Real-world safety and efficacy of neoadjuvant docetaxel, cisplatin, and 5-fluorouracil therapy for locally advanced esophageal squamous cell carcinoma.

Background: Neoadjuvant chemotherapy with docetaxel, cisplatin plus 5-FU (DCF) has become the new standard of care for locally advanced esophageal squamous cell carcinoma (ESCC). In a real-world setting, the efficacy, recurrence, and adverse events (AEs) remain unclear.

Methods: This retrospective cohort study included 86 patients who received neoadjuvant DCF followed by esophagectomy for resectable ESCC.

Results: Following neoadjuvant DCF treatment, 75 patients underwent R0 curative resection. At the median follow-up of 19.2 months, the median disease-free survival (DFS)/recurrence-free survival (RFS) was not yet reached, with estimated 3-year DFS/RFS rates of 65.2%, respectively. The incidence of primary tumor regression grading (TRG) grade 1a and pathological complete response (pCR) were 21.3% (16/75) and 14.7% (11/75), respectively. The estimated 1-year DFS/RFS rates were 93.8% for primary TRG grade 1a and 100% for pCR. Baseline elevated serum SCC-antigen levels were inversely associated with achieving primary TRG grade 1a or pCR. In 64 patients who did not achieve pCR, residual tumor cells in the lymph nodes (ypN; HR, 16.96; 95% CI, 2.11-136.12; P < 0.01) and Glasgow prognostic score (GPS; HR, 8.34; 95% CI, 1.73-40.31; P < 0.01) were independent predictors of shorter DFS/RFS. The most common grade ≥ 3 AEs were neutropenia (61.6%) and febrile neutropenia (26.7%), which were not associated with clinicopathological factors. The most common non-hematological AEs were appetite loss (9.3%), pulmonary embolism (8.1%), diarrhea (7.0%), and nausea (2.3%). Nine patients discontinued neoadjuvant DCF due to toxicities.

Conclusions: Neoadjuvant DCF was effective and well-tolerated in real-world ESCC patients. Primary TRG grade 1a or pCR showed a favorable DFS/RFS, while positive ypN and GPS were independent risk factors for worse DFS/RFS.