Lim N.1, Macrae F.1,2, Hickey M.1,4, Kelly C.4
1University of Melbourne, Melbourne, Australia, 2Department of Colorectal Medicine and Genetics, Royal Melbourne Hospital, Melbourne, Australia, 3Department of Obstetrics and Gynaecology, Royal Women's Hospital, Melbourne, Australia, 4Department of Gastroenterology, Royal Melbourne Hospital, Melbourne, Australia
Background/Aims: Lynch Syndrome is a hereditary cancer syndrome which increases the risk of multiple cancers, including endometrial cancer and ovarian cancer. Mutations in mismatch repair (MMR) genes or EPCAM predispose to Lynch Syndrome. Screening or risk-reducing surgery is practiced at different centres to prevent gynaecological cancers. However, practice varies because evidence to guide practice is limited.
Methods: Search strategies were conducted on Medline, Embase, and PubMed. Studies reporting the incidence of cancer in screened, asymptomatic women, or histopathological results from prophylactic hysterectomy and/or salpingo-oophorectomy in women predisposed to Lynch Syndrome were included.
Results: 18 studies which screened for endometrial cancer using transvaginal ultrasound and/or hysteroscopy/endometrial biopsy revealed an incidence of 3.8% at the time of screening. Screening detected 68.1% of endometrial cancers in MMR carriers with the balance detected during intervals or through symptoms. The sensitivity of endometrial screening was 71.0%, and Number Needed to Screen (NNS) was between 4 to 27 (median 6). 12 studies which screened for ovarian cancer using transvaginal ultrasound and/or CA-125 revealed an incidence of 1.3% at time of screening. Screening diagnosed 37.5% of ovarian cancers in MMR carriers. The sensitivity of ovarian screening was 40.9%, and NNS was between 9 to 191 (median 23). 9 studies reporting prophylactic specimen results after risk-reducing surgery diagnosed endometrial cancer in 6.9%, and ovarian cancer in 0.8%.
Conclusion: There is limited evidence to support screening for gynaecological cancers in LS. Further prospective, randomised trials comparing targeted screening methods for gynaecological cancers would be useful. At present, RRS remains the mainstay in preventing the development of gynaecological cancer.
Keywords: Lynch Syndrome, Screening, Endometrial biopsy, Transvaginal ultrasound, Risk-reducing surgery