OBJECTIVES: SENTIX was a prospective, single-arm, international multicenter study that evaluated sentinel lymph node biopsy without pelvic lymph node dissection in patients with early-stage cervical cancer. We aimed to evaluate the concordance between preoperative imaging modalities (magnetic resonance imaging (MRI) and ultrasound) and final pathology in the clinical staging of early-stage cervical cancer by post-hoc analysis of the SENTIX study data. METHODS: In total, 47 sites across 18 countries participated in the SENTIX study. Patients with Stage IA1/lymphovascular space invasion-positive to IB2 (International Federation of Gynecology and Obstetrics (FIGO) classification (2018)) cervical cancer, with usual histological types and no suspicious lymph nodes on imaging, were prospectively enrolled between May 2016 and October 2020. Preoperative pelvic clinical staging on either pelvic MRI or ultrasound examination was mandatory. Tumor size discrepancy (< 10 mm vs ≥ 10 mm) between imaging and pathology, as well as the negative predictive value (NPV) of MRI and ultrasound for parametrial involvement and lymph node macrometastasis, were analyzed. RESULTS: Among 690 eligible prospectively enrolled patients, MRI and ultrasound were used as the staging imaging modality in 322 (46.7%) and 298 (43.2%) patients, respectively. A discrepancy of tumor size ≥ 10 mm was reported between ultrasound and final pathology in 39/298 (13.1%) patients and between MRI and pathology in 53/322 (16.5%), with no significant difference in the accuracy of tumor measurement between the two imaging modalities. The NPV of ultrasound in assessing parametrial infiltration and lymph node involvement was 97.0% (95% CI, 0.95-0.99%) and 94.0% (95% CI, 0.91-0.97%), respectively, and that of MRI was 95.3% (95% CI, 0.93-0.98%) and 94.1% (95% CI, 0.92-0.97%), respectively, with no significant differences between the parameters. Ultrasound and MRI were comparable regarding the tumor size measurement (P = 0.452), failure to detect parametrial involvement (P = 0.624) and failure to detect macrometastases in sentinel lymph node (P = 0.876). CONCLUSIONS: Pelvic ultrasound examination and MRI had similar concordance with histology in the assessment of tumor size and of parametrial and lymph node invasion in early-stage cervical cancer. Ultrasound examination should be considered part of preoperative pelvic clinical staging in early-stage cervical cancer, especially in limited-resource regions where MRI is unavailable. © 2025 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

• Keywords
• FIGO, MRI, cervical cancer, clinical staging, imaging, ultrasound,
• MeSH
• Sentinel Lymph Node Biopsy statistics & numerical data   MeSH
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Lymphatic Metastasis diagnostic imaging   MeSH
• Lymph Nodes diagnostic imaging   pathology   MeSH
• Magnetic Resonance Imaging * MeSH
• Uterine Cervical Neoplasms * diagnostic imaging   pathology   surgery   MeSH
• Pelvis * diagnostic imaging   MeSH
• Predictive Value of Tests MeSH
• Preoperative Care methods   MeSH
• Prospective Studies MeSH
• Aged MeSH
• Neoplasm Staging * MeSH
• Ultrasonography * methods   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH

OBJECTIVE: The etiology of inferior oncologic outcomes associated with minimally invasive surgery for early-stage cervical cancer remains unknown. Manipulation of lymph nodes with previously unrecognized low-volume disease might explain this finding. We re-analyzed lymph nodes by pathologic ultrastaging in node-negative patients who recurred in the LACC (Laparoscopic Approach to Cervical Cancer) trial. METHODS: Included patients were drawn from the LACC trial database, had negative lymph nodes on routine pathologic evaluation, and recurred to the abdomen and/or pelvis. Patients without recurrence or without available lymph node tissue were excluded. Paraffin tissue blocks and slides from all lymph nodes removed by lymphadenectomy were re-analyzed per standard ultrastaging protocol aimed at the detection of micrometastases (>0.2 mm and ≤2 mm) and isolated tumor cells (clusters up to 0.2 mm or <200 cells). RESULTS: The study included 20 patients with median age of 42 (range 30-68) years. Most patients were randomized to minimally invasive surgery (90%), had squamous cell carcinoma (65%), FIGO 2009 stage 1B1 (95%), grade 2 (60%) disease, had no adjuvant treatment (75%), and had a single site of recurrence (55%), most commonly at the vaginal cuff (45%). Only one patient had pelvic sidewall recurrence in the absence of other disease sites. The median number of lymph nodes analyzed per patient was 18.5 (range 4-32) for a total of 412 lymph nodes. A total of 621 series and 1242 slides were reviewed centrally by the ultrastaging protocol. No metastatic disease of any size was found in any lymph node. CONCLUSIONS: There were no lymph node low-volume metastases among patients with initially negative lymph nodes who recurred in the LACC trial. Therefore, it is unlikely that manipulation of lymph nodes containing clinically undetected metastases is the underlying cause of the higher local recurrence risk in the minimally invasive arm of the LACC trial.

• Keywords
• lymph nodes, lymphatic metastasis, neoplasm micrometastasis, pathology, uterine cervical neoplasms,
• MeSH
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Lymph Node Excision MeSH
• Lymphatic Metastasis pathology   MeSH
• Lymph Nodes pathology   MeSH
• Neoplasm Micrometastasis pathology   MeSH
• Uterine Cervical Neoplasms * pathology   MeSH
• Aged MeSH
• Neoplasm Staging MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Randomized Controlled Trial MeSH
• Research Support, N.I.H., Extramural MeSH

BACKGROUND: To prospectively assess LLL incidence among cervical cancer patients treated by uterine surgery complemented by SLN biopsy, without PLND. METHODS: A prospective study in 150 patients with stage IA1-IB2 cervical cancer treated by uterine surgery with bilateral SLN biopsy. Objective LLL assessments, based on limb volume increase (LVI) between pre- and postoperative measurements, and subjective patient-perceived swelling were conducted in six-month periods over 24-months post-surgery. RESULTS: The cumulative incidence of LLL at 24 months was 17.3% for mild LLL (LVI 10-19%), 9.2% for moderate LLL (LVI 20-39%), while only one patient (0.7%) developed severe LLL (LVI > 40%). The median interval to LLL onset was nine months. Transient edema resolving without intervention within six months was reported in an additional 22% of patients. Subjective LLL was reported by 10.7% of patients, though only a weak and partial correlation between subjective-report and objective-LVI was found. No risk factor directly related to LLL development was identified. CONCLUSIONS: The replacement of standard PLND by bilateral SLN biopsy in the surgical treatment of cervical cancer does not eliminate the risk of mild to moderate LLL, which develops irrespective of the number of SLN removed.

• Keywords
• cervical cancer, lower limb lymphedema, pelvic lymphadenectomy, sentinel lymph node biopsy,
• Publication type
• Journal Article MeSH

The data on the prognostic significance of low volume metastases in lymph nodes (LN) are inconsistent. The aim of this study was to retrospectively analyze the outcome of a large group of patients treated with sentinel lymph node (SLN) biopsy at a single referral center. Patients with cervical cancer, stage T1a-T2b, common tumor types, negative LN on preoperative staging, treated by primary surgery between 01/2007 and 12/2016, with at least unilateral SLN detection were included. Patients with abandoned radical surgery due to intraoperative SLN positivity detected by frozen section were excluded. All SLNs were postoperatively processed by an intensive protocol for pathological ultrastaging. Altogether, 226 patients were analyzed. Positive LN were detected in 38 (17%) cases; macrometastases (MAC), micrometastases (MIC), isolated tumor cells (ITC) in 14, 16, and 8 patients. With the median follow-up of 65 months, 22 recurrences occurred. Disease-free survival (DFS) reached 90% in the whole group, 93% in LN-negative cases, 89% in cases with MAC, 69% with MIC, and 87% with ITC. The presence of MIC in SLN was associated with significantly decreased DFS and OS. Patients with MIC and MAC should be managed similarly, and SLN ultrastaging should become an integral part of the management of patients with early-stage cervical cancer.

• Keywords
• cervical cancer, isolated tumor cells, micrometastasis, pathological ultrastaging, prognostic parameters, risk of recurrence, sentinel lymph node,
• Publication type
• Journal Article MeSH

The quality of pathological assessment is crucial for the safety of patients with cervical cancer if pelvic lymph node dissection is to be replaced by sentinel lymph node (SLN) biopsy. Central pathology review of SLN pathological ultrastaging was conducted in the prospective SENTIX/European Network of Gynaecological Oncological Trial (ENGOT)-CX2 study. All specimens from at least two patients per site were submitted for the central review. For cases with major or critical deviations, the sites were requested to submit all samples from all additional patients for second-round assessment. From the group of 300 patients, samples from 83 cases from 37 sites were reviewed in the first round. Minor, major, critical, and no deviations were identified in 28%, 19%, 14%, and 39% of cases, respectively. Samples from 26 patients were submitted for the second-round review, with only two major deviations found. In conclusion, a high rate of major or critical deviations was identified in the first round of the central pathology review (28% of samples). This reflects a substantial heterogeneity in current practice, despite trial protocol requirements. The importance of the central review conducted prospectively at the early phase of the trial is demonstrated by a substantial improvement of SLN ultrastaging quality in the second-round review.

• Keywords
• cervical cancer, metastases, sentinel lymph node,
• Publication type
• Journal Article MeSH