Retrospective Analyses of the Clinicopathological and Prognostic Features of Esophageal Squamous Cell Carcinoma in a Grade A Tertiary Hospital in Xinjiang, China

Background: The aim of this invesigation was to retrospectively analyze and summarize the clinicopathological and prognostic features of patients with esophageal squamous cell carcinoma (ESCC) at the Cancer Hospital Aliated of the Xinjiang Medical University , a Grade A tertiary hospital in Xinjiang. Methods: The clinicopathological data and follow-up data were collected from 419 ESCC patients . The overall survival (OS) and the related factors affecting survival were analyzed. Results: Among the patients , 265 (63.2%) did not receive any postoperative treatment. The 1-, 3-, and 5-year overall survival (OS) rates were 84.8%, 47.5%, and 37.3%, respectively, and the median survival time (MST) was 29.0 months . Multivariate analysis showed that sources of patients, tumor stage, lymph node metastasis and stage of the disease were the independent predictors of OS. The nding in subgroup analysis indicated that there was a positive relationship between area and overall survival. Conclusions: Postoperative treatments of these patients with ESCC were shown to be inadequent. Postadjuvant therapies of patients need to be strengthened. Targeted treatment regimes of different regions should be carried out by health department to alleviate the cancer burden.

Currently, the main treatments for ESCC include surgery, chemotherapy and radiotherapy [8,9]. The indications for radiotherapy in ESCC were less strict than surgical treatment; however, local recurrence is the main reason of failure for ESCC treated by chemoradiotherapy alone [10]. Although Zhang et al. explored the differences in the curative and side effects of chemoradiotherapy on EC among Xinjiang Han, Uygur and Kazakh patients. But their sample size was not large enough, totaling 170 [11]. A piece of study has reported that 5-year OS of ESCC patients undergoing radiotherapy was about10% [8].
Chemotherapy in ESCC is mainly used for advanced disease and distant metastasis, or used with surgery for combined therapy as auxiliary or palliative treatment. Surgery is still the primary treatment modality in most patients with ESCC.
Therefore, understanding the prognostic factors of patients undergoing surgery is of great signi cance for prevention and treatment of EC.

Patient baseline characteristics
The baseline characteristics of these 419 patients were presented in Table 1. 253 patients (60.38%) were more than 60 years old; and 68.26% of the patients were men. 151 and 98 subjects had smoking history and alcohol history, respectively. The tumor was located in the upper chest in 40 cases, in the middle chest in 217 cases, and in the lower chest in 162 cases. The most proportion of patients grade and TNM stage of tumors were moderate and III, respectively. subjects (10.3%) underwent adjuvant radiotherapy, and 51 patients (12.2%) were exposed to chemotherapy and radiotherapy (Fig.1a). Chemotherapy regimens included in all treatments were counted. The primary regimen of chemotherapy was paclitaxel-platinum combined chemotherapy. Fluorouracil (5-FU)-based regimens was the next most common. A minority of patients received oral chemotherapeutic agents (Fig.1b).

Survival and prognostic factors for ESCC
Patients were followed until March 2020 or until death, if earlier. The 1-, 3-, and 5-year overall survival (OS) rates were 84.8%, 47.5%, and 37.3%, respectively, and the median survival time (MST) was 29.0 months (Fig.2). Univariate analysis showed that tumor length, nerve invasion, vascular cancer embolus, sources of patients, nationality, tumor differentiation, tumor stage, lymph node metastasis, stage of disease and pathological type were the factors affecting the OS (Table 2). Multivariate analysis showed that sources of patients, tumor stage, lymph node metastasis and stage of the disease were the independent predictors of OS (Table 3).  Table 4). The rural patients using thoracoscope were present in low proportions (X 2 =14.976 p 0.001, Table 4). Furthermore, the proportion of Kazakh patients in rural areas was signi cantly higher than that in urban areas (X 2 =8.163 p=0.004, Table 4). Finally, we assessed the in uence of sources of patients on OS. No signi cant difference in OS was found in most subgroups, except for the nationality in patients from rural area ( Table 5). In patients from urban area, history of drinking, tumor length, nerve invasion and vascular tumor thrombus were all the independent predictors of OS (Table 6).

Discussion
In this study, we retrospectively analyzed the data of 419 patients with ESCC at a single cancer center in Xinjiang area, which is one of the high-risk regions for esophageal cancer in China. The results showed that the adjuvant therapy for majority of patients were insu ciency by conducting postoperative therapy analyses. In addition to tumor stage, the regions of patients and nationality were also an independent prognostic factor. In further subgroup analysis, we con rmed that nationality was the main factor affecting the prognosis of patients from rural areas.
Our nding that ESCC patients had poor survival and our statistics indicating a lack of postoperative treatment revealed that multidisciplinary treatments, especially adjuvant therapy were essential for patients. Our results also revealed that the future management of these patients from rural area needed to be enhanced with further long-term follow-up data to support clinical decisions and interventional strategies. All of these will have a signi cant impact on the prognosis of patients by in uencing the doctor's follow-up strategy.
In our study, most of them were male and over 60 years old. This is consistent with the results of epidemiological investigations that carcinomas of the esophagus in China occur mainly in people aged 60-74 years and the incidence of EC in men was twice as many as that in women' [7]. In our study, only about 23.6% of the patients were diagnosed with early stage 0 or 1 ESCC, and most of the patients were in middle or late stage. Our stage results are also consistent with the ndings from other studies [12,13]. It has been acknowledged that morbidity of ESCC in the Kazakh population in Xinjiang was far higher than other ethnic minorities [14]. In our study, a worser prognosis was observed in Kazakh patients with ESCC. This is consistent with other study [14].
Additionally, in our multivariate analysis, we found that the source of patients is an important factor affecting the prognosis. This is in agreement with the previously reported data [7,15,16]. Kou et al. analyzed the possible reason for this discrepancy in their nding may lie in the difference of socioeconomic status (SES) disparities in the populations. Our results of subgroup analysis suggested that Kazakh patients from rural area even had a shorter prognosis than other populations living in the same area. This suggest that more attention should be paid to the sources of patients during clinical treatment.
In addition, our results suggested that the adjuvant therapy for majority of patients were insu ciency.
The treatment of ESCC depends on the characteristics of the patient including health status and TNM stage. Current guidelines suggest additional treatment of patients with ≥ T2 tumors, although the risk of node-negative T2 lesions is low [17]. The characteristics of esophageal resection alone can be considered (< 2 cm and well-differentiated), but most subjects with esophageal cancer was locally advanced (> T2 and / or N+) when they were diagnosed [17]. For these patients, to reduce primary tumor bulk chemotherapy, radiotherapy or chemo-radiotherapy isessential. Since about 87% of our patients were in middle or late stage, adjuvant therapy was recommended for most of them according to EC guidelines [18]; however, only 165 subjects received post-surgery treatments. Noticeably, we found that several patients did not receive complete postoperative treatment either for that they lived far from the hospital or for the side effects of the treatment. Our follow-up results revealed that postoperative management of patients with esophageal squamous cell carcinoma needs to be strengthened.
Our results showed that the 1-, 3-, and 5-year OS rates of this patients with ESCC were 84.8%, 47.5%, and 37.3%, which was worse than that was reported in a previous study [19]. In our univariate analysis of the overall survival of the 419 patients, tumor length, nerve invasion, vascular cancer embolus, sources of patients, nationality, tumor differentiation, tumor stage, lymph node metastasis, stage of disease and pathological type were related to OS. The association with tumor length, pT category, pN category, and TNM stage were consistent with the results of other studies [20][21][22]. It is accepted that smoking and drinking alcohol can increase the risk of ESCC from the results of a meta-analysis [23]. However, in our study, age, history of smoking, using thoracoscopy and region of patients were unrelated to their OS. Insu cient adjuvant therapy, diet or environmental factors may lead to lower OS. Therefore, they interferes with other prognostic factors. Some studies showed that older age was a prognostic factor [12,13]. In our univariate analysis, age was not related to OS. Owing to improvements in surgical safety, age is less of a risk factor for the prognosis of ESCC. What's more, one of our ndings disaccorded with others was that the OS of patients with a family history of cancer was longer than the OS of those with no history. This may be due to more active screening and treatments are conducted by patients with a family history of cancer.
This study has some limitations. It is a single institution, retrospective study. The retrospective nature of this study may undermine its power. However, our cancer center is the largest in Xinjiang, which is one of the high-risk regions for esophageal cancer in China. So we believe that our data may provide a better understanding of ESCC in Xinjiang. Until now, few large cohort studies focused on postoperative adjuvant therapy of ESCC in Xinjiang, our results will be useful for the whole management of esophageal cancer.
Of course, further follow-up studies are required to con rm our ndings and develop new therapeutic strategies for these patients.

Conclusion
Adjuvant therapy of these patients with ESCC was shown to be insu cient. Enhanced treatment after surgery needs further improvement. Health sector should implement targeted treatment regime for different areas to alleviate the burden of cancer.

Ethics approval
This study was approved by the medical ethics committee of A liated Tumor Hospital of Xinjiang Medical University.

Consent to Participate
A waiver for informed consent was granted by the medical ethics committee of A liated Tumor Hospital of Xinjiang Medical University.

Consent for publication
Not Applicable.

Data Availability Statement
The data that support the ndings of this study can be available from the corresponding author upon reasonable request.
Authors' contributions we con rmed that all authors have contriubted to and agreed on the content of the manuscript, YLF drafted the manuscript and contributed all tables and gures shown. LT helped analyze the data. ZST and LQ provided suggestions in the discussion. ZQQ, HXJ and TA offered some help in the preparation of manuscript. LXM conceived and took charge of the whole study.