ABSTRACT 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.
Higaki et al. (Sun,) studied this question.