The association between recurrence timing and prognosis in patients with locally advanced resectable esophageal cancer undergoing neoadjuvant chemotherapy (NAC) followed by esophagectomy remains unclear. This study aimed to clarify this association using multicenter prospective clinical trial data. Among 162 patients enrolled in a NAC phase II study comparing the efficacy of cisplatin and fluorouracil plus docetaxel with cisplatin and fluorouracil plus adriamycin, 64 patients with recurrence after R0 resection were included in this study. We evaluated the association between recurrence timing and overall survival after recurrence (OSr), along with clinicopathological factors associated with recurrence timing and OSr. Among 64 patients, 46 (71.9%) and 59 (92.2%) experienced recurrence within 1 and 2years after surgery, respectively. Groups based on recurrence timing, including ≤ 6, 6-12, and > 12 months, had median OSr of 3.6, 13.9, and 13.4 months, respectively. The prognosis was significantly poorer for patients with recurrence ≤ 6 months after surgery than for other patients (P < 0.001). Multivariate analysis revealed pathological lymph node staging as an independent factor associated with early recurrence (odds ratio: 3.46, 95% confidence interval: 1.47-8.02, P = 0.0045). On the other hand, multivariate analysis for factors associated with OSr revealed pT (hazard ratio [HR]: 1.91, 95%CI 1.26-2.88, P = 0.0022), early recurrence (HR: 6.88, 95%CI 2.68-17.6, P < 0.001), and treatment after recurrence, with both local treatment (HR: 0.47, 95%CI 0.22-0.98, P = 0.043) and chemotherapy (HR: 0.25, 95%CI 0.11-0.58, P = 0.0011) as independent prognostic factors. Patients with advanced esophageal cancer experiencing recurrence within 6 months after esophagectomy following NAC have an extremely poor prognosis, suggesting that an advanced pN stage is associated with early recurrence.
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