Objective:

To compare the efficacy and survival outcomes of upfront definitive chemoradiotherapy (DCRT) versus salvage DCRT after unsuccessful conversion therapy in patients with locally advanced unresectable esophageal squamous cell carcinoma (ESCC), highlighting the differences in treatment approaches.

Key Findings:

• The overall objective remission rate (ORR) was 68.29% in the salvage group compared to 26.00% in the upfront group (P < 0.001).
• Progression-free survival (PFS) was significantly longer in the salvage group (20.3 months, 95% CI: 11.6-28.9) compared to the upfront group (6.4 months, HR 0.36, P = 0.001).
• Median overall survival (OS) was 42.2 months in the salvage group versus 15.9 months in the upfront group (HR 0.39, P = 0.001).
• 1-year OS rates were 95.1% for the salvage group and 56.9% for the upfront group; 2-year OS rates were 68.8% and 36.6%, respectively.

Interpretation:

Salvage DCRT after conversion therapy significantly improves survival outcomes in patients with locally advanced unresectable ESCC compared to upfront DCRT, suggesting a potential new treatment paradigm that could reshape clinical practice.

Limitations:

• Retrospective design may introduce selection bias.
• Limited generalizability due to the specific patient population and treatment centers involved.
• Potential confounding factors inherent in retrospective studies.

Conclusion:

Salvage DCRT demonstrates superior survival outcomes compared to upfront DCRT in patients with locally advanced unresectable ESCC, warranting further prospective randomized trials to validate these findings.