Definitive concurrent chemoradiotherapy (dCRT) remains the treatment backbone for anatomically unresectable locally advanced esophageal squamous cell carcinoma (ESCC), but recurrence after treatment remains relatively common. This review discusses the use of immune checkpoint inhibitors concurrently, as induction therapy, and as consolidation or maintenance therapy after dCRT. Anatomical unresectability is distinguished from medical inoperability, refusal of surgery, and organ-preservation pathways. Early studies support the feasibility of combination treatment, but differences in study populations, treatment exposure, and endpoint time origins limit comparisons across studies. EC-CRT-002 has not established a universal benefit from prolonged immunotherapy, and its historical-control comparisons should be distinguished from the randomized groups receiving different treatment durations. Studies also differ in the reporting of severe toxicity, treatment discontinuation, fistula, and treatment-related death and in the populations analyzed. Dynamic circulating tumor DNA is associated with response and survival, but no evidence has established a treatment-by-biomarker interaction for the additional benefit of immunotherapy. Confirmatory randomized studies in clearly defined target populations are still needed.
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