Conversion Therapy for cT4b and M1 Esophageal Squamous Cell Carcinoma: A Comprehensive Systematic Review

Conversion therapy, defined as curative-intent surgery or chemoradiotherapy after induction therapy, is gaining attention in patients with initially unresectable esophageal squamous cell carcinoma due to adjacent organ invasion (cT4b) or distant metastasis (M1). This systematic review aimed to assess survival outcomes, treatment strategies, and the evolving role of immune checkpoint inhibitors in this context. PubMed, Embase, and the Cochrane Library were comprehensively searched to identify studies published between 2010 and 2025 that reported conversion therapy outcomes in patients with esophageal squamous cell carcinoma with cT4b or M1. This review included 15 studies. A 2019 systematic review established the foundation for current practice in cT4b. Subsequent retrospective and prospective studies have reported 5-year overall survival rates of up to 51.6% in patients undergoing salvage or conversion surgery, with no residual tumor (R0) resection rates reaching 98.9% in extended procedures. The ongoing JCOG1510 phase III trial is expected to clarify the optimal strategy. Selected patients undergoing conversion surgery for M1 after induction therapy achieved a 5-year overall survival of 31.7%, with an R0 resection rate of 87%. Survival was not significantly associated with the metastatic site or treatment modality, highlighting the importance of treatment response and multidisciplinary decision-making. The incorporation of immune checkpoint inhibitors into induction regimens expands the pool of candidates eligible for curative-intent local therapy. Conversion therapy may provide durable survival in carefully selected patients, and further prospective studies are warranted to refine patient selection and establish standardized treatment algorithms.