Abstract Background The optimal treatment strategy for limited-stage small cell esophageal carcinoma (LS-SCEC) remains uncertain, we aimed to evaluate the efficacy of perioperative therapy in those patients. Methods From June 2005 to November 2022, a total of 156 patients with LS-SCEC who underwent esophagectomy were included in the current study. The primary endpoint was overall survival, and secondary endpoints included progression-free survival. Pathologic staging was determined based on the 8th American Joint Committee on Cancer (AJCC) TNM staging system for esophageal carcinoma. Survival curves were created using the Kaplan-Meier method and compared using the log-rank test. Prognostic factors analysis was carried out using both univariate and multivariate Cox regression models, as well as propensity score matching (PSM) analysis. Statistical significance was defined as P value < 0.05 in a two-tailed test. Results Among 156 LS-SCEC patients, the median age was 62 years (interquartile range [IQR], 56-67), with 120 (76.9%) being males. Thirty-three (21.2%) patients received neoadjuvant chemotherapy; and 2 (1.3%) received neoadjuvant chemoradiotherapy. Seventy-six (48.7%) received adjuvant chemotherapy, 2 (1.3%) received adjuvant radiotherapy, and 13 (8.3%) received adjuvant chemoradiotherapy. Only 7 (4.5%) patients achieved pathological complete remission after neoadjuvant therapy. Following surgery, 33 (21.2%) patients were categorized stage I, 40 (25.6%) as stage II, 61 (39.1%) as stage III, and 22 (14.1%) as stage IV. The median follow-up time of the entire cohort was 72 months. The median disease-free survival (mDFS) was 12.0 months (95% CI, 10.2–13.8 months), and the median overall survival (mOS) was 21.0 months (95% CI, 16.2–25.8 months). The 5-year OS rate was 25.9%, and the DFS rate was 21.9%. Univariate analysis revealed that clinical T stage (P=0.011), clinical N stage (P=0.009), pathological T stage (P=0.027), pathological N stage (P=0.001), pathological TNM stage (P=0.002), adjuvant therapy (P<0.001), and neural invasion (P=0.001) were significant prognostic factors for overall survival. In multivariate analysis, clinical T stage (P=0.049), neural invasion (P=0.002), N stage (P=0.006), and adjuvant therapy (P=0.001) were identified as independent prognostic factors. Furthermore, a PSM analysis was conducted to evaluate the impact of neoadjuvant chemotherapy on LS-SCEC patients. Following PSM, 64 patients were matched, with 32 in each group. Both univariate and multivariate analyses indicated that neoadjuvant chemotherapy could enhance the OS of LS-SCEC patients, with a 5-year OS rate of 37.7% compared to 0.0% in the non-neoadjuvant chemotherapy group (P<0.001, HR=0.319, 95% CI: 0.168-0.604). Subgroup analyses further supported the benefit of neoadjuvant chemotherapy for patients with clinical stages T3-4 and nodal positive (N+), where improved outcomes were observed (P=0.001 and 0.013 respectively). Additionally, subgroup analyses revealed that adjuvant chemoradiotherapy was identified as the optimal treatment model for patients with nodal positive status (adjuvant chemoradiotherapy vs. chemotherapy: OS P=0.01, DFS P=0.004) and those categorized as pathological stage III-IV (adjuvant chemoradiotherapy vs. chemotherapy: OS P=0.03, DFS P=0.017). Conclusions Perioperative therapy is essential for patients with LS-SCEC. Patients with clinical stage T3-4 and nodal positive should undergo neoadjuvant chemotherapy. All patients should receive adjuvant therapy, and adjuvant chemoradiotherapy is recommended for those with nodal involvement or pathologic TNM stages III-IV.
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