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).

Centre Hospitalier Universitaire de Quebec Department of Obstetrics and Gynecology Quebec QC Canada

Charles University and General University Hospital Prague 1st Faculty of Medicine Department of Gynaecology Obstetrics and Neonatology Gynecologic Oncology Centre Prague Czech Republic

Clinica Universidad de Navarra Departamento de Ginecologia y Obstetricia Pamplona Spain

Facility of Epidemiology and Biostatistics Policlinico Universitario A Gemelli IRCCS Rome Italy

Houston Methodist Hospital Neal Cancer Center Department of Obstetrics and Gynecology Houston TX USA

Imperial College London Faculty of Medicine Department of Gynaecological Oncology London London UK

Institut Curie Department of Breast and Gynaecological Surgery Paris France

Institut Universitaire du Cancer Toulouse Oncopole Institut Claudius Regaud Surgical Oncology Department Toulouse France

Karolinska Institutet Department of Women's and Children's Health Karolinska University Hospital Department of Gynecological Cancer Stockholm Sweden

Memorial Sloan Kettering Cancer Center Department of Surgery New York NY USA

UOC Ginecologia Oncologica Dipartimento di Scienze della Salute della Donna del Bambino e di Sanità Pubblica Fondazione Policlinico Universitario A Gemelli IRCCS Rome Italy

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ClinicalTrials.gov
NCT06416748