Sentinel Lymph Node Biopsy in Patients With Early Stages Cervical Cancer

NCT02494063 | Completed DMC

• 7 other identifiers: CEEGOG CX-01ENGOT-Cx 2Protocol v2.0 (1st amendment)Protocol v3.0 (2nd amendment)Protocol v3.1 (3rd amendment)16-31643A19-03-00023
• Study Type: observational
• Target: 600
• Locations: 1 country
• Sites: 1

Brief Summary

To evaluate whether a less radical surgical approach with sentinel lymph node biopsy is non-inferior to treatment with systematic pelvic lymphadenectomy. The null hypothesis is that the recurrence rate after SLN biopsy is non-inferior to the reference recurrence rate of 7 % (at the 24th month of follow-up) in patients after systematic pelvic lymphadenectomy, but that the less radical surgery is associated with significantly lower postoperative morbidity.

Conditions

Cervical Cancer

Keywords

cervical cancer; sentinel lymph node; lymphadenectomy

Outcome Measures

Primary Outcomes (1)

• Recurrence rate at the 24th month of follow-up (cervical recurrences after fertility-sparing procedures will be excluded)

  Recurrence rate (RR) will be estimated at the 24th month of follow-up to prove a non-inferiority of SLN biopsy to the reference value (RR 24th month: 7 %).

  24 months

Secondary Outcomes (11)

• Prevalence of symptomatic pelvic lymphocele

  2 years

• Prevalence of lower extremity lymphedema

  2 years

• Postoperative morbidity

  2 years

• DFS (Disease-free survival)

  2 years

• Pelvic DFS (Pelvic Disease-free survival)

  2 years

Study Arms (2)

Sentinel lymph node (SLN)

Only sentinel lymph node biopsy, no further pelvic lymph nodes removal, radical hysterectomy.

Procedure: Sentinel lymph node biopsy

Control

Control group is composed by either those who were enrolled into the trial, but who did not fulfil intra-operative criteria (especially failure to detect SLN on both pelvic side walls) or those in whom systematic lymphadenectomy is planned upfront.

Procedure: At least unilateral systematic pelvic lymph node dissection

Interventions

Sentinel lymph node biopsy PROCEDURE

Bilateral sentinel lymph node biopsy, pathologic ultrastaging

Sentinel lymph node (SLN)

At least unilateral systematic pelvic lymph node dissection PROCEDURE

Control

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with early stages cervical cancer

You may qualify if:

• A) Preoperative:
• FIGO stage IA1+LVSI; IA2; IB1
• No evidence of bulky or suspicious pelvic lymph nodes or distant metastases in preoperative conventional imaging studies
• Performance status ECOG: 0 - 1
• Age ≥ 18 years, ≤ 75 years
• Squamous cell carcinoma OR Adenocarcinoma usual type (HPV related)
• Suitable candidates for primary surgical treatment such as:
• radical hysterectomy in tumors ≤ 4 cm in the largest diameter OR
• fertility-sparing treatment in tumors ≤ 2 cm in the largest diameter
• History of second primary cancer only if \> 5 years with no evidence of disease
• Approved and signed Informed consent
• B) Intra-operative
• Bilateral SLN detection
• Negative intra-operative pathologic SLN evaluation (frozen section)
• No intra-operative evidence of more advanced disease (\>IB1)

You may not qualify if:

• Neoadjuvant chemotherapy
• Pregnancy
• History of pelvic or abdominal radiotherapy
• HIV positivity / AIDS
• Adenosquamous cancer or adenocarcinoma unusual type (non HPV related - such as: mucinous, clear cell, mesonephric)
• II) Control Group:
• A) Preoperative:
• FIGO stage IA1 + LVSI; IA2; IB
• Performance status ECOG: 0-1
• Age ≥ 18 years, ≤ 75 years
• Patient is not pregnant
• No history of pelvic or abdominal radiotherapy
• Patient scheduled for surgical treatment including systematic pelvic lymphadenectomy
• Approved and signed Informed Consent
• B) Intra-operative:

Sponsors & Collaborators

• Charles University, Czech Republic: lead

Study Sites (1)

Gynecologic Oncology Center in Prague

Prague, 15000, Czechia

Location

Related Publications (15)

• Zikan M, Fischerova D, Pinkavova I, Slama J, Weinberger V, Dusek L, Cibula D. A prospective study examining the incidence of asymptomatic and symptomatic lymphoceles following lymphadenectomy in patients with gynecological cancer. Gynecol Oncol. 2015 May;137(2):291-8. doi: 10.1016/j.ygyno.2015.02.016. Epub 2015 Feb 24.

  PMID: 25720294 BACKGROUND

• Cibula D, Oonk MH, Abu-Rustum NR. Sentinel lymph node biopsy in the management of gynecologic cancer. Curr Opin Obstet Gynecol. 2015 Feb;27(1):66-72. doi: 10.1097/GCO.0000000000000133.

  PMID: 25502426 BACKGROUND

• Giammarile F, Bozkurt MF, Cibula D, Pahisa J, Oyen WJ, Paredes P, Olmos RV, Sicart SV. The EANM clinical and technical guidelines for lymphoscintigraphy and sentinel node localization in gynaecological cancers. Eur J Nucl Med Mol Imaging. 2014 Jul;41(7):1463-77. doi: 10.1007/s00259-014-2732-8. Epub 2014 Mar 8.

  PMID: 24609929 BACKGROUND

• Cibula D, Abu-Rustum NR, Dusek L, Slama J, Zikan M, Zaal A, Sevcik L, Kenter G, Querleu D, Jach R, Bats AS, Dyduch G, Graf P, Klat J, Meijer CJ, Mery E, Verheijen R, Zweemer RP. Bilateral ultrastaging of sentinel lymph node in cervical cancer: Lowering the false-negative rate and improving the detection of micrometastasis. Gynecol Oncol. 2012 Dec;127(3):462-6. doi: 10.1016/j.ygyno.2012.08.035. Epub 2012 Aug 31.

  PMID: 22943880 BACKGROUND

• Cibula D, Abu-Rustum NR, Dusek L, Zikan M, Zaal A, Sevcik L, Kenter GG, Querleu D, Jach R, Bats AS, Dyduch G, Graf P, Klat J, Lacheta J, Meijer CJ, Mery E, Verheijen R, Zweemer RP. Prognostic significance of low volume sentinel lymph node disease in early-stage cervical cancer. Gynecol Oncol. 2012 Mar;124(3):496-501. doi: 10.1016/j.ygyno.2011.11.037. Epub 2011 Nov 25.

  PMID: 22120175 BACKGROUND

• Cibula D, Abu-Rustum NR, Benedetti-Panici P, Kohler C, Raspagliesi F, Querleu D, Morrow CP. New classification system of radical hysterectomy: emphasis on a three-dimensional anatomic template for parametrial resection. Gynecol Oncol. 2011 Aug;122(2):264-8. doi: 10.1016/j.ygyno.2011.04.029. Epub 2011 May 17.

  PMID: 21592548 BACKGROUND

• Cibula D, Abu-Rustum NR. Pelvic lymphadenectomy in cervical cancer--surgical anatomy and proposal for a new classification system. Gynecol Oncol. 2010 Jan;116(1):33-7. doi: 10.1016/j.ygyno.2009.09.003. Epub 2009 Oct 17.

  PMID: 19837449 BACKGROUND

• Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004 Aug;240(2):205-13. doi: 10.1097/01.sla.0000133083.54934.ae.

  PMID: 15273542 BACKGROUND

• Cibula D, Marnitz S, Jarkovsky J, Kocian R, Dundr P, Klat J, Zapardiel I, Arencibia O, Landoni F, Presl J, Raspagliesi F, Zikan M, van Lonkhuijzen LR, Torne A, Slama J, Minar L, Ostojich M, Pilka R, Petiz AF, Petzel A, Burgetova A, Fischerova D, Nemejcova K, Kohler C. 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. Nat Cancer. 2025 Sep;6(9):1585-1594. doi: 10.1038/s43018-025-01016-y. Epub 2025 Jul 4.

  PMID: 40615729 DERIVED

• Borcinova M, Kohler C, Nemejcova K, Zapardiel I, Klat J, Fruhauf F, Kalist V, Szatkowski W, Wydra D, Kocian R, Laky R, Toth R, Misiek M, Redecha M, Martin I, Kridelka F, Burgetova A, Santiago Garcia FJ, Van Gorp T, Szewczyk G, Kipp B, Poka R, Coronado PJ, Cadron I, Luyckx M, Fischerova D, Fischbach R, Cibula D. Preoperative tumour size assessment in patients with early-stage cervical cancer: Final results of the SENTIX study. Gynecol Oncol. 2025 May;196:160-167. doi: 10.1016/j.ygyno.2025.04.005. Epub 2025 Apr 11.

  PMID: 40220456 DERIVED

• Cibula D, Kohler C, Jarkovsky J, Kocian R, Dundr P, Klat J, Zapardiel I, Landoni F, Fruhauf F, Fischbach R, Borcinova M, Fischerova D. Magnetic resonance imaging and ultrasound examination in preoperative pelvic staging of early-stage cervical cancer: post-hoc analysis of SENTIX study. Ultrasound Obstet Gynecol. 2025 Apr;65(4):495-502. doi: 10.1002/uog.29205. Epub 2025 Mar 25.

  PMID: 40130299 DERIVED

• Kocian R, Kohler C, Bajsova S, Jarkovsky J, Zapardiel I, Di Martino G, van Lonkhuijzen L, Sehnal B, Sanchez OA, Gil-Ibanez B, Martinelli F, Presl J, Minar L, Pilka R, Kascak P, Havelka P, Michal M, van Gorp T, Nemejcova K, Dundr P, Cibula D. Sentinel lymph node pathological ultrastaging: Final outcome of the Sentix prospective international study in patients with early-stage cervical cancer. Gynecol Oncol. 2024 Sep;188:83-89. doi: 10.1016/j.ygyno.2024.06.015. Epub 2024 Jun 27.

  PMID: 38941963 DERIVED

• Borcinova M, Ragosch V, Jarkovsky J, Bajsova S, Pilka R, Glickman A, Garrido-Mallach S, Raspagliesi F, Szatkowski W, Pakiz M, Snyman LC, Kocian R, Tamussino K, Kalist V, Michal M, Segovia MG, Poka R, Kipp B, Szewczyk G, Wydra D, Toth R, Vinnytska A, Fischerova D, Siegler K, Cibula D. Challenges in lower limb lymphoedema assessment based on limb volume change: Lessons learnt from the SENTIX prospective multicentre study. Gynecol Oncol. 2022 Jan;164(1):76-84. doi: 10.1016/j.ygyno.2021.10.089. Epub 2021 Nov 8.

  PMID: 34763939 DERIVED

• Cibula D, Kocian R, Plaikner A, Jarkovsky J, Klat J, Zapardiel I, Pilka R, Torne A, Sehnal B, Ostojich M, Petiz A, Sanchez OA, Presl J, Buda A, Raspagliesi F, Kascak P, van Lonkhuijzen L, Barahona M, Minar L, Blecharz P, Pakiz M, Wydra D, Snyman LC, Zalewski K, Zorrero C, Havelka P, Redecha M, Vinnytska A, Vergote I, Tingulstad S, Michal M, Kipp B, Slama J, Marnitz S, Bajsova S, Hernandez A, Fischerova D, Nemejcova K, Kohler C. Sentinel lymph node mapping and intraoperative assessment in a prospective, international, multicentre, observational trial of patients with cervical cancer: The SENTIX trial. Eur J Cancer. 2020 Sep;137:69-80. doi: 10.1016/j.ejca.2020.06.034. Epub 2020 Aug 1.

  PMID: 32750501 DERIVED

• Cibula D, Dusek J, Jarkovsky J, Dundr P, Querleu D, van der Zee A, Kucukmetin A, Kocian R. A prospective multicenter trial on sentinel lymph node biopsy in patients with early-stage cervical cancer (SENTIX). Int J Gynecol Cancer. 2019 Jan;29(1):212-215. doi: 10.1136/ijgc-2018-000010.

  PMID: 30640706 DERIVED

MeSH Terms

Conditions

Uterine Cervical Neoplasms

Interventions

Sentinel Lymph Node Biopsy

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Intervention Hierarchy (Ancestors)

Biopsy; Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Lymph Node Excision; Investigative Techniques

Study Officials

• David Cibula, MD

  Gynecologic Oncology Center, Department of Obstetrics and Gynecology, General University Hospital and 1st Faculty of Medicine, Charles University Prague, Czechia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 7 Years
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD, Professor

Study Record Dates

• First Submitted: July 6, 2015
• First Posted: July 10, 2015
• Study Start: June 1, 2016
• Primary Completion: December 1, 2022
• Study Completion: February 1, 2024
• Last Updated: February 8, 2024

Record last verified: 2024-02

Locations

CZ (1)