Assessment of sentinel lymph node biopsy procedure for detecting lymph node spread in women diagnosed with cervical cancer.

Not yet recruiting

Conditions: Malignant neoplasm of cervix uteri, unspecified,

Registration Number: CTRI/2025/06/089643

Lead Sponsor: Tata Memorial Center

Brief Summary: Cervical cancer is a major contributor of cancer burden in India with an incidence of 1,27,526 new cases detected in 2022 and 79,906 deaths.

Only 20% of early stage cervical cancer patients have been found to have positive lymph nodes and the rest receive morbid procedure of systematic lymphadenectomy without any therapeutic benefit. The lymphnode positive patients are candidates for adjuvant concurrent chemoradiation (CCRT) and have to face the associated toxicity of dual modality treatment.

SLNB procedure has been evaluated in cervical cancers in various retrospective studies, few prospective studies and meta-analyses.

One of the first validation studies was SENTICOL, which showed very good sensitivity of 92%, Negative predictive value of 98.2%, bilateral detection rate of 76.5% . Subsequently, the most recent meta-analysis by Zhang et al showed a pooled side specific sensitivity of 88% . These outstanding results were obtained despite the use of traditional blue dye with radiocolloid and without ultrastaging. The debate regarding the choice of the dye has been put to rest by the FILM study, which has undeniably pointed towards the superiority of ICG.

TThe quality of life issues and onocological safety have been addressed in the subsequent SENTICOL 2 study. Lymphatic morbidity was significantly lower in the SLN arm (31.4%) compared to the SLN + PLND arm (51.5%; p = 0.0046), as was the rate of postoperative neurological symptoms (7.8% vs. 20.6%, p = 0.01, respectively(Mathevet Patrice). It demonstrated no significant difference in disease free survival (89.5 & 93.1%) or overall survival (95.2 & 96%) between the two groups as a secondary end point. SENTICOL 3 is a large ongoing study investigating the same aspect .

Unlike endometrial carcinoma, intraoperative detection of lymphnode metastasis plays a major role in carcinoma cervix. Landmark study by Landoni et al advocated to avoid dual modality treatment due to increased morbidity without added survival benefit. Hence, lymphnodes if found positive on intra operative frozen section analysis(FSA), results in termination of the surgical procedure, and definitive concurrent chemoradiation.

The SENTIX trial has assessed the role of FSA on sentinel lymphnodes. They have reported a sensitivity of 46%. This included detection of 83% of the macro-metastasis and 26.3% of the micro-metastasis by FSA. The rest were detected on intensive ultra-staging protocol. Although they concluded that FSA is an unreliable tool, it could still avert an unnecessary morbid procedure in almost half of the women.

NCCN recommends radical hysterectomy with SLNB or pelvic lymphnode dissection in early cervical cancer. European society guidelines say that if on frozen section analysis, SLN is negative, then a systematic pelvic lymphadenectomy is recommended . While, FIGO still maintains SLNB to be experimental .

Despite all this international evidence regarding SLNB in cervical cancer, prospective Indian data remains sparse, with just one small study. Hence, we propose to conduct this prospective cohort study to validate the SLNB procedure in cervical cancer, its FSA and ultrastaging in our institute, by testing its diagnostic performance and adding to the existing pool of data.

This prospective cohort pilot study aims to evaluate the diagnostic accuracy of the sentinel lymph node (SLN) mapping algorithm combined with ultra-staging in detecting lymph node metastasis in patients with early-stage cervical cancer, using systematic lymphadenectomy with routine histopathological examination (H&E staining) as the gold standard. After obtaining approval from the Institutional Ethics Committee, 20 consecutive eligible patients with clinical and radiological early-stage cervical cancer planned for primary surgery will be recruited following informed consent. All patients will undergo open surgery with indocyanine green (ICG)-guided SLN mapping involving four-quadrant cervical injections. SLN identification will be performed using near-infrared imaging, followed by the excision of mapped SLNs and any suspicious lymph nodes for frozen section analysis (FSA). If metastasis is detected on FSA, radical hysterectomy will be abandoned, and patients will receive definitive chemoradiotherapy; however, they will continue to be included in the study for analysis. If FSA is negative, systematic bilateral pelvic lymphadenectomy and appropriate hysterectomy (Type B/C ± BSO) will be completed. Histopathological evaluation of SLNs will include frozen section, routine H&E staining, and detailed ultra-staging with additional serial sections and immunohistochemistry (IHC) when required. Non-sentinel pelvic lymph nodes will be evaluated with routine H&E staining. Lymph node metastases will be classified as macro-metastasis, micro-metastasis, or isolated tumor cells. The findings of this study will help determine the diagnostic performance of SLN mapping and ultra-staging as a potential alternative to systematic lymphadenectomy in early-stage cervical cancer

Detailed Description: Not available

Recruitment & Eligibility

Status: Not Yet Recruiting

Sex: Female

Target Recruitment: 20

Inclusion Criteria

To evaluate the SLN detection rates (DR) i.Patient specific ii.Side specific iii.Bilateral 2.
To calculate the sensitivity (Sn), false negative rate (FNR) and negative predictive value (NPV) of SLNM algorithm.

Exclusion Criteria

Inability to understand and/or consent for the procedure 2.
ECOG 2 or more 3.
Locally advanced disease/ enlarged or suspicious lymphnodes/ intrabdominal / distant metastasis on preoperative clinical assessment/ Ultrasonography/ CECT/ MRI pelvis/ chest X ray.
•Locally advanced disease detected intra operatively(bladder/ lateral parametrial/ uterosacral involvement/ intra peritoneal metastasis) •Previous surgeries / procedures impairing lymphatic drainage (myomectomy/ retroperitoneal surgery/ abdominopelvic radiotherapy) •Previous neo-adjuvant therapy – chemotherapy/ radiotherapy.
•Allergy to iodine •Known liver disease •Pre-existing lymphoedema.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
1.To evaluate the SLN detection rates (DR)	after enrollment is completed
i.Patient specific	after enrollment is completed
ii.Side specific	after enrollment is completed
iii.Bilateral	after enrollment is completed
2.To calculate the sensitivity (Sn), false negative rate (FNR) and negative predictive value (NPV) of SLNM algorithm.	after enrollment is completed

Secondary Outcome Measures

Name	Time	Method
-To calculate the sensitivity (Sn), false negative rate (FNR) and negative predictive value (NPV) of sentinel lymph node biopsy (SLNB).	-To calculate the sensitivity (Sn), false negative rate (FNR) and negative predictive value (NPV) of frozen section analysis (FSA) of SLNs.

Trial Locations

Locations (1): Tata Memorial Hospital
🇮🇳
(Suburban), MAHARASHTRA, India
Tata Memorial Hospital
🇮🇳(Suburban), MAHARASHTRA, India
Dr Rohini Kulkarni
Principal investigator
8281376824
dr.rohini.vk@gmail.com