Multimodal Treatment Strategies to Improve the Prognosis of Locally Advanced Thoracic Esophageal Squamous Cell Carcinoma: A Narrative Review

Simple Summary Esophageal squamous cell carcinoma with invasion to other organs/structures is considered unresectable, and its prognosis is extremely poor. In Japan, definitive chemoradiotherapy is often selected for cT4b cases, and regarded as the standard treatment option. In recent years, conversion surgery has been applied in some cases after downstage by induction therapy. In particular, DCF therapy consisting of docetaxel, cisplatin, and 5-fluorouracil has been reported effective for cT4b cases. Induction chemoradiotherapy, followed by conversion surgery, and salvage surgery after definitive chemoradiotherapy, have also been performed in selected patients. This article provides an overview of the contribution of multimodal treatment to improve oncological and survival outcomes for patients with locally advanced unresectable esophageal squamous cell carcinoma. Esophageal cancer is the seventh most common malignancy and sixth most common cause of cancer-related death globally. Esophageal squamous cell carcinoma (ESCC) with aortic or tracheal invasion is considered unresectable, and has an extremely poor prognosis; its standard treatment is definitive chemoradiotherapy (dCRT). In recent years, induction chemotherapy (ICT) has been reported to yield high response rates for locally advanced ESCC, and the efficacy and safety of ICT followed by conversion surgery (CS) have been investigated. Multimodal treatment, combining surgery with induction chemoradiotherapy (ICRT) or ICT, is necessary to improve ESCC prognosis. CS is generally performed for locally advanced ECC after ICRT or ICT when tumor downstaging is achieved, although its prognostic benefit remains controversial. The Japan Clinical Oncology Group (JCOG) has conducted a three-arm phase III randomized controlled trial (JCOG1510) to confirm the superiority of DCF (docetaxel, cisplatin, and 5-fluorouracil) ICT, over conventional dCRT, among patients with initially unresectable ESCC. In recent years, researchers have reported favorable outcomes of induction therapy followed by CS and salvage surgery, after dCRT or systemic immunochemotherapy. In this review, we will describe the latest developments in the multimodal treatment including chemotherapy, CRT, surgery, and immunotherapy, which may improve oncological and survival outcomes for patients with cT4 ESCC.