Clinical trial NCT02494063: Sentinel Lymph Node Biopsy in Patients With Early Stages Cervical Cancer
Official title: A Prospective Observational Trial on Sentinel Lymph Node Biopsy in Patients With Early Stage Cervical Cancer
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Cervical Cancer
Keywords: cervical cancer
sentinel lymph node
lymphadenectomy
Lead sponsor: Charles University, Czech Republic
Sponsor class: OTHER
First posted: 2015-07-10
Enrollment: 600
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with early stages cervical cancer

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.

Detailed 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).

Eligibility 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

Primary outcomes:
measure: Recurrence rate at the 24th month of follow-up (cervical recurrences after fertility-sparing procedures will be excluded)
timeFrame: 24 months
Secondary outcomes:
measure: Prevalence of symptomatic pelvic lymphocele
timeFrame: 2 years
measure: Prevalence of lower extremity lymphedema
timeFrame: 2 years
measure: Postoperative morbidity
timeFrame: 2 years
measure: DFS (Disease-free survival)
timeFrame: 2 years
measure: Pelvic DFS (Pelvic Disease-free survival)
timeFrame: 2 years
measure: Quality of life (QoL)
timeFrame: 1 year
measure: Intra-operative morbidity
timeFrame: 1 month
measure: FNR (False Negative Rate) of intra-operative pathologic SLN evaluation
timeFrame: 2 years
measure: DFS in SLN negative patients
timeFrame: 2 years
measure: Recurrence rate safety margins
timeFrame: 2 years
measure: Overall survival
timeFrame: 2 years
Other outcomes:
Locations:
city: Prague
country: Czechia
facility: Gynecologic Oncology Center in Prague
Study officials:
affiliation: Gynecologic Oncology Center, Department of Obstetrics and Gynecology, General University Hospital and 1st Faculty of Medicine, Charles University Prague, Czechia
name: David Cibula, MD
role: PRINCIPAL_INVESTIGATOR
References:
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citation: 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.
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