The prevalence of Lynch syndrome in women with endometrial cancer: a systematic review protocol

Background: Lynch syndrome is the most common inherited cancer syndrome, which predisposes individuals to a number of different cancers, principally colorectal and endometrial cancer. The early diagnosis of Lynch syndrome enables colorectal surveillance, which has been shown to save lives through the detection and removal of premalignant polyps and earlier detection of invasive disease. Endometrial cancer, which is often the sentinel cancer in women, provides an opportunity to diagnose Lynch syndrome and thus enable colorectal surveillance as well as the cascade testing for Lynch syndrome in other family members. These potential benefits have led to a call for the universal screening of women with endometrial cancer for Lynch syndrome, a practice that is now commonplace in colorectal cancer. Healthcare providers and clinicians are however restricted by insufficient knowledge about the prevalence of Lynch syndrome in women with endometrial cancer, with estimates varying as widely as 1-10%. The aim of this study is to perform a systematic review with a meta-analysis of the current literature base in order to estimate the prevalence of Lynch syndrome among women with endometrial cancer to inform this discussion. Methods: Medline, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), Cochrane Methodology Register, NHS Health and Technology Assessment Database and the Web of Science will be systematically searched for relevant studies via the Ovid platform. Two authors will review the titles and abstracts independently, with discrepancy settled by a third author. Data extraction will be completed to record demographic, pathological and clinical data, as well as the diagnostic methods used for estimating the prevalence of Lynch syndrome in women with endometrial cancer. Bias will be assessed and recorded using the Newcastle-Ottawa Scale and that of the International Cochrane Collaboration. Dependent on the heterogeneity of the data, we aim to produce a cumulative incidence in addition to subgroup analyses as to investigate secondary outcomes. Discussion: The aim of this systematic review is to provide a robust estimate of the prevalence of Lynch syndrome in women with endometrial cancer. This will enable resource allocation and decision-making regarding the appropriateness of screening all women, or certain women, with endometrial cancer for Lynch syndrome. Such a policy could enable the earlier diagnosis of Lynch syndrome in women and, through the application of colorectal cancer surveillance, improve their survival outcomes.