The Therapeutic Modalities And Prognostic Factors Of Primary Small Cell Carcinoma Of Esophagus

BackgroundPrimary small cell carcinoma of the esophagus(PSCCE)is a relatively rare malignancy,accounting for 0.5-2.8% of all esophageal malignancies.With a high degree of malignancy,the 5-year survival rate of patients with PSCCE was only 4.8% and the median survival time of untreated PSCCE patients was no more than 4 months.As one of the most common type of extrapulmonary small cell carcinoma,PSCCE was reported for the first time in 1952 by McKeown and gradually became a research hotspot.More and more articles were published regarding the epidemiological characteristics,clinicalpathological features,treatments,prognosis and molecular biology of PSCCE patients.But the optimal treatment patterns still exist a lot of controversy because of its low morbidity and high biological malignancy.At present,considering the similarity of biological behaviours between small cell carcinoma of lung and esophagus,multi-disciplinary comprehensive treatment mode was widely used,including surgery,radiotherapy and chemotherapy.Its validity has been confirmed in many studies,but how to maximize the therapeutic effect of different therapeutic methods still exists controversy.According to the first edition of clinical practice guidelines for neuroendocrine tumor 2019 issued by NCCN(National Comprehensive Cancer Network),surgical resection + adjuvant chemotherapy radiotherapy,neoadjuvant chemotherapy radiotherapy + surgical resection,chemotherapy alone,radiotherapy alone and chemoradiotherapy can be selected for resectable small cell extrapulmonary cancer.For locally advanced and unresectable extrapulmonary small cell carcinoma,concurrent chemoradiotherapy or sequential chemoradiotherapy or simple chemotherapy can be selected.Chemotherapy is recommended for extrapulmonary small cell carcinoma with distant metastasis.ObjectivePrimary small cell carcinoma of the esophagus(PSCCE)is a relatively rare,high malignant tumor and the diagnosis is associated with distant metastasis and poor prognosis.The optimal treatment of primary small cell carcinoma of the esophagus is still lack of concensus due to a lack of large sample clinical research and the effectiveness of multi-disciplinary therapeutic methods has been confirmed by a lot of published researches.After further study of all previous published data regarding primary small cell carcinoma of the esophagus,this study explored the efficacy and prognostic factors and comprehensive treatment models of primary small cell carcinoma of the esophagus.MethodsThe research analyzed retrospectively the general information of 106 patients with complete follow-up data collected from the First Affiliated Hospital of Zhengzhou University between Jan.2011 and Dec.2018,including gender,age,initial symptoms(including food and a lot of retrosternal pain,upper abdominal pain,cough,hoarseness,neck bag piece,etc.),lesion location,lesion length,lesions morphology,immunohistochemical results.According to The 7th edition of AJCC(The American Joint Committee on Cancer)? TNM(Tumor,Lymph Node,Metastasis)staging of esophageal cancer,stage I could be seen in 8 patients,stage II in 34 patients,stage III in 18 patients,and stage IV in 29 patients.According to The VALSG(The Veterans Administration Lung Study Group)staging method(67 patients were in the limited stage and 29 patients were in the extensive stage).Univariate analysis was used to analyze the effect of various clinicopathological indicators on the prognosis of patients with primary small cell esophageal carcinoma.Multivariate Cox regression model was used to analyze the independent prognostic factors of primary small cell esophageal carcinoma.Kaplan-meier survival curve and log-rank test were used to analyze the effect of different treatment methods on the prognosis of patients with primary small cell esophageal cancer.Results1.Lymph node metastasis(P=0.009),local limited or extensive stage(P=0.001),and chemotherapy(P=0.018)were independent prognostic factors for PSCCE patients;2.The overall survival time of patients with limited stage could be prolonged by surgery(median survival: 24.0 vs.8.0 months,P=0.0002),but the smae results were abscent in patients with extensive stage(median survival: 9.0 vs 10.5 months;P = 0.7257);3.Postoperative adjuvant chemotherapy can have a positive effect on stage III patients(median survival: 26.0 vs 10.0 months,P=0.0076),which is not recommended for stage I and II patients(P=0.3221;P = 0.2742);4.Systemic chemotherapy could improve the prognosis of patients in the extensive stage in this study(median survival was 10.0 vs 4.5 months,P = 0.0475);5.For patients with limited stage of small cell carcinoma of the esophagus,seven different therapeutic models including chemotherapy only,surgery and adjuvant chemotherapy,neoadjuvant chemotherapy and surgery,surgery only,radiotherapy and chemotherapy,surgery plus radiotherapy plus chemotherapy,have statistically significant differences(P = 0.0018).Neoadjuvant chemotherapy plus surgery and surgery plus adjuvant chemotherapy plus radiotherapy in patients with a median survival period is longer than the other;6.Among the patients with extensive stage,there was no statistical significance in the prognosis between the six treatment modes including chemotherapy alone,surgery + adjuvant chemotherapy,neoadjuvant chemotherapy + surgery,surgery alone,radiotherapy,and no treatment(P=0.5820),but the median survival time of the patients with new chemotherapy alone was longer.ConciusionFor patients with limited stage and resectable lesions,surgery is still the preferred treatment.Postoperative adjuvant chemotherapy is recommended for patients with stage III,and patients with stage I and II can be followed up regularly after surgery.Neoadjuvant chemotherapy,radiotherapy,chemotherapy or combination of radiotherapy and chemotherapy may be selected for locally advanced locally limited small-cell esophageal carcinoma,but the optimal treatment mode still needs further study.Patients with extensive stage should proactively receive comprehensive treatment mainly based on chemotherapy.Lymph node metastasis,VALSG staging and chemotherapy were independent prognostic factors of PSCCE patients.