Uterine Manipulator Versus no Uterine Manipulator in Endometrial Cancer Trial

Official title

Randomized Controlled Trial on the Oncologic Outcomes of Use Versus Not Use of the Uterine Manipulator in the Surgical Treatment of Apparent Uterine-confined Endometrial Carcinoma

Overview

Minimally invasive surgery is the recommended approach in endometrial cancer (EC) patients based on the results of two randomized controlled trials, given its advantages without compromised oncologic outcomes. The uterine manipulator is commonly used in benign and malignant pathologies to perform a laparoscopic or robotic hysterectomy. However, although regularly used, the uterine manipulator adoption in EC is a controversial technical aspect due to the raised concerns regarding the possible risk of disruption of the tumor mass, the spread of malignant cells, and seeding of the disease, particularly at the level of the vaginal cuff or spread of tumor cells, with increased risk of recurrence and death due to EC. On that basis, given that hysterectomy without a uterine manipulator is feasible, only a randomized controlled trial comparing oncologic outcomes in EC patients after use versus not use of the uterine manipulator will be able to provide high-quality evidence to answer this critical question and allow or exclude the use of a uterine manipulator during minimally invasive hysterectomy for EC.

Interventions

• Device Uterine manipulator use
  The uterine manipulator will be inserted into the uterus to assist in the procedure of total hysterectomy.

Primary outcome measures

• Recurrence-free survival [Time frame: Each follow-up visit, up to 4 years from the day of surgery]

Secondary outcome measures (9)

• Cause-specific survival [Time frame: Each follow-up visit, up to 4 years from the day of surgery]
• Overall survival [Time frame: Each follow-up visit, up to 4 years from the day of surgery]
• Site-specific recurrence-free survival [Time frame: Each follow-up visit, up to 4 years from the day of surgery]
• Operative time [Time frame: Day of surgery]
• Intraoperative blood loss [Time frame: Day of surgery]
• 30-day post-surgical morbidity [Time frame: 30 days after surgery]
• Lymphovascular space invasion [Time frame: Day of surgery]
• Peritoneal cytology [Time frame: Day of surgery]
• Quality of life indexes [Time frame: Each follow-up visit, up to 4 years from the day of surgery]

Eligibility criteria

Inclusion criteria

• Diagnosis of Endometrial Cancer of any histology (including carcinosarcoma) and grade
• Planned surgical treatment including hysterectomy and bilateral salpingo-oophorectomy (ovarian preservation in selected patients is not an exclusion criterion)
• Age ≥ 18 years
• No preoperative evidence of extrauterine disease (Clinical stage IIIA, IIIB)
• No preoperative evidence of suspicious lymph nodes (Clinical stage IIIC)
• No preoperative evidence of distant metastasis (Clinical stage IV)
• Approved and signed informed consent

Exclusion criteria

• Neoadjuvant therapy
• Synchronous or previous (< 5 years) invasive cancer, not including non-melanoma skin cancer
• Fertility preservation
• World Health Organization performance score > 2
• Uterine sarcoma
• Previous pelvic/abdominal radiotherapy, hormone therapy for cancer (< 5 years), chemotherapy (< 5 years), pelvic or paraaortic lymphadenectomy, or retroperitoneal surgery
• Inadequate bone marrow function (white blood cells <3·0×109/L, platelets <100×109/L)
• Inadequate liver function (bilirubin >1.5×upper normal limit \[UNL\], aspartate aminotransferase, and alanine aminotransferase >2.5 × UNL)
• Inadequate kidney function (creatinine clearance < 60 mL per min calculated according to Cockcroft-Gault 10 or < 50 mL per min Ethylenediaminetetraacetic acid clearance)
• Intraoperative evidence of stage IV disease

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Italy · 3 centers

• UOC Ostetricia e Ginecologia, Azienda Ospedaliera Santa Croce e Carle — Cuneo
• UOC Ostetricia e Ginecologia, Arcispedale Santa Maria Nuova — Reggio Emilia
• AOUI Verona - University of Verona - Department of Obstetrics and Gynecology — Verona

Publications

• Concin N, Matias-Guiu X, Vergote I, Cibula D, Mirza MR, Marnitz S, Ledermann J, Bosse T, Chargari C, Fagotti A, Fotopoulou C, Gonzalez Martin A, Lax S, Lorusso D, Marth C, Morice P, Nout RA, O'Donnell D, Querleu D, Raspollini MR, Sehouli J, Sturdza A, Taylor A, Westermann A, Wimberger P, Colombo N, Planchamp F, Creutzberg CL. ESGO/ESTRO/ESP guidelines for the management of patients with endometria PMID 33397713
• van den Haak L, Alleblas C, Nieboer TE, Rhemrev JP, Jansen FW. Efficacy and safety of uterine manipulators in laparoscopic surgery: a review. Arch Gynecol Obstet. 2015 Nov;292(5):1003-11. doi: 10.1007/s00404-015-3727-9. Epub 2015 May 13. PMID 25967852
• Uccella S, Cianci S, Gueli Alletti S. Uterine manipulator in endometrial cancer: we are still far from the answer. Am J Obstet Gynecol. 2021 Mar;224(3):332. doi: 10.1016/j.ajog.2020.09.049. Epub 2020 Nov 15. No abstract available. PMID 33207238
• Uccella S, Bonzini M, Malzoni M, Fanfani F, Palomba S, Aletti G, Corrado G, Ceccaroni M, Seracchioli R, Shakir F, Ferrero A, Berretta R, Tinelli R, Vizza E, Roviglione G, Casarella L, Volpi E, Cicinelli E, Scambia G, Ghezzi F. The effect of a uterine manipulator on the recurrence and mortality of endometrial cancer: a multi-centric study by the Italian Society of Gynecological Endoscopy. Am J Obst PMID 28147240
• Padilla-Iserte P, Lago V, Tauste C, Diaz-Feijoo B, Gil-Moreno A, Oliver R, Coronado P, Martin-Salamanca MB, Pantoja-Garrido M, Marcos-Sanmartin J, Gilabert-Estelles J, Lorenzo C, Cazorla E, Roldan-Rivas F, Rodriguez-Hernandez JR, Sanchez L, Muruzabal JC, Hervas D, Domingo S; Spanish Society of Gynecology and Obstetrics Spanish Investigational Network Gynecologic Oncology Group. Impact of uterine m PMID 32693096
• Uccella S, Puppo A, Ghezzi F, Zorzato PC, Ceccaroni M, Mandato VD, Berretta R, Camanni M, Seracchioli R, Perrone AM, Chiantera V, Vizzielli G, Sozzi G, Beretta P, Steinkasserer M, Legge F, Stevenazzi G, Candotti G, Bergamini V, Fanfani F, Garzon S. A randomized controlled trial on the oncologic outcomes of use of the intrauterine manipulator in the treatment of apparent uterine-confined endometria PMID 39266205

Identifiers

NCT: NCT05687084 · MANEC Trial

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗