Response-adapted perioperative therapy for resectable esophageal cancer in the immunotherapy era: a narrative review.

Background and Objective: Esophageal cancer is a common malignancy worldwide, and surgery alone is insufficient for most patients with locally advanced disease. Multimodal treatment has therefore become standard practice. In the clinical immunotherapy era, however, it is more complicated to discuss now. There are wider concerns attached to it. The question is no longer limited to whether neoadjuvant therapy is indicated. Multidisciplinary teams must now weigh which treatment backbone is most appropriate, whether radiotherapy adds value over chemotherapy alone, and whether surgery can be delayed in carefully chosen patients. This review summarizes the changes taking place in perioperative care, approaches for making surgical recommendations, and the wider move toward customized control. Methods: The databases of PubMed, Google Scholar, Web of Science, and Cochrane Library were delved into in depth. The inquiry expanded the period from January 1, 2005, to January 31, 2026. Priority was given to phase II/III trials, meta-analyses, guideline documents, and high-quality multicenter studies across time. Key Content and Findings: The standard for esophageal squamous cell carcinoma (ESCC) remains neoadjuvant chemoradiotherapy (nCRT). At the same time, neoadjuvant immunotherapy plus chemotherapy (nICT) emerged as a viable alternative approach with better pathologic response and no clear signal of greater perioperative morbidity. According to the ESOPEC trial, there is a stronger role for perioperative systemic therapy in adenocarcinoma, which was shown by survival being superior with fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) over CROSS-based chemoradiotherapy. The results highlight control of micrometastatic disease. Pathologic complete response (pCR) remains clinically relevant across histological subtypes, but it should not automatically assume that it serves as a surrogate for overall survival especially in the immunotherapy setting. Although organ-preserving approaches show promise, the evaluation of clinical complete response remains imperfect requiring robust surveillance strategies. Biomarkers like mismatch repair status, programmed death-ligand 1 (PD-L1) expression, and circulating tumor DNA can assist in intensifying and de-escalating treatment. Conclusions: The management of resectable esophageal cancer in the perioperative phase is becoming less fixed and more individualized and response-adapted. Further progress will depend on mature survival results, improved biologic selection, and more accurate evaluation of response after induction therapy.