Neoadjuvant therapy combined with surgery is superior to chemoradiotherapy in esophageal squamous cell cancer patients with resectable supraclavicular lymph node metastasis: a propensity score-matched analysis

Abstract

Background: Multiple clinical trials were conducted to evaluate the efficacy of neoadjuvant therapy in esophageal cancer but exhibited mixed results, indicating that the efficacy of neoadjuvant therapy remains controversial in the treatment of esophageal cancer. Our study was conducted to investigate the value of neoadjuvant therapy in patients with esophageal cancer with supraclavicular lymph node metastases.

Methods: We retrospectively enrolled 231 patients who had resectable esophageal squamous cell carcinoma (ESCC) with supraclavicular lymph node metastases from June 2008 to November 2018. All patients were divided into three groups: the neoadjuvant therapy combined with surgery (Neo + S) group, the radical chemoradiotherapy (CRT) group, and the single radiotherapy (RT) group. Propensity score matching (PSM) was conducted to exclude the impact of potential interferences. Kaplan-Meier analysis, the log-rank test, and competitive risk model analysis were used to assess the efficacy of different therapeutic methods.

Results: Patients in the Neo + S group had a better 3-year survival rate (72.0% vs. 35.8%; P=0.005), progression-free survival (PFS) (24 vs. 14 months; P<0.0001), and lower 3-year tumor-specific mortality risk (25.1% vs. 53.7%; P=0.005) than those in the CRT group. Furthermore, patients in the CRT group had a better 3-year survival (30.1% vs. 18.6%; P=0.012) and lower 3-year tumor-specific mortality risk (57.9% vs. 76.8%; P=0.011) than those in the RT group. Additionally, the supraclavicular lymph node metastasis rate was higher than the mediastinal lymph node metastasis rate in patients with upper esophageal cancer compared to middle and lower esophageal cancer.

Conclusions: Neoadjuvant chemotherapy combined with surgery showed better efficacy than radical CRT in patients who had resectable ESCC with supraclavicular lymph nodes metastasis. Supraclavicular lymph nodes are more likely to be regional lymph nodes for upper and middle esophageal cancer.

Keywords: Esophageal cancer; chemoradiotherapy (CRT); neoadjuvant therapy; propensity score matching (PSM).

Figure 1

Prognostic analysis of patients in the Neo + S, CRT, and RT groups before PSM. (A) The 3-year survival rates of the Neo + S, CRT, and RT groups were 71.3%, 32.3%, and 17.4%, respectively (P<0.0001). The median survival rates of the CRT and RT groups were 20 and 11 months, respectively. (B) PFS in the Neo + S group was significantly better than that in the CRT and RT groups with times of 24, 13, and 9 months, respectively (P<0.0001). (C) The tumor-specific mortality risks of patients in the Neo + S, CRT, and RT groups were 23.7%, 59.6%, and 78.3%, respectively (P<0.001). Neo + S, neoadjuvant therapy combined with surgery; CRT, chemoradiotherapy; RT, radiotherapy; PSM, propensity score matching; PFS, progression-free survival.

Figure 2

Prognostic analysis of patients in the Neo + S, CRT, and RT groups after PSM. (A) The 3-year survival rate of patients in the Neo + S group was significantly higher than that in the CRT group with values of 72.0% and 35.8%, respectively (P=0.005). (B) PFS in the Neo + S group was significantly better than that in the CRT group with durations of 24 and 14 months, respectively (P<0.0001). (C) The 3-year tumor-specific mortality risks of patients in the Neo + S and CRT groups were 25.1% and 53.7%, respectively (P=0.005). (D) The 3-year survival rates of patients in the CRT and RT groups were 30.1% and 18.6%, respectively (P=0.012). (E) PFS of patients in the CRT group was significantly better than that in the RT group (14 and 7 months, respectively; P=0.013). The 3-year tumor-specific mortality risks in the CRT and RT groups were 57.9% and 76.8%, respectively (P=0.011). Neo + S, neoadjuvant therapy combined with surgery; CRT, chemoradiotherapy; RT, radiotherapy; PSM, propensity score matching; PFS, progression-free survival.

Figure 3

Association between tumor location and progression location. The first column represents the number of tumor metastasis or recurrence. The second column indicates the percentage. Data with a value of zero are not shown on the figure. Upper, upper esophageal cancer; middle, middle esophageal cancer; lower, lower esophageal cancer.