Esophageal cancer (EC) remains one of the most common malignancies of the digestive system globally. In particular, two-thirds of EC cases in East Asia are squamous cell carcinoma subtype.1,2 The current standard of care for resectable locally advanced esophageal squamous cell carcinoma (ESCC) consists of neoadjuvant therapy followed by radical resection. However, therapeutic responses to neoadjuvant therapy vary markedly among individuals; meaning while some patients achieve major or complete pathological remission, others show minimal tumor regression or even further disease progression.3 Thus, identifying responders prior to surgery is critical. Furthermore, early assessment of changes in the primary tumor, lymph node involvement, and distant metastases during therapy is essential for optimizing subsequent treatment strategies. Such assessment requires imaging modalities capable of detecting early metabolic alterations, not merely anatomical changes.

Functional imaging with [18F]fluorodeoxyglucose ([18F]FDG) PET/CT enables quantitative evaluation of tumor glucose metabolism and viability independently from morphological changes, providing a more accurate estimate of tumor burden compared to anatomical imaging alone.4 In patients with advanced ESCC who receive various neoadjuvant treatment regimens, [18F]FDG PET/CT metabolic response has consistently been shown to predict pathologic response and survival outcomes.5, 6, 7, 8, 9, 10, 11, 12, 13 More recently, alternative radiotracers such as [18F] or [68Ga]Ga-labeled fibroblast activation protein inhibitors (FAPI) PET/CT have demonstrated the potential for visualizing the tumor microenvironment and predicting treatment response in ESCC (Table 1).14,15

The emergence of total-body PET/CT (TB PET/CT) systems with 194-cm long-axial field-of-view (LAFOV) (uEXPLORER, United Imaging Healthcare Co.Ltd., Shanghai, China) represents a major technological advance in molecular imaging. Compared with conventional scanners, TB PET/CT provides higher signal collection efficiency, mostly due to greater anatomic coverage, which coupled together with improved spatial resolution allows for reduced image noise, improved lesion detectability, low-dose protocols, ultrafast scanning, and comprehensive whole-body dynamic imaging.16,17 These features expand the clinical potential of molecular imaging to a more comprehensive full-body metabolic response assessment, offering new insights into both disease and healthy tissues.

Despite its promising advantages, studies applying TB PET/CT to assess metabolic response in ESCC remain scarce. Hence, this narrative review aims to summarize the current evidence on conventional PET/CT for metabolic response evaluation in advanced ESCC, highlight the technological advantages of TB PET/CT, and discuss its feasibility and potential clinical impact based on existing literature and our institutional experience.