Prospective comparison of diagnostic accuracy of ultrasound, PET / CT and DW ‐ MRI for preoperative assessment of pelvic lymph nodes in cervical cancer patients: results of the CANNES trial

OBJECTIVE: To determine whether ultrasound is non-inferior to positron-emission tomography/computed tomography (PET/CT) and diffusion-weighted magnetic resonance imaging (DW-MRI) in terms of overall diagnostic accuracy for the preoperative assessment of pelvic lymph-node status in cervical cancer. METHODS: This prospective multicenter study reports the primary results of the CANNES trial (NCT05573451), which was conducted at three European gynecological oncology centers and included women with histopathologically confirmed cervical cancer (International Federation of Gynecology and Obstetrics Stage IA1 with lymphovascular space invasion to Stage IIIC2) who underwent ultrasound and PET/CT imaging, with optional DW-MRI, before surgery between January 2021 and December 2023. The diagnostic accuracy for detecting pelvic lymph-node macrometastases (maximum diameter, > 2 mm) was compared with final histopathology (primary reference standard). Furthermore, the diagnostic accuracy for detecting pelvic lymph-node metastases, including both micrometastases (maximum diameter, > 0.2 to ≤ 2 mm) and macrometastases, was compared with final histopathology, or postoperative imaging performed selectively in cases of discordance, specifically when radiologically positive lymph nodes contradicted negative histopathology (secondary reference standard). Sensitivity, specificity and diagnostic accuracy were calculated using the Clopper-Pearson exact method. The diagnostic accuracy of ultrasound for detecting pelvic lymph-node macrometastases and overall lymph-node metastases (including both micro- and macrometastases) was compared with that of PET/CT and that of DW-MRI using McNemar's test; non-inferiority was defined as the lower bound of the 95% CI for the difference in diagnostic accuracy being greater than -10%. RESULTS: During the study period, 141 patients were examined for suspicion of cervical cancer, of whom 120 were analyzed for pelvic lymph-node involvement. All patients underwent ultrasound and PET/CT imaging and 108 (90.0%) also underwent DW-MRI. Pelvic lymph-node macrometastases were confirmed at final histopathology in 29 (24.2%) patients, of whom seven had synchronous micrometastases. An additional seven (5.8%) patients had only micrometastases, resulting in a total of 36 (30.0%) patients with histologically confirmed nodal involvement. Postoperative imaging identified persistent nodal disease in two additional patients, yielding 38 (31.7%) patients with overall pelvic lymph-node involvement. Using the primary reference standard, the sensitivity, specificity and diagnostic accuracy for the detection of pelvic lymph-node macrometastases (per-patient analysis) were 79.3% (95% CI, 60.3-92.0%), 87.9% (95% CI, 79.4-93.8%) and 85.8% (95% CI, 78.3-91.5%), respectively, for ultrasound; 75.9% (95% CI, 56.5-89.7%), 86.8% (95% CI, 78.1-93.0%) and 84.2% (95% CI, 76.4-90.2%), respectively, for PET/CT; and 70.8% (95% CI, 48.9-87.4%), 90.5% (95% CI, 82.1-95.8%) and 86.1% (95% CI, 78.1-92.0%), respectively, for DW-MRI. Using the secondary reference standard, the sensitivity, specificity and diagnostic accuracy values for overall pelvic lymph-node involvement were 68.4% (95% CI, 51.3-82.5%), 90.2% (95% CI, 81.7-95.7%) and 83.3% (95% CI, 75.4-89.5%), respectively, for ultrasound; 65.8% (95% CI, 48.6-80.4%), 89.0% (95% CI, 80.2-94.9%) and 81.7% (95% CI, 73.6-88.1%), respectively, for PET/CT; and 66.7% (95% CI, 48.2-82.0%), 96.0% (95% CI, 88.8-99.2%) and 87.0% (95% CI, 79.2-92.7%), respectively, for DW-MRI. Ultrasound met the predefined non-inferiority margin for overall diagnostic accuracy compared with PET/CT and DW-MRI for both pelvic lymph-node macrometastases and overall pelvic lymph-node involvement. CONCLUSIONS: In this first prospective multicenter trial to directly compare ultrasound, PET/CT and DW-MRI for detecting pelvic nodal disease, ultrasound was non-inferior to PET/CT and DW-MRI in overall diagnostic accuracy, with comparable sensitivity. These findings support ultrasound as a widely accessible and reliable option for preoperative pelvic lymph-node assessment in cervical cancer. © 2026 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.