Survival Improvements in Recurrent and Metastatic ESCC Cohort
Key Takeaways
- In recurrent/metastatic ESCC in a real-world cohort, first-line IT+RT+CT was associated with significantly longer PFS than CT+IT.
- Across first-line and subsequent-line treatment, OS remained higher with IT+RT+CT than with CT+IT after weighting. Progressive disease or death after first-line treatment occurred in 80% of the IT+RT+CT group versus 90.6% of the CT+IT group, although overall failure-pattern distributions did not significantly differ.
- TNM stage and treatment pattern were independent factors for OS, while tumor length and treatment pattern were independent factors for PFS.
The cohort study retrospectively included 156 patients treated from January 2018 through January 2023 who were aged 18 to 90 years, had pathologically confirmed ESCC, an Eastern Cooperative Oncology Group (ECOG) performance status of 1 to 2, and at least one measurable or evaluable lesion by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Eligibility required either stage IVB disease at diagnosis or first recurrence/metastasis after prior stage I-IVA disease. First-line treatment groupings were RT alone, RT+CT, IT+RT+CT, and CT+IT. For recurrent disease, overall survival (OS) was measured from first recurrence/metastasis to death and progression-free survival (PFS) from first recurrence/metastasis to progression or death; for stage IVB disease, OS was measured from diagnosis to death and PFS from the start of first-line treatment to progression or death.
Across the full cohort, median follow-up was 38 months (IQR 28–77), and 117 deaths were recorded by the time of analysis. Median OS was 17.0 months (95% CI 14.0–21.0), and median PFS was 9.0 months (95% CI 8.0–12.0). Survival in the full cohort remained limited.
In the first-line comparison, IT+RT+CT was associated with longer PFS than CT+IT, with a hazard ratio of 0.50 (95% CI 0.28–0.90; P=0.020). The RT-containing triplet group also had a lower proportion of progression or death after first-line treatment, while the overall distribution of post-treatment outcome categories did not significantly differ across groups. Overall failure-pattern distributions across treatment groups did not significantly differ.
When the comparison was extended across first-line and subsequent-line treatment and reweighted for baseline differences, IPTW-adjusted 1-year and 2-year OS was 76.2% and 46.5% with IT+RT+CT versus 39.5% and 19.4% with CT+IT. In the doubly robust IPTW-Cox model, IT+RT+CT remained associated with better OS than CT+IT, with a hazard ratio of 0.48 (95% CI 0.27–0.85; P=0.011). After adjustment, advanced TNM stage and larger tumor length were also linked to poorer survival.
These treatment contrasts remain observational associations rather than causal effects. Weighting reduced but did not eliminate confounding, and residual imbalance remained in several covariates. PD-L1 expression and baseline tumor burden were not systematically collected, regimen-level chemotherapy, radiotherapy, and immunotherapy detail was not granularly analyzed, and comparative toxicity and quality-of-life analyses across treatment sequences were unavailable. The cohort also reflected heterogeneous prior treatment exposure and did not separate outcomes by recurrence pattern.
Clinician Questions
How were overall survival and progression-free survival defined in stage IVB versus post-treatment recurrent ESCC?
For stage I-IVA ESCC that later recurred or metastasized, OS was measured from first recurrence/metastasis to death and PFS from first recurrence/metastasis to progression or death. For stage IVB ESCC, OS was measured from diagnosis to death and PFS from the start of first-line treatment to progression or death. That difference matters when interpreting survival across a mixed population of recurrent and de novo metastatic ESCC.
What treatments were included in the IT+RT+CT and CT+IT groupings in this recurrent/metastatic ESCC cohort?
For first-line therapy, chemotherapy consisted of paclitaxel plus platinum or fluorouracil plus platinum; in subsequent lines, chemotherapy could be dual-agent or monotherapy tailored to the patient’s condition. PD-1/PD-L1 inhibitors mainly included sintilimab, camrelizumab, tislelizumab, and pembrolizumab given every 3 weeks for 1 to 2 years. RT dosing varied by clinical setting, including definitive, postoperative adjuvant, and locoregional recurrence courses, so the database grouped multimodality strategies rather than testing regimen-specific efficacy within those categories.
What remains unresolved about treatment sequencing in recurrent/metastatic ESCC after this cohort analysis?
The database did not support granular comparisons of specific chemotherapy, radiotherapy, or immunotherapy regimens across sequential lines of therapy and did not provide comparative toxicity or quality-of-life analyses for those sequences. It also did not systematically collect PD-L1 expression or baseline tumor burden for subgroup work and did not sort outcomes by recurrence pattern, such as nodal versus organ metastasis or oligometastatic versus widespread disease.