Uptake of hysterectomy and bilateral salpingooophorectomy in carriers of pathogenic mismatch repair variants: a Prospective Lynch Syndrome Database report

Seppala, T.T.; Dominguez-Valentin, M.; Crosbie, E.J.; Engel, C.; Aretz, S.; Macrae, F.; ... ; Moller, P. (2021)

Article / Letter to editor

Purpose: This study aimed to report the uptake of hysterectomy and/or bilateral salpingo-oophorectomy (BSO) to prevent gynaecological cancers (risk-reducing surgery [RRS]) in carriers of pathogenic MMR (path_MMR) variants.Methods: The Prospective Lynch Syndrome Database (PLSD) was used to investigate RRS by a cross-sectional study in 2292 female path_MMR carriers aged 30-69 years.Results: Overall, 144, 79, and 517 carriers underwent risk-reducing hysterectomy, BSO, or both combined, respectively. Two-thirds of procedures before 50 years of age were combined hysterectomy and BSO, and 81% of all procedures included BSO. Risk-reducing hysterectomy was performed before age 50 years in 28%, 25%, 15%, and 9%, and BSO in 26%, 25%, 14% and 13% of path_MLH1, path_MSH2, path_MSH6, and path_PMS2 carriers, respectively. Before 50 years of age, 107 of 188 (57%) BSO and 126 of 204 (62%) hysterectomies were performed in women without any prior cancer, and only 5% (20/392) were performed simultaneously with colorectal cancer (CRC) surgery.Conclusion: Uptake of RRS before 50 years of age was low, and RRS was rarely undertaken in association with surgical treatment of CRC. Uptake of RRS aligned poorly with gene-and age-associated risk estimates for endometrial or ovarian cancer that were published recently from PLSD and did not correspond well with current clinical guidelines. The reasons should be clarified. Decision-making on opting for or against RRS and its timing should be better aligned with predicted risk and mortality for endometrial and ovarian cancer in Lynch syn-drome to improve outcomes. (C) 2021 The Author(s). Published by Elsevier Ltd.

• Lynch syndrome
• Endometrial cancer
• Ovarian cancer
• Risk-reducing surgery
• Hysterectomy
• Oophorectomy
• MLH1
• MSH2
• MSH6
• PMS2

• All authors: Seppala, T.T.; Dominguez-Valentin, M.; Crosbie, E.J.; Engel, C.; Aretz, S.; Macrae, F.; Winship, I.; Capella, G.; Thomas, H.; Hovig, E.; Nielsen, M.; Sijmons, R.H.; Bertario, L.; Bonanni, B.; Tibiletti, M.G.; Cavestro, G.M.; Mints, M.; Gluck, N.; Katz, L.; Heinimann, K.; Vaccaro, C.A.; Green, K.; Lalloo, F.; Hill, J.; Schmiegel, W.; Vangala, D.; Perne, C.; Strauss, H.G.; Tecklenburg, J.; Holinski-Feder, E.; Steinke-Lange, V.; Mecklin, J.P.; Plazzer, J.P.; Pineda, M.; Navarro, M.; Vida, J.B.; Kariv, R.; Rosner, G.; Pinero, T.A.; Pavicic, W.; Kalfayan, P.; Broeke, S.W. ten; Jenkins, M.A.; Sunde, L.; Bernstein, I.; Burn, J.; Greenblatt, M.; Cappel, W.H.D.T.N.; Valle, A. della; Lopez-Koestner, F.; Alvarez, K.; Buttner, R.; Gorgens, H.; Morak, M.; Holzapfel, S.; Huneburg, R.; Doeberitz, M.V.; Loeffler, M.; Redler, S.; Weitz, J.; Pylvanainen, K.; Renkonen-Sinisalo, L.; Lepisto, A.; Hopper, J.L.; Win, A.K.; Lindor, N.M.; Gallinger, S.; Marchand, L.L.; Newcomb, P.A.; Figueiredo, J.C.; Thibodeau, S.N.; Therkildsen, C.; Wadt, K.A.W.; Mourits, M.J.E.; Ketabi, Z.; Denton, O.G.; Rodland, E.A.; Vasen, H.; Neffa, F.; Esperon, P.; Tjandra, D.; Moslein, G.; Rokkones, E.; Sampson, J.R.; Evans, D.G.; Moller, P.
• Date: 2021-05-01
• Journal: European Journal of Cancer
• Volume: 148
• Pages: 124 - 133
• DOI: doi:10.1016/j.ejca.2021.02.022
• Link: http://www.ejcancer.com/article/S0959804921001052/pdf