Opportunistic Salpingectomy During Bariatric Surgery for Ovarian Cancer Prevention

Ovarian cancer is a devastating diagnosis, with high-grade serous cancer (HGSC) accounting for ~70% of ovarian cancers and 90% of deaths from ovarian cancer. HGSC contributes to a low 5-year survival rate of 34%, and 80% of cases occur in average risk patients. Without effective screening methods for HGSC and with treatment innovations not resulting in meaningful survival improvements, prevention is our most powerful tool for reducing morbidity and mortality.

Opportunistic bilateral salpingectomy (OBS) has emerged as the primary prevention strategy for HGSC in average risk individuals who have completed or do not desire childbearing. OBS involves removal of the fallopian tubes at the time of another abdominopelvic surgery, historically hysterectomy or tubal sterilization. This intervention is based on compelling evidence that most HGSCs originate in the fallopian tube epithelium and not the ovary itself. Large population level studies have shown that OBS is effective at reducing the risk of HGSC by around 80%. Substantial evidence also supports the safety of OBS; OBS is not associated with increased perioperative adverse outcomes, including hospital readmission, blood transfusion, longer hospital stay, or minor complications. Multiple studies have also found no adverse effects on ovarian function or onset of menopause. For these reasons, OBS at time of hysterectomy or tubal sterilization is now recommended as standard of practice by 13+ gynecological societies worldwide.

Most research on OBS has been focused on gynecologic surgery, however, many eligible patients undergoing abdominal or pelvic surgery for nongynecologic reasons may benefit. A study examining the preventive potential of offering OBS more widely identified that in patients diagnosed with HGSC, 37% of patients eligible for OBS had a missed surgical opportunity during nongynecologic procedures, usually in general surgery (cholecystectomy, hernia repair, bowel surgery). Several modeling studies have concluded that expanding OBS into common elective general surgery procedures is significantly cost-saving overall. Patient acceptance towards OBS at time of nongynecological surgery has also been shown to be high, with one study demonstrating that 95% of patients would consider it at the time of laparoscopic cholecystectomy (LC). If OBS reduces risk for HGSC by 80%, this suggests that offering patients OBS during general surgery cases as well as gynecological surgeries could save at least 20% of lives lost to ovarian cancer. No new treatments have provided such a significant improvement in survival for HGSC patients over the past 50 years. This has led to a shift in society recommendations to begin expanding criteria for OBS to include individuals undergoing any elective abdominopelvic surgery.

Despite the wide body of evidence supporting OBS, there has been reluctance from general surgeons to begin performing OBS outside of the context of a research study as voiced to a member of this research team, who has been working with the Shared Services Committee of Doctors of BC on a campaign to educate general surgeons about OBS. Additionally, a 2024 survey of Canadian general surgeons and urologists on OBS during nongynecological surgery highlighted a lack of knowledge and comfort. Only 43.7% were aware of current OBS recommendations and only 19.3% had performed OBS at time of appropriate elective surgery. One of the main barriers identified by 51% of respondents in this survey was technical factors in performing OBS. This highlights the ongoing need for further studies supporting OBS in nongynecologic procedures.

Studies investigating the feasibility of implementing OBS in general surgery procedures have shown encouraging results thus far. There has been one multicentre study of patients who underwent elective LC with OBS matched to historical controls. The procedure was successfully completed in 93.3% of patients with no intraoperative or postoperative complications and median additional operating room (OR) time of 13 minutes. A clinical trial on the feasibility and safety of OBS during colorectal surgery is currently underway and completed recruitment, led by one of the research team members. Preliminary results demonstrate that 81% of patients elected to have OBS at the time of their surgery with an 87% success rate, no differences in perioperative adverse outcomes and a mean additional OR time of 3.43 minutes.

Metabolic and bariatric surgery (MBS) represents another high-volume elective abdominal surgery with a large patient population that may benefit from OBS. In Ontario, 82% of patients undergoing MBS are female, with a mean age of 44 (26). Considering 45 years of age as a surrogate for end of fertility, 40% of bariatric surgery patients are potentially eligible for OBS. OBS at time of MBS is seldom offered, likely for similar reasons to those highlighted in the survey of Canadian surgeons previously mentioned. In MBS, there may be added technical concerns with adding a pelvic component to an upper gastrointestinal procedure, as well as unique challenges related to the increased body habitus of bariatric patients (exposure, ports, positioning, etc.).

As public awareness for OBS is increasing, one of the research team members noted that patients have begun expressing interest in OBS at the time of MBS independently. Two abstracts have reported on the feasibility of OBS in this population; one study of 19 patients showed this was 95% feasible with no complications and 8.1 minutes of additional OR time, while another of 31 patients investigated the identification of fallopian tubes during MBS, showing 84% visualization. Thus far, there have been no published, complete studies looking at OBS at time of elective MBS.

The primary aim of our study will be to understand the feasibility of OBS at the time of MBS by measuring how many patients successfully undergo removal of both fallopian tubes at the time of MBS. Secondary outcomes will include the safety and health system consequences of OBS at the time of MBS by reporting on perioperative complications and additional resources required. The results of this study may help fuel widespread implementation of OBS into MBS. As MBS in Ontario is organized into the Ontario Bariatric Network (OBN), the results of this study could be disseminated and implemented in a systematic way to reach all patients eligible for OBS at the time of their surgery. Given the volume of patients undergoing elective MBS with ~40% being eligible for OBS, the results of this study have potential to significantly decrease the rate of HGSC in the general population.

There is no anticipated additional risk to participants in this study. Previous studies looking at the safety of OBS in gynecological and nongynecological surgeries have consistently shown no added perioperative risk. At the advent of OBS, it has always been stated that OBS should only be undertaken if there is no additional perceived risk to the patient. Thus, if the operating surgeon identifies increased risk (e.g. adhesions, unclear anatomy) when completing OBS, then it will not be attempted. Perioperative complications will be graded according to the Clavien-Dindo classification of surgical complications. Any Grade 4 or 5 complications will be immediately reviewed by the study team to determine whether the study needs to be stopped.

Individuals with fallopian tubes (no prior salpingectomy/salpingo-oophorectomy) who are undergoing an elective MBS will be eligible for OBS if they can provide informed consent. All patients (regardless of menopausal status) will be eligible, but premenopausal patients will be counseled regarding their fertility and anyone with a desire for a future pregnancy will be excluded.

Study duration of 6 months will be used to calculate sample size, as feasibility is the primary outcome in this pilot study. All other secondary clinical outcome comparisons will be exploratory. The surgeons at each site perform the following case volumes of MBS monthly: Hamilton: 17, Montreal: 29, Guelph: 9. Expecting that 80% of these patients will be female, 50% will be > 45 years of age (surrogate for child-bearing completion)(26) and operating under a conservative prediction that 50% will agree to OBS, it is anticipated that 11 patients will be recruited per month. Thus, 66 patients will be recruited in 6 months.

The investigators will conduct a multi-center, open label, feasibility clinical trial across three sites in Canada. The participating sites include St. Joseph's Hospital in Hamilton, ON (surgical site lead Dr. D Hong), Montreal Sacred Heart Hospital in Montreal, QC (surgical site lead Dr. R Pescarus) and The Guelph General Hospital in Guelph, ON (surgical site lead Dr. N Pereira-Hong). Ethics will be obtained through all relevant research ethics boards using the trial protocol. All intervention patients will sign a written informed consent form prior to enrolment. The research coordinator at each site will have access to the electronic booking system. They will examine the patient lists a priori to identify those who would be eligible for the study. They will approach patients and offer them the option to participate in a trial of OBS during their MBS. If they are interested, the patient will be provided with electronic consent documents by email and offered a paper version, should they prefer.

The surgical site lead at each site will obtain competence in OBS prior to study onset through educational videos and local gynecology training, with a surgeon who has prior experience in OBS present during the first procedure for each newly trained surgeon. General surgeons will perform OBS following MBS in study participants. Specific instruction will be given to not complete OBS should there be any anticipated extra risk for any reason (adhesions, unclear anatomy). Comparative data will be obtained from retrospective chart review of age-matched historical patients who underwent MBS for analysis of secondary outcomes. The research coordinators will run each potential eligible historical patient by the surgeon running that site to ensure that they would have been eligible for the trial. All identifiable data will be removed and replaced with randomized identification numbers. Given no control patients can be identified and nothing learnt will have direct clinical relevance to the patient, a waiver of consent is deemed ethical (as was granted in previous feasibility and safety trials of OBS during colorectal surgery and LC).

All patient data will be collected at the institution the patient is undergoing surgery at and de-identified by the respective surgical site lead or research coordinator at that site. De-identified, pre-processed data will then be collated at the main study site (Hamilton) for manuscript writing.

The primary outcome of this study will be feasibility of OBS at time of MBS. Feasibility will be defined as the percentage of patients who consented to OBS and went on to successfully have both fallopian tubes removed during MBS. Secondary outcomes include safety outcomes previously studied in OBS in gynecologic surgery and the OBS colorectal trial to ease in result comparison. These will include: a) length of hospital stay, (from admission to discharge); b) 30-day hospital readmission rate, as indicated by any return to hospital with an inpatient stay in the 30 days following discharge from their surgery; c) blood transfusion, as measured by any whole blood or blood parts administered to a patient's bloodstream; d) surgical site infection, which includes any infection that develops at the site of the surgical incision within 30 days that requires treatment. Perioperative complications will be graded according to the Clavien-Dindo classification of surgical complications. Any Grade 4 or 5 complications will be immediately reviewed by the study team to determine whether the study needs to be stopped. Secondary outcomes also include health services consequences: 1) additional OR time required; 2) total OR time; 3) number of additional ports placed; 4) instruments used.

Patients will be contacted 30 days following discharge from their surgery to assess for perioperative complications occurring outside of the operating hospital, which may be missed in chart review.

In examining feasibility of OBS during MBS, the percentage completed and reasons for incomplete OBS will be reported in consented patients. For secondary safety and health services outcomes, MBS patients undergoing OBS will be compared to historical MBS patients using a Chi squared (or Fisher's exact) test versus paired T test, with p-value of 0.05 as threshold for significance. Subgroup analysis of the type of MBS performed will be completed (e.g. sleeve gastrectomy vs. roux-en-y gastric bypass).

Inclusion criteria

• Individuals with fallopian tubes (no prior salpingectomy/salpingo-oophorectomy) who are undergoing an elective MBS and have completed child-bearing

Exclusion criteria

• unable to provide informed consent