Sentinel Lymph Node Biopsy in Patients With Early Stages Cervical Cancer (SENTIX)

Charles University, Czech Republic

Status: Completed

Conditions: Cervical Cancer

Treatments: Procedure: At least unilateral systematic pelvic lymph node dissection; Procedure: Sentinel lymph node biopsy

Study type: Observational

Funder types: Other

Identifiers

NCT02494063

16-31643A (Other Grant/Funding Number)

ENGOT-Cx 2 (Other Identifier)

Protocol v3.1 (3rd amendment) (Other Identifier)

Protocol v2.0 (1st amendment) (Other Identifier)

CEEGOG CX-01 (Other Identifier)

19-03-00023 (Other Grant/Funding Number)

Protocol v3.0 (2nd amendment) (Other Identifier)

Details and patient eligibility

About

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.

Full description

Patients will be enrolled in the study at the time of surgery planning; at this point, a patient´s consent will be requested if inclusion criteria are fulfilled (histological type, FIGO stage, age, performance status, lymph node clinical status). The following procedures will be provided prior to surgery: clinical staging (MRI or EUS), medical data collection, adverse events assessment, lymphedema assessment, quality of life questionnaire, ECOG performance status, weight and height, standard pre-operative laboratory workup, pregnancy test if clinically indicated.

Surgery should be done within 6 weeks of the imaging study (MRI or expert US). During the surgery, local or distant cancer spread outside of the cervix will be excluded, SLN will be detected, and all SLN will be sent for intra-operative pathologic evaluation. In patients with SLN detection on both sides of the pelvis no other lymph nodes will be removed and they will continue in the study. SLN biopsy will be followed by radical hysterectomy (type B, C1, or C2) or fertility-sparing procedure, according to the pre-operative plan.

Intra-operatively, three groups of patient will be excluded from the SLN study group (though they can be included in the control group):

1. Patients with intra-operative detection of more advanced disease stage (> IB1)
2. Patients with failure to detect SLN bilaterally (either no SLN detected or only on one side of the pelvis)
3. Patients with intra-operative pathologic detection of macrometastases or micrometastases in SLN

In these patients who were excluded from the study group, further surgery and adjuvant treatment will be provided according to the institutional guidelines. These patients will remain in a database and reasons for their exclusion from the SLN study group will be entered into the SIS (Form 2).

A control group will be established to compare postoperative morbidity in patients after SLN biopsy only and after complete pelvic lymphadenectomy. Patients in whom complete lymphadenectomy was performed at least on one side of the pelvis will be eligible for the control group.

In patients, who continue in the study, all SLNs will be processed by pathologists according to the protocol for SLN ultrastaging (Chapter 7.4.2; Appendix 11). If macrometastases or micrometastases or isolated tumor cells are detected in any of the SLNs by pathologic ultrastaging after the surgery, adjuvant radiotherapy will be recommended to the patient. No adjuvant treatment will be offered to those with negative final lymph node status, confirmed pre-operative disease FIGO stage (IA1 - IB1), and adequately performed radical hysterectomy with negative parametrial and vaginal margins.

Follow-up will consist of visits at regular intervals of 6 months after the surgery (additional visits in shorter intervals can be scheduled according to institutional guidelines). The following procedures will be provided at each visit during the follow-up period: pelvic examination, symptomatic lymphocele assessment, quality of life assessment (6 and 12 months after the surgery), adverse events assessment, and secondary lower extremity lymphedema assessment (maximum 6 years after surgery in SLN group, 4 years in Control group). Other imaging studies will be done only if clinically indicated. Any postoperative complication or disease recurrence will be managed according to the institutional guidelines.

Outcomes after fertility sparing procedures in selected centres with be collected (i.e. morbidity after cervical procedure or ovarian transposition, treatment of infertility, pregnancy rates and complications).

Enrollment: 600 patients

Sex: Female

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

I) SLN study group:

Inclusion criteria:

A) Preoperative:

1. FIGO stage IA1+LVSI; IA2; IB1

2. No evidence of bulky or suspicious pelvic lymph nodes or distant metastases in preoperative conventional imaging studies

3. Performance status ECOG: 0 - 1

4. Age ≥ 18 years, ≤ 75 years

5. Squamous cell carcinoma OR Adenocarcinoma usual type (HPV related)

6. 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

7. History of second primary cancer only if > 5 years with no evidence of disease

8. Approved and signed Informed consent

B) Intra-operative

1. Bilateral SLN detection
2. Negative intra-operative pathologic SLN evaluation (frozen section)
3. No intra-operative evidence of more advanced disease (>IB1)

Exclusion Criteria:

1. Neoadjuvant chemotherapy
2. Pregnancy
3. History of pelvic or abdominal radiotherapy
4. HIV positivity / AIDS
5. Adenosquamous cancer or adenocarcinoma unusual type (non HPV related - such as: mucinous, clear cell, mesonephric)

II) Control Group:

Inclusion criteria:

A) Preoperative:

1. FIGO stage IA1 + LVSI; IA2; IB
2. Performance status ECOG: 0-1
3. Age ≥ 18 years, ≤ 75 years
4. Patient is not pregnant
5. No history of pelvic or abdominal radiotherapy
6. Patient scheduled for surgical treatment including systematic pelvic lymphadenectomy
7. Approved and signed Informed Consent

B) Intra-operative:

a) Systematic pelvic lymphadenectomy performed at least on one side of the pelvis

Exclusion criteria:

1. Pregnancy
2. History of pelvic or abdominal radiotherapy

Trial design

600 participants in 2 patient groups

Sentinel lymph node (SLN)

Description:

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

Treatment:

Procedure: Sentinel lymph node biopsy

Control

Description:

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.

Treatment:

Procedure: At least unilateral systematic pelvic lymph node dissection