Title: Deep infiltrating endometriosis: management by medical treatment versus early surgery: DIAMOND
Funder: Chief Scientist Office, Scotland

Abstract: Endometriosis is a common condition, which can cause severe pain. It affects 1 in 10 women and happens when cells similar to those lining the womb grow outside it, generally on surfaces and organs within the pelvic cavity, causing bleeding, scarring and inflamation. Occasionally, rather than growing on or very near the surface, the endometriosis cells can grow deeper into tissues and organs, such as the bowel, bladder and the vagina causing a painful condition which used to be known as “deep infiltrating endometriosis” and is now called deep endometriosis (DE). _x000D_ DE is treated in one of two ways:_x000D_ • by taking hormones which shrink areas of endometriosis by preventing abnormal cells from growing_x000D_ • by using keyhole (laparoscopic) surgery to remove areas of endometriosis _x000D_ _x000D_ Each treatment has its own benefits and potential drawbacks. Hormones can produce side effects and are not suitable for women who want to get pregnant. They may also not provide sufficient pain relief in some women who may need to have surgery. Keyhole surgery for DE can reduce pain in many women, but the procedure is complex with a risk of damage to surrounding organs like blood vessels, bowel and the bladder. _x000D_ _x000D_ The limited research that has been done in this area suggests that, for women with DE who are not considering immediate pregnancy, hormonal treatment over many months could be as effective as surgery in relieving pain, as long as the bowel is not narrowed by endometriosis. Clinical guidelines state that either hormones or surgery can both be used, but are unable to recommend one over the other in the absence of research directly comparing them. As a result, doctors’ decisions are often based on their personal preferences, resulting in major differences in clinical practice across the NHS. There is an urgent need for a research trial to compare medical (hormonal) management versus surgery for DE, to provide a clear and evidence based answer to this important question. _x000D_ _x000D_ We are proposing a large UK-wide study to compare the benefits and risks of surgery versus medical (hormonal) management as treatments for DE. We will ask patients who have DE which is not causing narrowing of the bowel or ureters (tubes that carry urine and connect the kidneys to the bladder), to opt into this research project. All women who agree to take part will have an equal chance of getting hormonal medical treatment or surgery, and we will monitor their symptoms for 18 months via questionnaires every 6 months. Women in either group can also receive additional pain relief and if the medical treatment is not working, they can opt to receive surgery, but we still want to know about their symptoms. _x000D_ _x000D_ Our team of experts include surgeons, researchers, and patient representatives. Involvement of patients and the public has been achieved by working with the University of Aberdeen's Public Interest Research Group and Endometriosis UK, and carrying out an online survey of women with endometriosis and clinicians. We have a clear plan to share the results of this research with GPs, hospital doctors, professional societies, patient support groups, NHS policy makers and patients. Our findings will be made available to stakeholders through national presentations, publication in medical journals, the media and the website of the national charity, Endometriosis UK.

Lay abstract: Research question_x000D_ What is the clinical and cost-effectiveness of laparoscopic surgery (with or without adjuvant medical treatment) versus medical management alone in women with deep endometriosis (DE)?_x000D_ Background_x000D_ Endometriosis affects up to 10% of women of reproductive age and is chracterised by endometrial tissue growing outwith the uterine cavity. It causes inflammation and adhesions, which can lead to pain and infertility. DE, is a severe form of the condition where endometrial deposits are found more than 5 mm under the peritoneum or any of the following locations: between the rectum and vagina, the Pouch of Douglas, uterosacral ligaments, bowel, appendix, ureter, bladder, uterovesical fold and pelvic side wall. Laparoscopic excision of endometriosis has been shown to improve pain symptoms in DE. It is the only option in women with bowel or ureteric obstruction, but in others, hormonal treatment with the aim of shrinking areas of endometriosis has also been shown to relieve symptoms. Surgery for DE is very invasive and can cause bowel injury, septic peritonitis, rectovaginal fistula formation, stenosis, and bowel or bladder problems. Hormonal treatment is less risky, but can cause side-effects such as menopausal symptoms, and is incompatible with conception. A recent review of observational studies suggests that long-term hormonal treatment could be a viable alternative to surgery, but there are no randomised controlled trials to provide conclusive evidence._x000D_ Aims and objectives_x000D_ To compare the clinical and cost-effectiveness of laparoscopic surgery versus medical treatment for the management of deep endometriosis in terms of condition specific quality of life measured using the pain domain of the Endometriosis Health Profile 30 and incremental cost per QALY gained at 18 months after randomisation. Secondary objectives: To compare surgical removal of DE with medical treatment in terms of pain, need for further medical treatment, gynaecological surgery, discontinuation of randomised treatment, serious adverse events, occupational outcomes and reproductive outcomes, indirect costs due to loss productivity and long term modelled cost effectiveness._x000D_ Methods_x000D_ A multi-centre randomised controlled trial comparing early planned laparoscopic surgery versus medical management alone in women with DE (200 in each arm). Women presenting with pelvic pain associated with confirmed DE who are suitable for either surgical or medical management will be eligible. We will recruit from British Society of Gynaecology Endoscopy (BSGE) accredited endometriosis centres in the UK. A qualitative evaluation is embedded within the RCT to inform the delivery of the trial and explore the patient experience. _x000D_ Timelines for delivery_x000D_ The study duration is 54 months. Milestones: month 1-6, set-up, authorisations; months 7-30: patient recruitment; months 31-48: patient follow up to 18 months post randomisation; months 49-54: data analysis, interpretation of results, report writing and dissemination._x000D_ Anticipated impact and dissemination_x000D_ If hormonal treatment is shown to be superior to surgery, uptake in clinical practice should be rapid as the intervention is relatively nexpensive, does not carry surgical and anaesthetic risks, and can be delivered easily and quickly. Results will be disseminated via Endometriosis UK, professional bodies NHS and university websites, open access journals, clinical practice guidelines and presentations in relevant conferences.

Research activity codes: 6.4 SURGERY
Health categories: REPRODUCTIVE HEALTH AND CHILDBIRTH