Efficacy comparison of first-line treatment regimens for stage IV esophageal squamous cell carcinoma with supraclavicular lymph node metastasis: A study of the oligometastatic subtype.

BACKGROUND: Supraclavicular lymph node metastasis (SLNM) is a common subtype of oligometastatic stage IV esophageal squamous cell carcinoma (ESCC), with a better prognosis than multifocal metastatic disease. However, the optimal first-line treatment strategy for this specific subgroup remains unclear. OBJECTIVES: This study evaluated the efficacy and safety of three first-line treatment modalities-chemoimmunotherapy (CI), concurrent chemoradiotherapy (CCRT), and chemoimmunotherapy followed by radiotherapy (CIRT)-in patients with ESCC with SLNM. DESIGN: This retrospective, multicenter cohort study analyzed data from 484 ESCC patients with SLNM treated at three major cancer centers in China. METHODS: Data from 484 patients between January 2019 and December 2024 were analyzed. Inverse probability of treatment weighting (IPTW) was applied to reduce selection bias. PFS and OS were estimated using the Kaplan-Meier method. Intergroup differences were compared using the log-rank test. The Fine-Gray competing risks model was applied to both unweighted and weighted cohorts to calculate the cumulative incidence. Cumulative incidence functions (CIF) were estimated using the Aalen-Johansen method. A two-sided P value < 0.05 was considered statistically significant. RESULTS: The CI, CCRT, and CIRT groups enrolled 145, 137, and 202 patients. In weighted Cox regression analysis, CIRT demonstrated superior PFS (adjusted HR (aHR)=0.73, 95% CI: 0.53-0.99, P=0.043) and OS (aHR=0.48, 95% CI: 0.31-0.75, P=0.001) compared to CI. CIRT demonstrated superior PFS compared with CCRT (HR = 0.67, 95% CI: 0.52-0.87, P = 0.003). The weighted median PFS in each group was as follows: CI group 11.0 months (95% CI: 8.0-15.0), CCRT group 11.0 months (95% CI: 10.0-14.0), CIRT group 16.0 months (95% CI: 13.0-20.0) (P = 0.002). CONCLUSION: Compared with CI (systemic therapy alone), CIRT demonstrated potential advantages in PFS, OS, and locoregional control while maintaining acceptable toxicity. Compared with CCRT, CIRT demonstrated improved PFS with no significant differences in OS or locoregional recurrence. These findings suggest that CIRT may represent a promising first-line treatment option for patients with ESCC and SLNM.