Minimally invasive simple hysterectomy in low-risk cervical cancer: a single-arm trial with stopping rules (ENGOT-cx23/MITO/LASH trial).

Abstract

Background: The oncologic safety of minimally invasive simple hysterectomy in low-risk cervical cancer has not been explored by an adequately powered clinical trial.

Primary objective: This study aims to evaluate whether minimally invasive simple hysterectomy affects disease-free survival in low-risk early-stage cervical cancer.

Study hypothesis: Minimally invasive simple hysterectomy represents an oncologically safe approach in selected patients with low-risk cervical cancer.

Trial design: This is a single-arm trial with stopping rules. All patients must undergo cervical conization. Patients with clear conization margins or absence of residual macroscopic disease at imaging after conization (re-conization is mandatory if these criteria are not met) are submitted to minimally invasive (laparoscopy or robot-assisted laparoscopy) simple hysterectomy with sentinel lymph node biopsy algorithm. Adjuvant therapy is given in case of tumor-involved surgical margins, and/or metastatic lymph nodes, and/or substantial lymphovascular space invasion with depth of stromal infiltration >2/3 (or tumor-free distance ≤3 mm).

Major inclusion/exclusion criteria: The major inclusion criteria are: squamous cell carcinoma, human papillomavirus-related adenocarcinoma, adenosquamous carcinoma of the uterine cervix; International Federation of Gynecology and Obstetrics 2018 stage IA2-IB1 (≤2 cm) with depth of infiltration ≤10 mm on conization specimen; International Federation of Gynecology and Obstetrics 2018 stage IA2-IB1 (≤2 cm) with depth of infiltration ≤50% at pre-conization magnetic resonance imaging scan or "expert" ultrasound scan. Women are not eligible if they have evidence of metastatic disease, contra-indications to surgery and/or lymph node assessment, or fertility sparing desire.

Primary endpoint: The primary end point is 3-year disease-free survival of patients who undergo minimally invasive simple hysterectomy.

Sample size: A sample size of 974 patients will give a power of 80% at a significance level of 2.5% (1-sided) to reject the null hypothesis of a 3-year recurrence rate of 2.4%, assuming a 3-year recurrence rate of 1.2%. A maximum of 14 recurrences at 3 years should be observed to reject the null hypothesis. A stopping rule based on the number of recurrences observed at different timepoints will be implemented to avoid a higher recurrence rate with the study procedure. The trial will also be stopped if no recurrences are observed in the first 400 patients followed up for 2 years.

Estimated dates for completing accrual and presenting results: The enrolment will last 60 months. After the surgery, the follow-up time will be ≥3 years.

Trial registration: The trial is registered at ClinicalTrials.gov (NCT06416748) and as ENGOT/MITO trial (ENGOT-cx23).