Sentinel Lymph Node Biopsy in Patients With Early Stages Cervical Cancer

Sentinel lymph node biopsy without systematic pelvic lymphadenectomy in females with early-stage cervical cancer: final outcome of the SENTIX prospective, single-arm, noninferiority, international trial

Sentinel lymph node (SLN) biopsy with ultrastaging is standard in endometrial and vulvar cancers, whereas systematic pelvic lymphadenectomy (PLND) remains recommended in cervical cancer. The SENTIX trial prospectively evaluated the safety of SLN biopsy without PLND in early-stage cervical cancer. Female patients, International Federation of Gynaecology and Obstetrics 2018 stage IA1/LVSI+ to IB2 disease, were enrolled between 2016 and 2020 across 47 sites in 18 countries. All underwent SLN biopsy followed by hysterectomy/trachelectomy. Patients with undetected, unilateral or intraoperatively metastatic SLNs were excluded from the intention-to-treat cohort. SLNs were assessed by pathological ultrastaging. Of 731 patients enrolled, 594 formed the intention-to-treat cohort. SLN metastases were identified in 82 patients (12%), 56.1% intraoperatively and 43.9% by ultrastaging. At 2 years, the recurrence rate was 6.1% (one-sided 95% CI 7.9%), confirming noninferiority to the 7% reference rate. Two-year disease-free and overall survival rates were 93.3% (95% CI 94.9-91.6) and 97.9% (95% CI 98.9-97.0), respectively. Here we show that SLN biopsy without systematic PLND did not increase the risk of recurrence in patients with early-stage cervical cancer. Pathological ultrastaging of SLNs detected about 44% of N1 cases, which would be missed by a standard lymph node assessment. Trial registration: ClinicalTrials.gov ( NCT02494063 ).

Preoperative tumour size assessment in patients with early-stage cervical cancer: Final results of the SENTIX study

Preoperative tumour size is a key prognostic marker in tailoring surgical treatment in early-stage cervical cancer. This post-hoc analysis assessed the accuracy of preoperative tumour size evaluation via imaging, utilizing data from the prospective, international, multicentre SENTIX study that evaluated safety of sentinel lymph node (SLN) biopsy without pelvic lymph node dissection in patients with early-stage cervical cancer. Between 05/2016-09/2020, forty-seven sites across 18 countries enrolled cervical cancer patients (FIGO2018 stages 1A1/lymphovascular-space-invasion-positive to 1B2). Preoperative staging included pelvic MRI or ultrasound as mandatory imaging modalities. All patients underwent primary surgical treatment. Pathological assessment of surgical specimens served as reference standard for evaluating the accuracy of preoperative assessments. Among the 680 included patients, although the mean tumour size discrepancy between preoperative/pathological assessments was only 1.24 ± 8.891 mm, postoperative pT stage was upgraded in 187 (27.5 %) and downgraded in 74 (10.9 %) patients. Discrepancy of ≥10 mm was observed among 155 (22.8 %) patients across all stages, with underestimation in 105 (15.4 %), overestimation in 50 (7.4 %), and a positive correlation (P < 0.0001) between the pathological tumour size and the discrepancy in size assessment. If a maximum 2 cm tumour size threshold were applied to guide the decision between simple and radical hysterectomy, underestimation would result in inadequate surgical management for 9.0 % of patients, whereas overestimation would lead to unnecessarily radical procedures in 5.1 % of cases. The study highlights, that even with the use of modern imaging in preoperative staging, inaccuracies in tumour size assessment remain a common cause of up-/down-staging after surgery resulting in potential inappropriate planning of surgery, and thus in procedure that is either excessively or insufficiently radical. ClinicalTrials.gov: NCT02494063.

Magnetic resonance imaging and ultrasound examination in preoperative pelvic staging of early‐stage cervical cancer: post‐hoc analysis of SENTIX study

ABSTRACTObjectivesSENTIX 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.MethodsIn 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 (&lt; 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.ResultsAmong 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).ConclusionsPelvic 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 &amp; Gynecology published by John Wiley &amp; Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Sentinel lymph node pathological ultrastaging: Final outcome of the Sentix prospective international study in patients with early-stage cervical cancer

To report the outcome of SLN staging in the SENTIX international prospective trial of SLN biopsy in patients with cervical cancer with an intensive ultrastaging protocol and central quality control and to evaluate how the intensity of pathological assessment correlates with metastatic detection rate in SLNs. Eligible were patients with stages T1a1/LVSI+ to T1b2 (90% of patients with N1, is a reasonable compromise for an international standard for ultrastaging. NCT02494063 (ClinicalTrials.gov).

Challenges in lower limb lymphoedema assessment based on limb volume change: Lessons learnt from the SENTIX prospective multicentre study

Lower limb lymphoedema (LLL) is the most disabling adverse effect of surgical staging of pelvic lymph nodes. However, the lack of standardisation of volumetric LLL assessment hinders direct comparison between the studies and makes LLL reporting unreliable. The aim of our study is to report outcomes from a prospective trial that have implications for LLL assessment standardisation. In the prospective international multicentre trial SENTIX, a group of 150 patients with stage IA1-IB2 cervical cancer treated by uterine surgery with bilateral sentinel lymph node biopsy was prospectively evaluated by objective LLL assessment, based on limb volume change (LVC) using circumferrential limb measurements and subjective patient-reported swelling. The assessments were conducted in six-month periods over 24 months post-surgery. Patient LVC substantially fluctuated in both positive and negative directions, which were comparable in frequency up to ±14% change. Thirty-eight patients experienced persistent LVC increase >10% classified as LLL, with nine months median time to onset. Some 34.2% of cases experienced onset later than one year after the surgery. Thirty-three patients (22%) experienced transient oedema characterised as LVC >10%, which resolved without intervention between two consequent follow-up visits. No significant correlation between LVC >10% and a patient-reported swelling was observed. Given that we observed comparable fluctuations of the the lower-limb volumes after surgical treatment of cervical cancer in both positive and negative direction up to ±14%, the diagnostic threshold for LLL diagnosis based on LVC should be increased to >15% LVC. The distinction of transient oedema from persistent LLL requires repeated measurements. Also, as one-third of LLL cases are diagnosed >1-year post-surgery, a sufficient follow-up duration needs to be ensured. Patient-reported swelling correlated poorly with LVC and should only be used as an adjunct to objective LLL assessment. ClinicalTrials.gov: NCT02494063.

Sentinel lymph node mapping and intraoperative assessment in a prospective, international, multicentre, observational trial of patients with cervical cancer: The SENTIX trial

SENTIX (ENGOT-CX2/CEEGOG-CX1) is an international, multicentre, prospective observational trial evaluating sentinel lymph node (SLN) biopsy without pelvic lymph node dissection in patients with early-stage cervical cancer. We report the final preplanned analysis of the secondary end-points: SLN mapping and outcomes of intraoperative SLN pathology. Forty-seven sites (18 countries) with experience of SLN biopsy participated in SENTIX. We preregistered patients with stage IA1/lymphovascular space invasion-positive to IB2 (4 cm or smaller or 2 cm or smaller for fertility-sparing treatment) cervical cancer without suspicious lymph nodes on imaging before surgery. SLN frozen section assessment and pathological ultrastaging were mandatory. Patients were registered postoperatively if SLN were bilaterally detected in the pelvis, and frozen sections were negative. ClinicalTrials.gov (NCT02494063). We analysed data for 395 preregistered patients. Bilateral detection was achieved in 91% (355/395), and it was unaffected by tumour size, tumour stage or body mass index, but it was lower in older patients, in patients who underwent open surgery, and in sites with fewer cases. No SLN were found outside the seven anatomical pelvic regions. Most SLN and positive SLN were localised below the common iliac artery bifurcation. Single positive SLN above the iliac bifurcation were found in 2% of cases. Frozen sections failed to detect 54% of positive lymph nodes (pN1), including 28% of cases with macrometastases and 90% with micrometastases. SLN biopsy can achieve high bilateral SLN detection in patients with tumours of 4 cm or smaller. At experienced centres, all SLN were found in the pelvis, and most were located below the iliac vessel bifurcation. SLN frozen section assessment is an unreliable tool for intraoperative triage because it only detects about half of N1 cases.

A. Burgetova

Alessandro Buda

Barbara Kipp

David Cibula

Ignacio Zapardiel

Kristýna Němejcová

Luc R.C.W. van Lonkhuijzen

Martin Michal

Sylva Bajsova