Standardized MRI and Structured Reporting for Esophageal Squamous Cell Carcinoma

This investigator-initiated, prospective, multicenter, dual-cohort diagnostic accuracy study uses a common standardized 3.0-T esophageal MRI framework. The clinical treatment pathway, including whether a patient proceeds directly to surgery or receives neoadjuvant therapy before surgery, is determined by the treating multidisciplinary team independently of study participation. The MRI examinations are performed as part of routine clinical care. Participants are classified into one of two cohorts according to their clinical pathway.

Cohort A includes patients who have received no antitumor treatment before MRI and are scheduled for upfront esophagectomy. MRI is performed within 14 days before surgery. Structured MRI-based T stage (mrT1, mrT2, mrT3, or mrT4a) is compared with postoperative pathological T stage.

Cohort B includes patients scheduled to receive neoadjuvant chemoradiotherapy, chemotherapy, or immunotherapy combined with chemotherapy according to routine clinical decision-making, followed by esophagectomy. Baseline MRI is performed within 14 days before neoadjuvant treatment, and a second MRI is performed after treatment and within 14 days before surgery. Paired examinations are assigned an MRI tumor regression grade (mrTRG 1-4) and compared with pathological tumor regression grade in the resected primary tumor bed using the modified Ryan system (pTRG 0-3). Pathological good response is defined as pTRG 0-1, and the prespecified imaging dichotomy is mrTRG 1-2 versus mrTRG 3-4.

The core MRI framework includes large-coverage T2-weighted imaging, tumor-axis and high-resolution oblique axial T2-weighted imaging, diffusion-weighted imaging with apparent diffusion coefficient maps, and three-dimensional T1-weighted imaging before and after gadolinium contrast administration. Participating scanners undergo parameter mapping, test-scan certification, and ongoing central quality control.

Each examination is interpreted independently by two trained radiologists who are blinded to postoperative pathology, other imaging-stage results, endoscopic stage, and clinical response conclusions. Disagreements are adjudicated by a third senior radiologist. Pathological pT or pTRG is assessed by two gastrointestinal pathologists blinded to the MRI results, with adjudication when needed. At least 10% of cases are reread after an interval of at least 4 weeks to assess intrareader agreement.

A total of 500 participants are planned, with 250 participants in each cohort. Consecutive enrollment will be used, and no single center should contribute more than 40% of the total sample. The study evaluates only the primary esophageal tumor. Lymph-node imaging features, N stage, and nodal treatment response are not collected for research analysis.

Inclusion criteria

• Age 18 to 80 years, inclusive
• Histologically confirmed esophageal squamous cell carcinoma based on endoscopic biopsy or other tissue examination
• Primary tumor located in the thoracic esophagus
• Planned curative esophagectomy
• Able to complete the required esophageal MRI examination with diagnostically adequate image quality
• Able and willing to provide written informed consent
• For Cohort A: no chemotherapy, radiotherapy, immunotherapy, targeted therapy, or other antitumor treatment before MRI; surgery planned within 14 days after MRI; and postoperative pathological T stage expected to be available
• For Cohort B: neoadjuvant treatment followed by surgery selected by the clinical multidisciplinary team; baseline MRI completed within 14 days before neoadjuvant treatment; post-treatment MRI completed within 14 days before surgery; and pathological tumor regression grade of the primary tumor bed expected to be available

Exclusion criteria

• Adenocarcinoma, neuroendocrine carcinoma, adenosquamous carcinoma, or another non-squamous histological type
• Cervical esophageal cancer, a gastric primary tumor extending into the esophagus, or multiple primary lesions that prevent reliable imaging-pathology matching
• Definite distant metastasis, unresectable T4b disease, or another reason that prevents acquisition of a surgical pathological reference standard
• Previous esophageal cancer surgery, radiotherapy, or another treatment that substantially altered local esophageal anatomy
• Contraindication to MRI, or contraindication to the gadolinium-based contrast agent when the required contrast-enhanced sequences cannot be completed
• Severe claustrophobia, inability to follow breathing instructions, or another cause of nondiagnostic image quality that persists after a safe repeat examination
• Substantial disease progression, emergency intervention, or off-protocol treatment between MRI and surgery that prevents valid imaging-pathology comparison
• Inadequate surgical specimen sampling or inability to determine pathological T stage or pathological tumor regression grade