Potential Survival Benefit of Neoadjuvant Docetaxel, Cisplatin and 5-Fluorouracil Therapy in Patients With Esophageal Squamous Cell Carcinoma With Multiple Lymph Node Metastases: A Single-Institute Propensity Score Analysis.

BACKGROUND

Neoadjuvant chemotherapy with fluorouracil, cisplatin, and docetaxel (NAC-DCF) followed by surgery is the current standard of care for resectable advanced esophageal squamous cell cancer (ESCC) in Japan based on the JCOG1109 trial. Although NAC-DCF improves survival, it also increases the risk of febrile neutropenia. Therefore, it is essential to identify tumor factors that predict the greatest benefit from NAC-DCF over conventional fluorouracil and cisplatin chemotherapy (NAC-CF) to optimize patient selection.

METHODS

We retrospectively analyzed patients with resectable advanced ESCC who received either NAC-CF or NAC-DCF at our institution between 2006 and 2019. Propensity score-based inverse probability weighting (IPW) and multivariable adjusted analyses were used to consider baseline differences and compare overall survival (OS) stratified by cTNM factors between groups.

RESULTS

A total of 408 patients received NAC-CF, while 218 received NAC-DCF. NAC-DCF was applied to more advanced patients, with 86% having cT3-4a and 52% having cN2-3 (both p < 0.001). After IPW, the hazard ratio (HR) for OS in the NAC-DCF group was 0.74 [95% confidence interval (CI), 0.55-0.98]. Subgroup analysis showed that patients with cN2-3 had a significant survival benefit with NAC-DCF (HR 0.51; 95% CI, 0.34-0.76) in the IPW analysis, whereas no clear association was observed in those with cN0-1 (HR 0.93; 95% CI, 0.62-1.34), with a nominally significant interaction by clinical N stage (p = 0.039).

CONCLUSION

Neoadjuvant chemotherapy with fluorouracil, cisplatin, and docetaxel (NAC-DCF) was associated with improved survival, with a potential benefit in patients with advanced nodal involvement; however, these findings should be interpreted as hypothesis-generating given the retrospective design.