Objective:

To evaluate the real-world efficacy and prognostic factors of first-line and subsequent-line treatment for first-recurrent/metastatic esophageal squamous cell carcinoma (ESCC).

Approach:

• Study Design: A single-institutional retrospective cohort study evaluating 156 first-recurrent/metastatic ESCC patients treated from January 2018 to January 2023.
• Treatment Comparison: Comparison between two treatment regimens: Immunotherapy+Radiotherapy+Chemotherapy (IT+RT+CT) and Chemotherapy+Immunotherapy (CT+IT).
• Outcome Measures: Assessment of tumor response, progression-free survival (PFS), and overall survival (OS).

Key Findings:

• The IT+RT+CT group had a lower incidence of progressive disease (80.0%) compared to the CT+IT group (90.6%).
• IT+RT+CT showed better PFS compared to CT+IT (HR: 0.50, 95%CI: 0.28-0.90, P = 0.020).
• 1- and 2-year OS rates were significantly higher in the IT+RT+CT group (76.2% and 46.5%) compared to the CT+IT group (39.5% and 19.4%, P = 0.011).
• In a doubly robust Cox model, IT+RT+CT was significantly associated with improved OS compared to CT+IT (HR: 0.48, 95%CI: 0.27-0.85, P = 0.011).

Interpretation:

The study demonstrates that IT+RT+CT as first-line treatment for recurrent/metastatic ESCC is associated with improved PFS and OS compared to CT+IT.

Limitations:

• The study is retrospective and conducted at a single institution, which may limit generalizability.
• Findings require validation in prospective studies to confirm clinical significance.

Conclusion:

The study indicates that IT+RT+CT improves PFS and OS in first-line and subsequent-line treatments for recurrent/metastatic ESCC.