Gynaecological cancer surveillance for women with Lynch syndrome: systematic review and cost-effectiveness evaluation.

ABSTRACT

Background: Lynch syndrome is an inherited condition which leads to an increased risk of colorectal, endometrial and ovarian cancer. Risk-reducing surgery is generally recommended to manage the risk of gynaecological cancer once childbearing is completed. The value of gynaecological colonoscopic surveillance as an interim measure or instead of risk-reducing surgery is uncertain. We aimed to determine whether gynaecological surveillance was effective and cost-effective in Lynch syndrome. Methods: We conducted systematic reviews of the effectiveness and cost-effectiveness of gynaecological cancer surveillance in Lynch syndrome, as well as a systematic review of health utility values relating to cancer and gynaecological risk reduction. Study identification included bibliographic database searching and citation chasing (searches updated 3 August 2021). Screening and assessment of eligibility for inclusion were conducted by independent researchers. Outcomes were prespecified and were informed by clinical experts and patient involvement. Data extraction and quality appraisal were conducted and results were synthesised narratively. We also developed a whole-disease economic model for Lynch syndrome using discrete event simulation methodology, including natural history components for colorectal, endometrial and ovarian cancer, and we used this model to conduct a cost-utility analysis of gynaecological risk management strategies, including surveillance, risk-reducing surgery and doing nothing. Results: We found 30 studies in the review of clinical effectiveness, of which 20 were non-comparative (single-arm) studies. There were no high-quality studies providing precise outcome estimates at low risk of bias. There is some evidence that mortality rate is higher for surveillance than for risk-reducing surgery but mortality is also higher for no surveillance than for surveillance. Some asymptomatic cancers were detected through surveillance but some cancers were also missed. There was a wide range of pain experiences, including some individuals feeling no pain and some feeling severe pain. The use of pain relief (e.g. ibuprofen) was common, and some women underwent general anaesthetic for surveillance. Existing economic evaluations clearly found that risk-reducing surgery leads to the best lifetime health (measured using quality-adjusted life-years) and is cost-effective, while surveillance is not cost-effective in comparison. Our economic evaluation found that a strategy of surveillance alone or offering surveillance and risk-reducing surgery was cost-effective, except for path_PMS2 Lynch syndrome. Offering only risk-reducing surgery was less effective than offering surveillance with or without surgery. Limitations: Firm conclusions about clinical effectiveness could not be reached because of the lack of high-quality research. We did not assume that women would immediately take up risk-reducing surgery if offered, and it is possible that risk-reducing surgery would be more effective and cost-effective if it was taken up when offered. Conclusions: There is insufficient evidence to recommend for or against gynaecological cancer surveillance in Lynch syndrome on clinical grounds, but modelling suggests that surveillance could be cost-effective. Further research is needed but it must be rigorously designed and well reported to be of benefit. Study registration This study is registered as PROSPERO CRD42020171098. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref NIHR129713) and is published in full in Health Technology Assessment; Vol. 28, No. 41. See the NIHR Funding and Awards website for further award information.

Lynch syndrome is an inherited condition which puts people at a higher risk of getting bowel cancer, womb cancer and ovarian cancer. Although people with Lynch syndrome are more likely to get these cancers, they are more likely to survive cancer if they get it. People diagnosed with Lynch syndrome get regular testing (surveillance) using a camera to check for bowel cancer or polyps. For womb and ovarian cancer, surveillance may also be an option, but it is less well studied in these cancers. This means that many women are not offered surveillance. Women with Lynch syndrome are recommended to have risk-reducing surgery when their risk starts rising, if they do not want any more children. We wanted to find out whether surveillance for womb and ovarian cancer would work and would be good value for money. Doctors and patients have said that these are important research questions. We searched for published research on this subject and found a lot of studies, but these studies were often small or not well designed, so they could only tell us a limited amount. Studies did not always measure the things that patients want to know. There was some evidence that people having surveillance might live longer than people not having surveillance, but there was also some evidence that risk-reducing surgery is better than surveillance. Surveillance has detected some cancers which had no symptoms, but there are also cancers diagnosed soon after a surveillance visit where nothing was found. People often find surveillance painful, but experiences vary. Our work shows that surveillance and surgery could be good value for money for many women with Lynch syndrome. We need better research to help patients and doctors decide whether surveillance is right for them.