Does FDG-PET/CT Have a Role in Cervical Nodal Staging for Esophageal Cancer? Results of a Multicenter, Prospective Clinical Trial

Background: Cervical lymph node metastasis (LNM) is common in patients with esophageal cancer. Accurate nodal staging is crucial because treatment strategies can differ when cervical LNM has occurred. Methods: From June 2018 to November 2018, we performed a prospective, open label, clinical research in four institutions in China to assess the value of [18F] fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) for diagnosing cervical LNM of esophageal cancer. A total of 110 patients with resectable esophageal cancer were prospectively enrolled in the study. Esophagectomy with three-field (cervical-mediastinal-abdominal) lymphadenectomy were performed within 2 weeks after FDG-PET/CT scanning. The primary end-point was cervical LNM determined via postoperative histological examination. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of FDG-PET/CT for the assessment of LNM were determined using histological results as reference standards. Findings: The primary cancer exhibited FDG uptake in 107/110 patients (97.2%), with a mean SUVmax of 9.9 ± 6.3. Positive cervical lymph nodes as determined via FDG-PET/CT were detected in 13/110 patients (11.8%). All patients underwent esophagectomy with three-field lymphadenectomy. The median number of lymph nodes resected was 39 (interquartile range 31-46). Cervical LNM occurred in 20 patients (18.2%). With regard to diagnosing cervical LNM, the parameter values associated with FDG-PET/CT were sensitivity 45.0%, specificity 95.6%, positive predictive value 69.2%, negative predictive value 88.7%, and accuracy 86.4%. Of the 110 patients, 90 underwent both FDG-PET/CT scanning and ultrasonography in the neck, and there were no significant differences in sensitivity, specificity, positive predictive value, negative predictive value, or accuracy with respect to cervical LNM diagnosis in these 90 patients. Interpretation: When used to diagnose cervical LNM, PET/CT scanning exhibited high specificity, but low sensitivity, suggesting that it is of limited value for this purpose. Funding Statement: This study was funded by the National Natural Science Foundation of China (Grant 81572253), Shanghai Shen Kang Hospital Development Center City Hospital Emerging Cutting-edge Technology Joint Research Project (Grant SHDC12017102), Shanghai Municipal Health Commission Key Discipline Project (2017ZZ02025), and Ethicon “Excellence in Surgery” (Grant HZB-20181119-23). Declaration of Interests: The authors declare no conflict of interest. Ethics Approval Statement: The study protocol was individually approved by the Institutional Review Boards of all four participating centers. All patients enrolled provided written informed consent.