Title: Follow up for PROSPECT Study
Funder: Chief Scientist Office, Scotland

Abstract: Around 1 in 10 women will need prolapse surgery at some point in their lives. Prolapse occurs when the pelvic organs (such as the bladder, bowel or womb) come down into, or out of, the vagina. This is caused either by weakness of the connective tissues which normally support these organs or by weak pelvic floor muscles. It is most common in women who have had children, although there has been surprisingly little research into its causes and treatment._x000D_ There are many different operations for prolapse, depending on the type of prolapse, whether the woman is having their first or a secondary repair and the preference of the gynaecological surgeon. To date, there is a recurrence rate after surgery: three in ten women who have an operation may develop recurrent prolapse. To help improve failure rates, and because it had worked well for hernia repairs, surgeons started to use synthetic mesh (as an inlay or kit) and graft materials to reinforce the surgery._x000D_ In 2009, the HTA funded the PROSPECT study to look at improvement of prolapse symptoms following surgery using these new mesh and graft techniques compared to standard surgery with no mesh._x000D_ Between January 2010 and August 2013, 3,089 women joined the study from 35 hospitals across the UK. Women having their first repair were randomly allocated to receive either standard surgery (no mesh), prolapse surgery with a synthetic mesh inlay or prolapse surgery with graft material. Women having their second repair were randomly allocated to receive either standard surgery (no mesh), prolapse surgery with a synthetic mesh inlay or prolapse surgery with a synthetic mesh kit. Women could also choose which operation they wanted._x000D_ For 6 years after the operation women completed questionnaires providing information on prolapse symptoms and the impact of prolapse surgery on their urinary, bowel and sexual function. They also told us if they needed further prolapse surgery or experienced any problems with the mesh or graft material._x000D_ We would now like to ask the PROSPECT women to continue providing information up to 14 years after their prolapse surgery. This is because (1) on average, prolapse operations fail after about 12 years and therefore it is still too early to say whether the mesh or graft materials have improved failure rates and (2) there has been much public debate on the use of mesh and graft material and it is important to look at the long-term complications of their use._x000D_ We therefore plan to continue sending the PROSPECT women questionnaires every two years (to 14 years) to collect information on prolapse symptoms and other related outcomes. Information on further prolapse treatments, or treatments for complications of the mesh and graft materials, will be collected from medical records and routine data sources. _x000D_ When complete, the long-term results of the PROSPECT study will provide information on what happens to women after prolapse surgery, with and without synthetic mesh or graft material. This information will help surgeons and women to better understand the benefits and risks of prolapse surgery and help women in the future make better-informed decisions about the benefits and risks of prolapse surgery.

Lay abstract: Research question: What is the long-term effectiveness, including safety, and cost-effectiveness, of surgical treatment for anterior and/or posterior vaginal wall pelvic organ prolapse?_x000D_ Background: Pelvic organ prolapse (POP) is the descent of vaginal and associated pelvic organs from their normal anatomical position. Women have a lifetime risk of 7% of undergoing prolapse surgery. PROSPECT recruited 3089 women; it is therefore the most comprehensive study of prolapse surgery ever performed. The women received either polypropylene mesh, biological xenograft or a native tissue repair. At 6 years after surgery recurrent symptoms were found in 35-40% of women. However, there was no significant difference between treatment groups. _x000D_ Although PROSPECT has not, to date, shown any benefit from the use of mesh or biological grafts, there may be longer term benefit which will only be revealed by longer term follow-up of the PROSPECT women. It is possible that longer term benefit could outweigh shorter term complications. _x000D_ Complications specifically associated with the use of mesh, has led to its suspension in some countries. Evidence collected during the Cumberlege inquiry highlighted serious side effects from the use of mesh and shortcomings in medical practice. We therefore have duty of care to provide long-term follow-up for women randomised to mesh._x000D_ Aim: To determine the long-term effectiveness (including safety) and cost-effectiveness of the use of polypropylene mesh (either as an inlay or using an introducer device) and biological xenograft compared with native tissue repair for women who underwent surgery between January 2010 and August 2013._x000D_ Methods: Follow-up of PROSPECT participants to 14 years using biennial questionnaires. The primary outcome is participant-reported frequency of prolapse symptoms on the Pelvic Organ Prolapse Symptom Scale. Secondary outcomes include impact of surgery on urinary, bowel and sexual function; pain; late onset adverse effects including need for mesh removal; and need for further treatment. Need for further surgery (including surgery for mesh removal) will use a combination of participant reports and routine data. The economic outcome is incremental cost per quality adjusted life years gained. Analysis will be based on the intention-to-treat principle_x000D_ Timeline: Start 1st May 2021. Months 1-4: Initiation and complete 8-year follow-up; Months 1-30: complete 10-year follow-up; Months 8-54: complete 12-year follow-up; Months 31-34: 10-year analysis and publication; Months 32-78: complete 14-years follow-up; Months 73-78: collect routine data; Months 79-84: final analysis and write up._x000D_ Impact and dissemination: The PROSPECT long-term results are expected to have a significant impact on clinical and NHS practice. It is the only comprehensive study of prolapse which will be able answer the long-term effectiveness of treatments for POP. The Cumberlege report (First Do No Harm) called for such robust and independent research. The results of the trial will be included in updates of NICE guidelines, which directly influence practice in the UK and worldwide.

Research activity codes: 6.3 MEDICAL DEVICES;6.4 SURGERY
Health categories: RENAL AND UROGENITAL