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 Heinimann; CA 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

doi:10.1016/j.ejca.2021.02.022

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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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 language	English
Pages (from-to)	124-133
Journal	EUROPEAN JOURNAL OF CANCER
Volume	148
DOIs	https://doi.org/10.1016/j.ejca.2021.02.022
Publication status	Published - May 2021
Externally published	Yes
Publication type	A1 Journal article-refereed

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10.1016/j.ejca.2021.02.022Licence: CC BY

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Seppälä, T., Dominguez-Valentin, M., Crosbie, EJ., Engel, C., Aretz, S., Macrae, F., Winship, I., Capella, G., Thomas, H., Hovig, E., Nielsen, M., Sijmons, RH., Bertario, L., Bonanni, B., Tibiletti, MG., Cavestro, GM., Mints, M., Gluck, N., Katz, L., ... Moller, P. (2021). Uptake of hysterectomy and bilateral salpingooophorectomy in carriers of pathogenic mismatch repair variants: a Prospective Lynch Syndrome Database report. EUROPEAN JOURNAL OF CANCER, 148, 124-133. https://doi.org/10.1016/j.ejca.2021.02.022

@article{5a0ebe91ff9746d7a6257d4f82b0ab1a,

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

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.",

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

year = "2021",

month = may,

doi = "10.1016/j.ejca.2021.02.022",

language = "English",

volume = "148",

pages = "124--133",

journal = "EUROPEAN JOURNAL OF CANCER",

issn = "0959-8049",

publisher = "Elsevier",

}

Seppälä, T, Dominguez-Valentin, M, Crosbie, EJ, Engel, C, Aretz, S, Macrae, F, Winship, I, Capella, G, Thomas, H, Hovig, E, Nielsen, M, Sijmons, RH, Bertario, L, Bonanni, B, Tibiletti, MG, Cavestro, GM, Mints, M, Gluck, N, Katz, L, Heinimann, K, Vaccaro, CA, Green, K, Lalloo, F, Hill, J, Schmiegel, W, Vangala, D, Perne, C, Strauss, HG, Tecklenburg, J, Holinski-Feder, E, Steinke-Lange, V, Mecklin, JP, Plazzer, JP, Pineda, M, Navarro, M, Vida, JB, Kariv, R, Rosner, G, Pinero, TA, Pavicic, W, Kalfayan, P, Broeke, SWT, Jenkins, MA, Sunde, L, Bernstein, I, Burn, J, Greenblatt, M, Cappel, WHDTN, Valle, AD, Lopez-Koestner, F, Alvarez, K, Buttner, R, Gorgens, H, Morak, M, Holzapfel, S, Huneburg, R, Doeberitz, MV, Loeffler, M, Redler, S, Weitz, J, Pylvanainen, K, Renkonen-Sinisalo, L, Lepistö, AH, Hopper, JL, Win, AK, Lindor, NM, Gallinger, S, Marchand, LL, Newcomb, PA, Figueiredo, JC, Thibodeau, SN, Therkildsen, C, Wadt, KAW, Mourits, MJE, Ketabi, Z, Denton, OG, Rodland, EA, Vasen, H, Neffa, F, Esperon, P, Tjandra, D, Moslein, G, Rokkones, E, Sampson, JR, Evans, DG & Moller, P 2021, 'Uptake of hysterectomy and bilateral salpingooophorectomy in carriers of pathogenic mismatch repair variants: a Prospective Lynch Syndrome Database report', EUROPEAN JOURNAL OF CANCER, vol. 148, pp. 124-133. https://doi.org/10.1016/j.ejca.2021.02.022

TY - JOUR

T1 - Uptake of hysterectomy and bilateral salpingooophorectomy in carriers of pathogenic mismatch repair variants: a Prospective Lynch Syndrome Database report

AU - Seppälä, Toni

AU - Dominguez-Valentin, M

AU - Crosbie, EJ

AU - Engel, C

AU - Aretz, S

AU - Macrae, F

AU - Winship, I

AU - Capella, G

AU - Thomas, H

AU - Hovig, E

AU - Nielsen, M

AU - Sijmons, RH

AU - Bertario, L

AU - Bonanni, B

AU - Tibiletti, MG

AU - Cavestro, GM

AU - Mints, M

AU - Gluck, N

AU - Katz, L

AU - Heinimann, K

AU - Vaccaro, CA

AU - Green, K

AU - Lalloo, F

AU - Hill, J

AU - Schmiegel, W

AU - Vangala, D

AU - Perne, C

AU - Strauss, HG

AU - Tecklenburg, J

AU - Holinski-Feder, E

AU - Steinke-Lange, V

AU - Mecklin, JP

AU - Plazzer, JP

AU - Pineda, M

AU - Navarro, M

AU - Vida, JB

AU - Kariv, R

AU - Rosner, G

AU - Pinero, TA

AU - Pavicic, W

AU - Kalfayan, P

AU - Broeke, SW Ten

AU - Jenkins, MA

AU - Sunde, L

AU - Bernstein, I

AU - Burn, J

AU - Greenblatt, M

AU - Cappel, WHDTN

AU - Valle, A Della

AU - Lopez-Koestner, F

AU - Alvarez, K

AU - Buttner, R

AU - Gorgens, H

AU - Morak, M

AU - Holzapfel, S

AU - Huneburg, R

AU - Doeberitz, MV

AU - Loeffler, M

AU - Redler, S

AU - Weitz, J

AU - Pylvanainen, K

AU - Renkonen-Sinisalo, L

AU - Lepistö, Anna Henriikka

AU - Hopper, JL

AU - Win, AK

AU - Lindor, NM

AU - Gallinger, S

AU - Marchand, LL

AU - Newcomb, PA

AU - Figueiredo, JC

AU - Thibodeau, SN

AU - Therkildsen, C

AU - Wadt, KAW

AU - Mourits, MJE

AU - Ketabi, Z

AU - Denton, OG

AU - Rodland, EA

AU - Vasen, H

AU - Neffa, F

AU - Esperon, P

AU - Tjandra, D

AU - Moslein, G

AU - Rokkones, E

AU - Sampson, JR

AU - Evans, DG

AU - Moller, P

PY - 2021/5

Y1 - 2021/5

N2 - 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.

AB - 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.

U2 - 10.1016/j.ejca.2021.02.022

DO - 10.1016/j.ejca.2021.02.022

M3 - Article

SN - 0959-8049

VL - 148

SP - 124

EP - 133

JO - EUROPEAN JOURNAL OF CANCER

JF - EUROPEAN JOURNAL OF CANCER

ER -

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

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