Long-term survival, recurrence patterns, and postrecurrence outcomes after neoadjuvant chemoradiotherapy versus surgery plus adjuvant therapy in locally advanced esophageal squamous cell carcinoma: Final results of a randomized phase III trial.

Abstract

e16092 Background: The optimal treatment strategy for locally advanced esophageal squamous cell carcinoma (ESCC) remains uncertain. Although neoadjuvant chemoradiotherapy (NCRT) improves pathological response, its long-term survival advantage over surgery plus adjuvant therapy (AT) is unclear. The impact of these strategies on recurrence patterns and postrecurrence survival (PRS) also requires clarification. Methods: In this prospective, open-label, randomized phase III trial, 245 patients with cT1N+M0 or cT2–4aNxM0 thoracic ESCC (2018–2020) were assigned to NCRT followed by surgery or surgery plus AT; 118 and 112 patients were included in the final analysis. NCRT consisted of IMRT (40 Gy/20 fractions) with weekly paclitaxel and carboplatin. AT was individualized by a multidisciplinary team. The primary endpoint was overall survival (OS); secondary endpoints included disease-free survival (DFS), pathological outcomes, recurrence patterns, recurrence timing, and PRS. Results: After a median follow-up of 59.1 months, OS and DFS did not differ significantly between groups (5-year OS: 59.2% vs 59.6%, HR 1.01, P = 0.97; 5-year DFS: 53.1% vs 56.5%, HR 1.13, P = 0.53). The NCRT group achieved a 28.8% pathological complete response (pCR) rate, and pCR was associated with markedly improved OS (76.5% vs 52.1%; HR 0.39, P = 0.01). Among 230 evaluable patients, the recurrence rate was 33.5% (34.7% vs 32.1%, P = 0.696), with distant metastasis as the predominant pattern. Early recurrence ( < 12 months) occurred in 14.3% of patients and predicted significantly poorer OS (6.1% vs 27.1%; HR 4.22, P < 0.001) and shorter PRS (6.93 vs 10.28 months; HR 1.75, P = 0.026). It was the only independent predictor of PRS. Conclusions: NCRT did not improve long-term survival over surgery plus AT in an unselected ESCC population. Nevertheless, patients achieving pCR experienced substantial benefit. Recurrence remained common, dominated by distant metastasis, and early recurrence was strongly associated with poor PRS. Clinical trial information: NCT06775652 .