Clinical trial NCT04570553: Use of an Intrauterine Manipulator and Its Correlation with Positive Peritoneal Cytology in Early Stage Endometrial Cancers
Official title: Use of an Intrauterine Manipulator and Its Correlation with Positive Peritoneal Cytology in Early Stage Endometrial Cancers
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Endometrial Cancer
Keywords: endometrial cancer
peritoneal cytology
Lead sponsor: WellSpan Health
Sponsor class: OTHER
First posted: 2020-09-30
Enrollment: 350
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Subjects are randomized to one of two groups in parallel: V-care uterine manipulator group or sponge stick group
Primary purpose: DIAGNOSTIC

Brief summary: This study aims to answer whether use of a Vcare® intrauterine manipulator leads to an increased incidence of positive peritoneal cytology in patients undergoing surgical management of early stage (FIGO stage I/II) endometrial cancer.

Detailed description: Endometrial cancer is the sixth most common cancer diagnosed in women worldwide and the leading gynecologic cancer in developed countries, accounting for nearly 50% of all newly diagnosed gynecologic cancers in the United States . The majority of endometrial cancers are diagnosed at an early stage which portends a favorable prognosis. Despite early diagnosis and generally favorable prognosis in these cancers, approximately 13% of patients will experience recurrence . Most recurrences occur in patients with known high-risk pathologic features, however approximately 3% of recurrences occur in patients with no high-risk pathology features . While well-defined pathologic factors such as age, tumor grade, and depth of invasion have been described for high-risk of recurrence, predicting recurrence in low-risk patients has been an ongoing challenge in the management of early stage endometrial cancers

One potential contribution to recurrence in low-risk endometrial cancers may be the presence of positively malignant peritoneal cytology. Positive peritoneal cytology (PPC) has been an ongoing topic of debate regarding its significance and optimal management in early stage endometrial cancers. Creasman and Rutledge initially described the prognostic value of peritoneal cytology in 1971 by linking PPC with worse survival at 4 years . Since then multiple studies have sought to address the significance of peritoneal cytology in endometrial cancer, many with conflicting results. Studies by Kasamatsu et al, Fadare et al, Lurain et al and Scott et al found that PPC is not a significant prognostic factor for disease recurrence or survival . Contrary to these data however studies by Lee et al, Garg et al, and Seagle et al have shown a positive correlation with PPC as both a prognostic factor and survival . Despite these conflicting data directing the significance of PPC, it remains an important contributing factor in the management and prognosis of endometrial cancer. Although peritoneal cytology was removed from FIGO staging in 2009, NCCN guidelines continue to recommend the collection of peritoneal cytology in order to further elucidate the impact of PPC, with some authors calling for the reinstatement of peritoneal cytology in endometrial cancer staging .

In addition to the effects of pathological factors and peritoneal cytology on recurrence risk, recent studies in other gynecologic cancers have shown how different approaches in surgical management play a key role in overall disease prognosis and outcomes. The LACC trial, published in 2018, demonstrated the effects of differing surgical technique on outcomes by showing that patients undergoing minimally invasive surgery for management of cervical cancers fared worse in locoregional recurrence, disease-free survival and overall survival than patients undergoing traditional laparotomy. This study highlights the impact of surgical methodology on the prognosis and outcomes of oncologic surgery.

Similar to the management of cervical cancers, over the last two decades laparoscopic surgery and staging has become the mainstay of management for women with uterine cancers. The traditional approach of laparotomy with hysterectomy, bilateral salpingo-oophorectomy, pelvic and para-aortic lymphadenectomy has come to be effectively replaced with the minimally invasive, laparoscopic approach which affords an equally efficacious surgery with shorter recovery and fewer complications . In order to perform more efficient and safe surgeries, intrauterine manipulators have been employed in laparoscopic hysterectomy. Since their introduction into gynecologic oncology surgery questions have risen regarding the possibility of increased risk of tumor dissemination with usage of intrauterine manipulators. The mechanisms of this have been theorized to include retrograde dissemination via the fallopian tubes into the peritoneal cavity as well as increased lymphovascular space invasion . Multiple studies have focused on the question of retrograde dissemination via the fallopian tubes with conflicting results. A retrospective study by Sonoda et el found that when low-risk endometrial cancer was managed with laparoscopic assisted vaginal hysterectomy (LAVH) using an inflatable intrauterine manipulator, it was associated with increased incidence of positive peritoneal cytology compared to the control population (10.3% versus 2.8%). Lim et al prospectively evaluated the effect of uterine manipulator use on peritoneal cytology in laparoscopic hysterectomy using a RUMI manipulator and KOH colpotomizer and found that 4.3% of patients in their study were upstaged due to PPC following usage of a uterine manipulator . However, contrary to this, two prospective studies found that usage of a uterine manipulator did not increase the incidence of malignant peritoneal cytology in patients undergoing laparoscopic staging. A prospective study by Eltabakh et al evaluated conversion from negative to PPC immediately following insertion of a Pelosi uterine manipulator in 42 patients. Based on their results that demonstrated no patients converted to PPC, they concluded that intrauterine manipulators do not increase the incidence of PPC. Additionally, Lee et al published results of a randomized parallel trial of 110 patients undergoing laparoscopic surgery and staging for stage I endometrial cancer either with or without a uterine manipulator which showed no significant difference in the rate of positive cytology in either group.

This study will be a randomized control trial in which patients will be randomized into two study arms following informed consent: a control arm utilizing a non-invasive sponge stick (Foerster ring forceps containing a raytec sponge (Vistec Covidien Health, Mansfield, MA)) placed in the vagina for surgical assistance or a Vcare® intrauterine manipulator (ConMed Endosurgery, Utica, NY). Patients randomized to the Vcare® group will have the Vcare® placed in the usual fashion under direct visualization following entrance into the abdomen. Cytology washings will be obtained following entrance into the peritoneal cavity. Washings will be obtained by washing approximately 150cc of normal saline over the bilateral paracolic gutters, uterine fundus, and anterior and posterior cul de sacs. Fifty milliliters of fluid will then be aspirated for cytology collection. Cytology washings will then be obtained again prior to colpotomy. Patients will undergo total laparoscopic hysterectomy or robotic assisted total laparoscopic hysterectomy. Peritoneal washings obtained during surgery will be processed and undergo pathological examination. Covariate data including age, BMI, history of previous tubal ligation, FIGO stage, histologic type, histologic grade, lymphovascular space invasion, and gross evidence of tumor spillage will also be obtained.

Eligibility criteria: Inclusion Criteria:

* Subjects age 18 or older able to give informed consent
* Biopsy diagnosed endometrial cancer (including endometrioid, serous, mucinous and clear cell histologies)
* Planned standard of care surgical management of early stage endometrial cancer
* No clinical evidence of disseminated intraperitoneal disease

Exclusion Criteria:

* Final pathology does not reflect diagnosis of endometrial cancer (including endometrioid, serous, mucinous, and clear cell histology)
* Evidence of disseminated intraperitoneal disease
* Subject is not a surgical candidate
* Subject elects for fertility sparing or non-operative management
* Subject is unable to provide informed consent

Primary outcomes:
measure: Conversion of positive peritoneal cytology
timeFrame: 2 years
Secondary outcomes:
measure: Recurrence rate
timeFrame: 2 years
Other outcomes:
Locations:
city: York
country: United States
facility: Wellspan Health
state: Pennsylvania
Study officials:
affiliation: WellSpan Health
name: Eav Lim, DO
role: PRINCIPAL_INVESTIGATOR
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