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

Toni T. Seppälä; Mev Dominguez-Valentin; Emma J. Crosbie; Christoph Engel; Stefan Aretz; Finlay Macrae; Ingrid Winship; Gabriel Capella; Huw Thomas; Eivind Hovig; Maartje Nielsen; Rolf H. Sijmons; Lucio Bertario; Bernardo Bonanni; Maria G. Tibiletti; Giulia M. Cavestro; Miriam Mints; Nathan Gluck; Lior Katz; Karl Heinimann; Carlos A. Vaccaro; Kate Green; Fiona Lalloo; James Hill; Wolff Schmiegel; Deepak Vangala; Claudia Perne; Hans Georg Strauß; Johanna Tecklenburg; Elke Holinski-Feder; Verena Steinke-Lange; Jukka Pekka Mecklin; John Paul Plazzer; Marta Pineda; Matilde Navarro; Joan B. Vida; Revital Kariv; Guy Rosner; Tamara A. Piñero; Walter Pavicic; Pablo Kalfayan; Sanne W. ten Broeke; Mark A. Jenkins; Lone Sunde; Inge Bernstein; John Burn; Marc Greenblatt; Wouter H. de Vos tot Nederveen Cappel; Adriana Della Valle; Francisco Lopez-Koestner; Karin Alvarez; Reinhard Büttner; Heike Görgens; Monika Morak; Stefanie Holzapfel; Robert Hüneburg; Magnus von Knebel Doeberitz; Markus Loeffler; Silke Redler; Jürgen Weitz; Kirsi Pylvänäinen; Laura Renkonen-Sinisalo; Anna Lepistö; John L. Hopper; Aung K. Win; Noralane M. Lindor; Steven Gallinger; Loïc Le Marchand; Polly A. Newcomb; Jane C. Figueiredo; Stephen N. Thibodeau; Christina Therkildsen; Karin A.W. Wadt; Marian J.E. Mourits; Zohreh Ketabi; Oliver G. Denton; Einar A. Rødland; Hans Vasen; Florencia Neffa; Patricia Esperon; Douglas Tjandra; Gabriela Möslein; Erik Rokkones; Julian R. Sampson; D. G. Evans; Pål Møller

doi:10.1016/j.ejca.2021.02.022

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

Toni T. Seppälä^*, Mev Dominguez-Valentin, Emma J. Crosbie, Christoph Engel, Stefan Aretz, Finlay Macrae, Ingrid Winship, Gabriel Capella, Huw Thomas, Eivind Hovig, Maartje Nielsen, Rolf H. Sijmons, Lucio Bertario, Bernardo Bonanni, Maria G. Tibiletti, Giulia M. Cavestro, Miriam Mints, Nathan Gluck, Lior Katz, Karl HeinimannCarlos A. Vaccaro, Kate Green, Fiona Lalloo, James Hill, Wolff Schmiegel, Deepak Vangala, Claudia Perne, Hans Georg Strauß, Johanna Tecklenburg, Elke Holinski-Feder, Verena Steinke-Lange, Jukka Pekka Mecklin, John Paul Plazzer, Marta Pineda, Matilde Navarro, Joan B. Vida, Revital Kariv, Guy Rosner, Tamara A. Piñero, Walter Pavicic, Pablo Kalfayan, Sanne W. ten Broeke, Mark A. Jenkins, Lone Sunde, Inge Bernstein, John Burn, Marc Greenblatt, Wouter H. de Vos tot Nederveen Cappel, Adriana Della Valle, Francisco Lopez-Koestner, Karin Alvarez, Reinhard Büttner, Heike Görgens, Monika Morak, Stefanie Holzapfel, Robert Hüneburg, Magnus von Knebel Doeberitz, Markus Loeffler, Silke Redler, Jürgen Weitz, Kirsi Pylvänäinen, Laura Renkonen-Sinisalo, Anna Lepistö, John L. Hopper, Aung K. Win, Noralane M. Lindor, Steven Gallinger, Loïc Le Marchand, Polly A. Newcomb, Jane C. Figueiredo, Stephen N. Thibodeau, Christina Therkildsen, Karin A.W. Wadt, Marian J.E. Mourits, Zohreh Ketabi, Oliver G. Denton, Einar A. Rødland, Hans Vasen, Florencia Neffa, Patricia Esperon, Douglas Tjandra, Gabriela Möslein, Erik Rokkones, Julian R. Sampson, D. G. Evans, Pål Møller

^*Corresponding author for this work

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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 syndrome to improve outcomes.

Original language	English
Journal	European Journal of Cancer
Volume	148
Pages (from-to)	124-133
Number of pages	10
ISSN	0959-8049
DOIs	https://doi.org/10.1016/j.ejca.2021.02.022
Publication status	Published - May 2021

Keywords

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

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Seppälä et al (2021) Uptake of hysterectomy and bilateral salpingo-oophorectomy in carriers of pathogenic mismatch repair variantsFinal published version, 563 KBLicence: CC BY 4.0

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Seppälä, 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., ... Møller, P. (2021). Uptake of hysterectomy and bilateral salpingo-oophorectomy 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{a7d5b16f7ddb4f9a8dafcb6e98921f78,

title = "Uptake of hysterectomy and bilateral salpingo-oophorectomy 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 syndrome to improve outcomes.",

keywords = "Endometrial cancer, Hysterectomy, Lynch syndrome, MLH1, MSH2, MSH6, Oophorectomy, Ovarian cancer, PMS2, Risk-reducing surgery",

author = "Sepp{\"a}l{\"a}, {Toni T.} and Mev Dominguez-Valentin and Crosbie, {Emma J.} and Christoph Engel and Stefan Aretz and Finlay Macrae and Ingrid Winship and Gabriel Capella and Huw Thomas and Eivind Hovig and Maartje Nielsen and Sijmons, {Rolf H.} and Lucio Bertario and Bernardo Bonanni and Tibiletti, {Maria G.} and Cavestro, {Giulia M.} and Miriam Mints and Nathan Gluck and Lior Katz and Karl Heinimann and Vaccaro, {Carlos A.} and Kate Green and Fiona Lalloo and James Hill and Wolff Schmiegel and Deepak Vangala and Claudia Perne and Strau{\ss}, {Hans Georg} and Johanna Tecklenburg and Elke Holinski-Feder and Verena Steinke-Lange and Mecklin, {Jukka Pekka} and Plazzer, {John Paul} and Marta Pineda and Matilde Navarro and Vida, {Joan B.} and Revital Kariv and Guy Rosner and Pi{\~n}ero, {Tamara A.} and Walter Pavicic and Pablo Kalfayan and {ten Broeke}, {Sanne W.} and Jenkins, {Mark A.} and Lone Sunde and Inge Bernstein and John Burn and Marc Greenblatt and {de Vos tot Nederveen Cappel}, {Wouter H.} and {Della Valle}, Adriana and Francisco Lopez-Koestner and Karin Alvarez and Reinhard B{\"u}ttner and Heike G{\"o}rgens and Monika Morak and Stefanie Holzapfel and Robert H{\"u}neburg and {von Knebel Doeberitz}, Magnus and Markus Loeffler and Silke Redler and J{\"u}rgen Weitz and Kirsi Pylv{\"a}n{\"a}inen and Laura Renkonen-Sinisalo and Anna Lepist{\"o} and Hopper, {John L.} and Win, {Aung K.} and Lindor, {Noralane M.} and Steven Gallinger and {Le Marchand}, Lo{\"i}c and Newcomb, {Polly A.} and Figueiredo, {Jane C.} and Thibodeau, {Stephen N.} and Christina Therkildsen and Wadt, {Karin A.W.} and Mourits, {Marian J.E.} and Zohreh Ketabi and Denton, {Oliver G.} and R{\o}dland, {Einar A.} and Hans Vasen and Florencia Neffa and Patricia Esperon and Douglas Tjandra and Gabriela M{\"o}slein and Erik Rokkones and Sampson, {Julian R.} and Evans, {D. G.} and P{\aa}l M{\o}ller",

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 = "Pergamon Press",

}

Seppälä, TT, 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, Piñero, TA, Pavicic, W, Kalfayan, P, ten Broeke, SW, Jenkins, MA, Sunde, L , Bernstein, I, Burn, J, Greenblatt, M, de Vos tot Nederveen Cappel, WH, Della Valle, A, Lopez-Koestner, F, Alvarez, K, Büttner, R, Görgens, H, Morak, M, Holzapfel, S, Hüneburg, R, von Knebel Doeberitz, M, Loeffler, M, Redler, S, Weitz, J, Pylvänäinen, K, Renkonen-Sinisalo, L, Lepistö, A, Hopper, JL, Win, AK, Lindor, NM, Gallinger, S, Le Marchand, L, Newcomb, PA, Figueiredo, JC, Thibodeau, SN, Therkildsen, C, Wadt, KAW, Mourits, MJE, Ketabi, Z, Denton, OG, Rødland, EA, Vasen, H, Neffa, F, Esperon, P, Tjandra, D, Möslein, G, Rokkones, E, Sampson, JR, Evans, DG & Møller, P 2021, 'Uptake of hysterectomy and bilateral salpingo-oophorectomy 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

Uptake of hysterectomy and bilateral salpingo-oophorectomy in carriers of pathogenic mismatch repair variants: a Prospective Lynch Syndrome Database report. / Seppälä, Toni T.; Dominguez-Valentin, Mev; Crosbie, Emma J. et al.
In: European Journal of Cancer, Vol. 148, 05.2021, p. 124-133.

Research output: Contribution to journal › Journal article › Research › peer-review

TY - JOUR

T1 - Uptake of hysterectomy and bilateral salpingo-oophorectomy in carriers of pathogenic mismatch repair variants

T2 - a Prospective Lynch Syndrome Database report

AU - Seppälä, Toni T.

AU - Dominguez-Valentin, Mev

AU - Crosbie, Emma J.

AU - Engel, Christoph

AU - Aretz, Stefan

AU - Macrae, Finlay

AU - Winship, Ingrid

AU - Capella, Gabriel

AU - Thomas, Huw

AU - Hovig, Eivind

AU - Nielsen, Maartje

AU - Sijmons, Rolf H.

AU - Bertario, Lucio

AU - Bonanni, Bernardo

AU - Tibiletti, Maria G.

AU - Cavestro, Giulia M.

AU - Mints, Miriam

AU - Gluck, Nathan

AU - Katz, Lior

AU - Heinimann, Karl

AU - Vaccaro, Carlos A.

AU - Green, Kate

AU - Lalloo, Fiona

AU - Hill, James

AU - Schmiegel, Wolff

AU - Vangala, Deepak

AU - Perne, Claudia

AU - Strauß, Hans Georg

AU - Tecklenburg, Johanna

AU - Holinski-Feder, Elke

AU - Steinke-Lange, Verena

AU - Mecklin, Jukka Pekka

AU - Plazzer, John Paul

AU - Pineda, Marta

AU - Navarro, Matilde

AU - Vida, Joan B.

AU - Kariv, Revital

AU - Rosner, Guy

AU - Piñero, Tamara A.

AU - Pavicic, Walter

AU - Kalfayan, Pablo

AU - ten Broeke, Sanne W.

AU - Jenkins, Mark A.

AU - Sunde, Lone

AU - Bernstein, Inge

AU - Burn, John

AU - Greenblatt, Marc

AU - de Vos tot Nederveen Cappel, Wouter H.

AU - Della Valle, Adriana

AU - Lopez-Koestner, Francisco

AU - Alvarez, Karin

AU - Büttner, Reinhard

AU - Görgens, Heike

AU - Morak, Monika

AU - Holzapfel, Stefanie

AU - Hüneburg, Robert

AU - von Knebel Doeberitz, Magnus

AU - Loeffler, Markus

AU - Redler, Silke

AU - Weitz, Jürgen

AU - Pylvänäinen, Kirsi

AU - Renkonen-Sinisalo, Laura

AU - Lepistö, Anna

AU - Hopper, John L.

AU - Win, Aung K.

AU - Lindor, Noralane M.

AU - Gallinger, Steven

AU - Le Marchand, Loïc

AU - Newcomb, Polly A.

AU - Figueiredo, Jane C.

AU - Thibodeau, Stephen N.

AU - Therkildsen, Christina

AU - Wadt, Karin A.W.

AU - Mourits, Marian J.E.

AU - Ketabi, Zohreh

AU - Denton, Oliver G.

AU - Rødland, Einar A.

AU - Vasen, Hans

AU - Neffa, Florencia

AU - Esperon, Patricia

AU - Tjandra, Douglas

AU - Möslein, Gabriela

AU - Rokkones, Erik

AU - Sampson, Julian R.

AU - Evans, D. G.

AU - Møller, Pål

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 syndrome to improve outcomes.

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 syndrome to improve outcomes.

KW - Endometrial cancer

KW - Hysterectomy

KW - Lynch syndrome

KW - MLH1

KW - MSH2

KW - MSH6

KW - Oophorectomy

KW - Ovarian cancer

KW - PMS2

KW - Risk-reducing surgery

UR - http://www.scopus.com/inward/record.url?scp=85102799259&partnerID=8YFLogxK

U2 - 10.1016/j.ejca.2021.02.022

DO - 10.1016/j.ejca.2021.02.022

M3 - Journal article

AN - SCOPUS:85102799259

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 salpingo-oophorectomy in carriers of pathogenic mismatch repair variants: a Prospective Lynch Syndrome Database report

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