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. 2022 Jul 30;14(15):3721.
doi: 10.3390/cancers14153721.

Trimodal Therapy in Esophageal Squamous Cell Carcinoma: Role of Adjuvant Therapy Following Neoadjuvant Chemoradiation and Surgery

Xiaokun Li  1 , Siyuan Luan  1 , Yushang Yang  1 , Jianfeng Zhou  1 , Qixin Shang  1 , Pinhao Fang  1 , Xin Xiao  1 , Hanlu Zhang  1 , Yong Yuan  1
Affiliations

Trimodal Therapy in Esophageal Squamous Cell Carcinoma: Role of Adjuvant Therapy Following Neoadjuvant Chemoradiation and Surgery

Xiaokun Li et al. Cancers (Basel). .

Abstract

Background: The aim of this study was to determine the role of adjuvant therapy after neoadjuvant chemoradiotherapy and esophagectomy for esophageal squamous cell carcinoma (ESCC). Methods: The study retrospectively reviewed 447 ESCC patients who underwent neoadjuvant chemoradiotherapy and esophagectomy. Patients were divided into an adjuvant therapy group and no adjuvant therapy group. Propensity score matching was used to adjust the confounding factors. Results: 447 patients with clinical positive lymph nodes and no distant metastasis treated with neoadjuvant chemoradiotherapy and esophagectomy were eligible for analysis. After propensity score matching, there were 120 patients remaining in each group. Patients receiving adjuvant therapy had a significantly shorter post-resection overall survival (OS) and disease-free survival (DFS) when compared to patients not receiving adjuvant therapy (log-rank, OS: p = 0.046, DFS: p < 0.001). Receiving adjuvant therapy is not an independently prognostic factor for OS (hazard ratio (HR): 1.270, HR: 0.846−1.906, p = 0.249) but a significantly unfavorable independent prognostic factor for DFS (HR: 2.061, HR: 1.436−2.958, p < 0.001). Conclusions: The results of our study indicate that adjuvant therapy after neoadjuvant chemoradiotherapy and surgery could reduce the OS and DFS in patients with ESCC. Therefore, adjuvant therapy is not recommended for ESCC patients after neoadjuvant chemoradiotherapy and esophagectomy, especially patients without nodal metastases after neoadjuvant therapy.

Keywords: adjuvant therapy; esophageal cancer; esophagectomy; neoadjuvant chemoradiotherapy.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
CONSORT diagram.
Figure 2
Figure 2
After propensity score matching, Kaplan-Meier curves were used to analyze overall survival (OS) and disease-free survival (DFS), and the log-rank test was employed to determine statistical significance between the two groups. (a) Comparison of OS between patients receiving and not receiving adjuvant therapy. Patients receiving adjuvant therapy had a shorter post-resection OS compared with patients not receiving adjuvant therapy (log-rank, OS: p = 0.046) (b) Comparison of DFS between patients receiving and not receiving adjuvant therapy. Patients receiving adjuvant therapy also had a shorter post-resection DFS compared with patients not receiving adjuvant therapy (log-rank, DFS: p < 0.001).
Figure 3
Figure 3
After propensity score matching, Kaplan-Meier curves were used to analyze overall survival (OS) and disease-free survival (DFS), and the log-rank test was employed to determine statistical significance between groups. Subgroup survival analysis were performed stratified by the neoadjuvant treated node (ypN) stage (a) In the patients with ypN1–3, there was no significant difference in OS between two groups (p = 0.500) (b) In the patients with ypN1–3, there was no significant difference in DFS between two groups (p = 0.400) (c) In the patients with ypN0, the adjuvant therapy group yielded a significantly shorter OS compared with non-adjuvant therapy group (p = 0.001) (d) In the patients with ypN0, the adjuvant therapy group yielded a significantly shorter DFS compared with non-adjuvant therapy group (p < 0.001).
Figure 4
Figure 4
Subgroup analysis with Cox regression model. (a) Hazard ratios with 95% CI for the overall survival in prespecified subgroups. For patients with ypN0, adjuvant therapy is an unfavorable factor for OS (HR: 4.274, 95% CI: 1.714–10.654, p = 0.002). For patients with ypN1–3, adjuvant therapy is not a prognostic factor for OS (HR: 0.818, 95% CI: 0.452–1.480, p = 0.506). (b) Hazard ratios with 95% CI for the disease-free survival in prespecified subgroups. For patients with ypN0, adjuvant therapy is an unfavorable factor for DFS (HR: 5.425, 95% CI: 2.490–11.820, p < 0.001). For patients with ypN1–3, adjuvant therapy is not a prognostic factor for DFS (HR: 1.252, 95% CI: 0.734–2.137, p = 0.410).
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