pathology results and survival information. For treatment relevant information, postoperative complications were classified by Esophagectomy Complications Consensus Group (ECCG) system and Clavien-Dindo (C-D) grading system (4,5). For residual tumor status, residual tumor was examined at proximal, distal and circumferential margins of the resected esophageal specimen. R0 was defined as negative resection margins; R1 was defined as positive residual tumor in resected esophagus; and R2 was defined as unresectable tumor which invaded adjacent organs. For survival information, follow-up was scheduled every 3 months during the first year after discharge from the SCH, and then every 6 months in the following years until June 2023. Finally, overall survival (OS), cancer-specific survival (CSS) and recurrent free survival (RFS) were calculated.

Clinical data

Clinical data of patients who received surgical treatments (esophagectomy or endoscopic resection) for esophageal cancer in 2017 were retrieved from the esophageal cancer disease database of SCH. Finally, a total of 663 patients who received esophagectomy or endoscopic submucosal dissection (ESD) for esophageal cancer at SCH in 2017 were included, three of them who received esophagectomy the same year after ESD were only included in ESD cohort. To compare the patients’ survival between 2016 and 2017, the cohort of 2016 at SCH was also included (6). According to clinical records, baseline characteristics were analyzed in all 663 patients (Table 1). For analysis of long-term survival after esophagectomy, the 610 patients who received esophagectomy were reviewed except for 18 patients who were lost to follow-up in the first year after surgery (Figure 1). The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013) (7). The study was approved by the ethics committee of the Shanghai Chest Hospital (No. KS23067). Individual consent for this retrospective analysis was waived.

Figure 1 Flowchart of this report. ESD, endoscopic submucosal dissection.

Diagnosis and evaluation

The diagnosis of patients was confirmed by esophagogastroduodenoscopy (EGD) for location and biopsy of the lesion. Contrast-enhanced computed tomography (CT) scan of esophagus (including neck, chest and abdomen) was routinely used for tumor and metastatic lymph node staging. For intramucosal invasion, endoscopic ultrasonography (EUS) was used for further tumor staging. For cervical esophageal cancer patients, neck ultrasound was used for supraclavicular lymph node staging (lymph nodes between the supraclavicular paratracheal space and apex of the lung). For suspected distant metastases, additional enhanced magnetic resonance imaging (MRI) for brain or bone radionuclide scans were performed. The staging was based on the 8^th edition of the American Joint Committee on Cancer (AJCC) tumor-node-metastasis (TNM) staging criteria for esophageal cancer (8).

To assess patients’ general condition, evaluation of cardiopulmonary function was conducted, such as echocardiography, treadmill test, pulmonary function, and arterial blood gas. Additionally, nutritional assessment was mandatory for admission.

Esophagectomy or endoscopic resection

McKeown and Ivor-Lewis approaches through right thoracic approach were common options for esophagectomy at SCH in 2017. Minimally invasive esophagectomy (thoracoscopic or robotic-assisted) were the mainstream in our center, but some cases of open approach were still performed depending on the decision of surgeons, most for the suspected adjacent organ invaded (T4b) cases. Considering the reduced surgical tolerance in certain patients, these individuals underwent Sweet procedure with a left thoracic approach or trans-hiatal approach (Table 2). For lymphadenectomy, extended two-field or selective three-field lymph node dissection was routinely performed (Table 3).

Endoscopic resection was used in patients diagnosed with clinical intramucosal invasion accompanied by negative lymph node metastases (cT1N0) confirmed by contrast-enhanced computed tomography (CT) and EUS. For patients who underwent circumferential resection, esophageal stent may be implanted simultaneously to avoid stenosis after operation. For postoperative confirmed staged pT1b or residual tumors, additional esophagectomy or definitive radiotherapy was considered.

Multidisciplinary treatment

Multidisciplinary treatment was mainly used in patients with advanced tumors. In 2017, neoadjuvant therapy had not been routinely applied for preoperative treatment, but was mainly used for suspected lymph node metastasis or adjacent tissue invade (T3 to T4a) (Table 4). And the specific treatment regimen varied depending on the physician and patients’ preference (Table 5). For patients with a tumor located in the upper thoracic esophagus or neck or confirmed with lymph node metastases after postoperative pathology, postoperative adjuvant therapy was routinely recommended.

Statistical analysis

For this report, categorical variables were documented as numbers and percentages. Continuous variables were documented as mean ± standard deviation (SD) for normal distribution data or median [interquartile range (IQR)] for non-normal distribution data. Survival data were graphed and analyzed by Kaplan-Meier method and compared by log-rank test. Multivariate Cox regression analysis was conducted to explore prognostic factors affecting long-term outcome. To explore the probable survival benefits of neoadjuvant therapy, propensity score match (PSM) was used in ESCC patients. A two-tailed test P value less than 0.05 two-sided was considered statistically significant. All analyses were performed by SPSS software version 25.0 (IBM Corporation, Armonk, NY, USA) and were plotted by GraphPad Prism 9 software (GraphPad Software, San Diego, CA, USA).

Results

Baseline characteristics

A total of 663 patients received surgical treatment at SCH in 2017 (Figure 1). The majority of patients were male (83.1%), with 49.3% of patients aging 60–69 years. In 54 (8.1%) patients, their body mass index (BMI) were less than 18.5 kg/m² which was considered as malnourished. The tumor was mainly located at the middle thoracic esophagus (55.2%) and initially diagnosed as esophageal cancer (98.2%) (Table 1).

Resection

Of the 663 patients who received tumor resection, 628 (94.7%) received esophagectomy and 35 (5.3%) received ESD (Table 2). Due to unsatisfactory results of endoscopic resection, three cases received additional surgery in the same year (Figure 1).

Esophagectomy

Of all the esophagectomy approaches (n=628), McKeown approach accounted for the majority (76.6%), followed by Ivor-Lewis (6.6%), Sweet (6.3%), trans-hiatal (2.6%), total pharyngo-laryngo-esophagectomy (TPLE) (1.1%), and so on (Table 2). Minimally invasive techniques were used in 70.7% of patients (n=444), including RAE in 130 patients (20.7%) (Table 3). Complete resection (R0) was achieved in 90.3% of patients (Table 6). The gastric tube was used in 97.8% of patients for conduit, and the posterior mediastinum was the most commonly chosen route (Table 3). For lymph node dissection, two fields (thoracic + abdominal) dissection was performed in 540 (86%) patients, which accounted for the majority (Table 3). A total of 622 patients underwent lymph node dissection, with a median of 17 lymph nodes examined (Table 7), meeting the National Comprehensive Cancer Network (NCCN) guidelines (9).

Endoscopic submucosal dissection

In the 35 patients diagnosed with clinical intramucosal invasion accompanied with no lymph node metastases, ESD was performed. No severe complications after ESD were recorded. Eight patients received adjuvant therapy after resection and salvage esophagectomies were performed in three patients (Table 4).

Pathological evaluation

In pathological evaluation, esophageal squamous cell carcinoma (ESCC) was the most prevalent type at SCH, accounting for 587 out of 663 patients (Tables 8,9), prominent for moderate to poor differentiation (86.1%) (Table 10). The pathological depth of tumor invasion was most commonly pT3 (invasion of the adventitia) in esophagectomy cases, representing 317 cases (50.5%) (Table 11). Lymph node metastases were observed in 329 patients (52.4%), comprising 181 cases staged as pN1 (28.8%) and 107 cases staged as pN2 (17.0%) (Table 12). Notably, 251 cases (40.0%) were categorized as pStage III and 78 cases (12.4%) were categorized as pStage IV after esophagectomy (Table 13). 117 patients (18.7%) exhibited no lymphovascular invasion (Table 12).

Regarding the ESD specimens, the pathological depth of tumor invasion was dominated by pStage T1a-M3 (invade the muscularis mucosa) in ESD cases, accounting for 12 (34.3%) cases (Table 14). Unfortunately, the depth of tumor invasion of three cases failed to be defined (one in pT1a and two in pT1b).

Multidisciplinary treatment

Perioperative multidisciplinary treatment was performed in the 355 esophagectomy patients and eight ESD patients. Of the patients who received perioperative treatment, 37 patients received preoperative therapy before esophagectomy without postoperative therapy, 286 patients received postoperative therapy without preoperative therapy, and 32 patients received both. Eight patients received postoperative adjuvant therapy after ESD (Table 4). The preoperative neoadjuvant regimens are summarized in Table 5.

Complications

Following esophagectomy, our patients were routinely admitted to the ICU to prevent postoperative emergencies. As a result, the median length of ICU stay is two days (Table 7). A total of 309 (49.2%) patients who received esophagectomy experienced postoperative complications, with major complications (C-D ≥ III) documented in 87 patients. In 2017, recurrent laryngeal nerve injury emerged as the most common complication at SCH, with a prevalence of 14.2%, followed by postoperative pneumonia at 13.2%. Other notable complications included pleural effusion (8.9%), anastomotic leakage (8.9%), and acute respiratory distress syndrome (ARDS) (4.6%) (Table 15). The postoperative mortality was 0.008% (5 cases) for 30-day and 0.021% (14 cases) for 90-day.

Survival analysis

Most patients were followed up until June 2023. The median follow-up time was 60.2 (IQR, 36.33–60.87) months in the ESD cohort and 60.87 (IQR, 60.4–60.93) months in the esophagectomy cohort. Eighteen patients with follow-up of less than 1 year were excluded from the survival analysis (Figure 1). Overall, the 1-, 2-, 3-, 4-, and 5-year OS rates were 83.5%, 68.6%, 60.4%, 56.5%, and 52.9% (Figure 2). Notably, there were no statistically significant differences between the survival outcomes among patients with different histology of esophageal cancer (Figure 3). Furthermore, patients with ESCC who underwent esophagectomy at SCH in 2016 and 2017 exhibited similar survival trend (Figure 4). Although the 5-year OS of 2017 cohort is slightly higher than that of 2016 cohort (52.5% vs. 51.8%), 1-year OS presents opposite results (83.2% vs. 86.5%). Subgroup analyses were conducted by clinical stage (cStage), pathological stage (pTNM, pT, pN) and residual tumor (R) in patients with ESCC (Figures 5-10). To explore the probable survival benefits of neoadjuvant therapy, 68 pairs of ESCC patients with neoadjuvant treatment or not were analyzed through PSM (Figure 11, Table S1). Kaplan-Meier survival curves were plotted for them to evaluate their efficacy. However, there were no substantial differences in survival between the two cohorts.

Figure 2 The survival of overall cohort. OS, overall survival; CSS, cancer specific survival.

Figure 3 The survival of patients who received esophagectomy with different histological pathology. (A) The OS of patients who received esophagectomy with different histological pathology; (B) the CSS of patients who received esophagectomy with different histological pathology. OS, overall survival; CSS, cancer specific survival; ESCC, esophageal squamous cell carcinoma; AC, adenocarcinoma.

Figure 4 The survival of ESCC patients who received esophagectomy in 2016 and 2017. (A) The OS of ESCC patients who received esophagectomy in 2016 and 2017; (B) the CSS of ESCC patients who received esophagectomy in 2016 and 2017. OS, overall survival; CSS, cancer specific survival; ESCC, esophageal squamous cell carcinoma.

Figure 5 The survival of ESCC patients who received esophagectomy with different clinical stage (AJCC 8^th edition). (A) The OS of ESCC patients who received esophagectomy with different clinical stage (AJCC 8^th edition); (B) the CSS of ESCC patients who received esophagectomy with different clinical stage (AJCC 8^th edition). OS, overall survival; CSS, cancer specific survival; ESCC, esophageal squamous cell carcinoma; AJCC, American Joint Committee on Cancer.

Figure 6 The survival of ESCC patients who underwent esophagectomy according to pathological stage (AJCC 8^th edition). (A) The OS of ESCC patients who underwent esophagectomy according to pathological stage (AJCC 8^th edition); (B) the CSS of ESCC patients who underwent esophagectomy according to pathological stage (AJCC 8^th edition). OS, overall survival; CSS, cancer specific survival; ESCC, esophageal squamous cell carcinoma; AJCC, American Joint Committee on Cancer.

Figure 7 The survival of ESCC patients who underwent esophagectomy according to pathological and neoadjuvant stage (AJCC 8^th edition). (A) The OS of ESCC patients who underwent esophagectomy according to pathological and neoadjuvant stage (AJCC 8^th edition); (B) the CSS of ESCC patients who underwent esophagectomy according to pathological and neoadjuvant stage (AJCC 8^th edition). OS, overall survival; CSS, cancer specific survival; ESCC, esophageal squamous cell carcinoma; AJCC, American Joint Committee on Cancer.

Figure 8 The survival of ESCC patients who received esophagectomy with different depth of tumor invasion (AJCC 8^th edition). (A) The OS of ESCC patients who received esophagectomy with different depth of tumor invasion (AJCC 8^th edition); (B) the CSS of ESCC patients who received esophagectomy with different depth of tumor invasion (AJCC 8^th edition). OS, overall survival; CSS, cancer specific survival; ESCC, esophageal squamous cell carcinoma; AJCC, American Joint Committee on Cancer.

Figure 9 The survival of ESCC patients who received esophagectomy with different lymph node metastasis (AJCC 8^th edition). (A) The OS of ESCC patients who received esophagectomy with different lymph node metastasis (AJCC 8^th edition); (B) the CSS of ESCC patients who received esophagectomy with different lymph node metastasis (AJCC 8^th edition). OS, overall survival; CSS, cancer specific survival; ESCC, esophageal squamous cell carcinoma; AJCC, American Joint Committee on Cancer.

Figure 10 The survival of ESCC patients with different postoperative residual tumor status (AJCC 8^th edition). (A) The OS of ESCC patients with different postoperative residual tumor status (AJCC 8^th edition); (B) the CSS of ESCC patients with different postoperative residual tumor status (AJCC 8^th edition). OS, overall survival; CSS, cancer specific survival; ESCC, esophageal squamous-cell carcinoma; AJCC, American Joint Committee on Cancer.

Figure 11 The survival of neoadjuvant therapy in ESCC patients (propensity score matching, n=55). (A) The OS of neoadjuvant therapy in ESCC patients (propensity score matching, n=55); (B) the CSS of neoadjuvant therapy in ESCC patients (propensity score matching, n=55). OS, overall survival; CSS, cancer specific survival; NAT, neoadjuvant therapy; ESCC, esophageal squamous-cell carcinoma.

In multivariate Cox regression analysis, open surgery approach, deeper tumor invasion layers, and more lymph nodes metastasis were prognostic factors associated with poor OS, CSS and RFS in esophagectomy cohort. Postoperative adjuvant treatment was factor associated with better OS (Table 16).

Discussion

This is a report of esophageal cancer from a high-volume center in China. With more than 600 esophagectomies every year are of huge workload. Our surgeries come from eight surgeons, and most of them had performed more than 400 surgeries. The remaining five are senior fellows, who can complete the surgery independently or with the assistance of supervisor. The quality of esophagectomy can be fully guaranteed.

EUS is recommended by many guidelines as an important tool for T or N staging of esophageal cancer (1,10). However, in the 2017 cohort of SCH, it was still only used for rough screening of superficial lesions. For advanced tumors, the main concerning point was whether the adjacent organs were invaded (staging T4b), and the most important tool for judging this was still CT scan. Although MRI was recommended for possible adjacent organ invasion (T4b), and PET scan was recommended for staging, they were still not commonly used. This principle was also presented in Japan’s JCOG1510 study (11). Therefore, we insisted not to use EUS as a T staging tool for advanced esophageal cancer. Superficial lesions were mainly distinguished between T1a and T1b, because it seems that these two types have to be treated separately in recent years, but JCOG0508 has presented that low-risk T1b patients can also choose non-surgical treatment (12). The depth of the invasion has become the most important basis for surgery. However, correct staging by EUS is critical (13).

Minimally invasive surgery became the preferred approach at SCH in 2017. Of the different surgical approaches, patients who received RAE showed the best survival (Figure S1). However, this result may be influenced by patient selection and therefore unreliable. Open surgeries were more commonly used for patients with T4b tumor. Most of open surgeries were through the left chest because it is easier to remove esophageal cancer with aorta invasion, and any necessary combined aortic resection can be performed at the same time. Combined tracheal resection was used in attempt to treat esophageal cancer with airway invasion, but the results were not ideal (Table 17). The postoperative 5-year OS of patients staged pT4b was only 14.7%.

Multidisciplinary treatment in 2017 was still mainly postoperative adjuvant treatment. There are many reasons for this. The CROSS regimen (carboplatin + paclitaxel + radiotherapy) was not included in the NCCN guidelines until 2019 (9,14), and China’s 5010 research had not been officially announced until 2018 (15). Another important reason is that most of our patients came from other cities, and the cost of continuous preoperative treatment in Shanghai was too high to afford. They preferred to receive surgery first and then returned to the local area for any additional treatment. Thus, the beneficiaries of neoadjuvant therapy were still unclear in 2017 cohort.

In the past medical record of SCH, the safety of surgery is relatively acceptable. The 30-day surgical mortality rate of the entire group in 2017 was only 0.008%. With the emphasis on mediastinal lymph node dissection and the advantages of RAE, surgeons have more confidence to perform radical lymph node dissection and expose the recurrent laryngeal nerve. Thus, the incidence of recurrent laryngeal nerve injury had increased significantly, which is difficult to see and difficult to accept in West. However, according to recent research in Asia, most recurrent laryngeal nerve injuries are temporary and can recover within 6 months, with no impact on long-term survival (16,17). In the future, the prevention of recurrent laryngeal nerve injury may prove to be essential for optimizing patient outcomes and enhancing overall quality of life.

We recognize that our study has limitations. This is a very typical Asian esophageal cancer cohort, with mainly squamous cell carcinoma. Perhaps our clinical staging is still not accurate enough, and there was not enough analysis of specific causes of death during follow-up, especially non-tumor causes of death and the occurrence of second tumors. In addition, non-surgical patients who received internal medical treatment alone were not included in the analysis.

Conclusions

The focus of this report is to describe the long-term survival after surgical treatment of esophageal cancer in a single center in China. Our 5-year OS is 52.9%, which is lower than Japan’s 2015 results (59.9%) (3). But we should notice that 40.7% of patients in the Japanese annual report of 2015 were staged T1, which only accounted for 17.7% in our cohort. In subgroup analysis, especially among stage II–III patients, our survival results were comparable to those in Japan. Therefore, advanced tumor stage may be the main reason for the above differences in OS. We cannot compare these groups directly because of factors such as induction treatment, staging and so on. We hope this report would provide reference for diagnosing and treatment of esophageal cancer in the future.

Acknowledgments

Funding: This work was supported by the Shanghai Municipal Education Commission-Gaofeng Clinical Medicine (No. 20181816).

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-49/rc

Data Sharing Statement: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-49/dss

Peer Review File: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-49/prf

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-49/coif). L.Z.G serves as Associate Editor-in-Chief of Journal of Thoracic Disease from April 2024 to April 2025. 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 (as revised in 2013). The study was approved by the ethics committee of the Shanghai Chest Hospital (No. KS23067). Individual consent for this retrospective analysis was waived.

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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