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

Toni Seppälä, M Dominguez-Valentin, EJ Crosbie, C Engel, S Aretz, F Macrae, I Winship, G Capella, H Thomas, E Hovig, M Nielsen, RH Sijmons, L Bertario, B Bonanni, MG Tibiletti, GM Cavestro, M Mints, N Gluck, L Katz, K HeinimannCA Vaccaro, K Green, F Lalloo, J Hill, W Schmiegel, D Vangala, C Perne, HG Strauss, J Tecklenburg, E Holinski-Feder, V Steinke-Lange, JP Mecklin, JP Plazzer, M Pineda, M Navarro, JB Vida, R Kariv, G Rosner, TA Pinero, W Pavicic, P Kalfayan, SW Ten Broeke, MA Jenkins, L Sunde, I Bernstein, J Burn, M Greenblatt, WHDTN Cappel, A Della Valle, F Lopez-Koestner, K Alvarez, R Buttner, H Gorgens, M Morak, S Holzapfel, R Huneburg, MV Doeberitz, M Loeffler, S Redler, J Weitz, K Pylvanainen, L Renkonen-Sinisalo, Anna Henriikka Lepistö, JL Hopper, AK Win, NM Lindor, S Gallinger, LL Marchand, PA Newcomb, JC Figueiredo, SN Thibodeau, C Therkildsen, KAW Wadt, MJE Mourits, Z Ketabi, OG Denton, EA Rodland, H Vasen, F Neffa, P Esperon, D Tjandra, G Moslein, E Rokkones, JR Sampson, DG Evans, P Moller

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12 Citations (Scopus)

Abstract

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.
Original languageEnglish
Pages (from-to)124-133
JournalEUROPEAN JOURNAL OF CANCER
Volume148
DOIs
Publication statusPublished - May 2021
Externally publishedYes
Publication typeA1 Journal article-refereed

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