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

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Toni T. Seppälä - , University of Helsinki, Johns Hopkins University, Imperial College London, CALEDONIAN EXCHANGE (Author)
  • Mev Dominguez-Valentin - , University of Oslo, Imperial College London, CALEDONIAN EXCHANGE (Author)
  • Emma J. Crosbie - , Imperial College London, University of Manchester (Author)
  • Christoph Engel - , Leipzig University, Imperial College London (Author)
  • Stefan Aretz - , University of Bonn (Author)
  • Finlay Macrae - , Royal Melbourne Hospital, University of Melbourne, Imperial College London (Author)
  • Ingrid Winship - , Royal Melbourne Hospital, University of Melbourne (Author)
  • Gabriel Capella - , University of Barcelona, Imperial College London, CALEDONIAN EXCHANGE (Author)
  • Huw Thomas - , Imperial College London (Author)
  • Eivind Hovig - , University of Oslo (Author)
  • Maartje Nielsen - , Leiden University (Author)
  • Rolf H. Sijmons - , University of Groningen, Imperial College London, CALEDONIAN EXCHANGE (Author)
  • Lucio Bertario - , IRCCS Istituto Europeo di Oncologia - Milano, IRCCS Fondazione Istituto Nazionale per lo studio e la cura dei tumori - Milano (Author)
  • Bernardo Bonanni - , IRCCS Istituto Europeo di Oncologia - Milano (Author)
  • Maria G. Tibiletti - , University of Insubria (Author)
  • Giulia M. Cavestro - , Vita-Salute San Raffaele University (Author)
  • Miriam Mints - , Karolinska Institutet (Author)
  • Nathan Gluck - , Tel Aviv Sourasky Medical Center, Tel Aviv University (Author)
  • Lior Katz - , Sheba Medical Center at Tel Hashomer (Author)
  • Karl Heinimann - , University of Basel (Author)
  • Carlos A. Vaccaro - , Hospital Italiano de Buenos Aires, Instituto de Medicina Traslacional e Ingenieria Biomedica (IMTIB) (Author)
  • Kate Green - , Manchester University NHS Foundation Trust (Author)
  • Fiona Lalloo - , Manchester University NHS Foundation Trust (Author)
  • James Hill - , Manchester University NHS Foundation Trust (Author)
  • Wolff Schmiegel - , Ruhr University Bochum (Author)
  • Deepak Vangala - , Ruhr University Bochum (Author)
  • Claudia Perne - , University of Bonn (Author)
  • Hans Georg Strauß - , Martin Luther University Halle-Wittenberg (Author)
  • Johanna Tecklenburg - , Hannover Medical School (MHH) (Author)
  • Elke Holinski-Feder - , Ludwig Maximilian University of Munich, MGZ - Medical Genetics Center Munich, Imperial College London, CALEDONIAN EXCHANGE (Author)
  • Verena Steinke-Lange - , Ludwig Maximilian University of Munich, MGZ - Medical Genetics Center Munich (Author)
  • Jukka Pekka Mecklin - , University of Jyväskylä, Imperial College London, CALEDONIAN EXCHANGE (Author)
  • John Paul Plazzer - , Royal Melbourne Hospital, Imperial College London (Author)
  • Marta Pineda - , University of Barcelona (Author)
  • Matilde Navarro - , University of Barcelona (Author)
  • Joan B. Vida - , University of Barcelona (Author)
  • Revital Kariv - , Tel Aviv University (Author)
  • Guy Rosner - , Tel Aviv University (Author)
  • Tamara A. Piñero - , Instituto de Medicina Traslacional e Ingenieria Biomedica (IMTIB) (Author)
  • Walter Pavicic - , Instituto de Medicina Traslacional e Ingenieria Biomedica (IMTIB) (Author)
  • Pablo Kalfayan - , Instituto de Medicina Traslacional e Ingenieria Biomedica (IMTIB) (Author)
  • Sanne W. ten Broeke - , University of Groningen (Author)
  • Mark A. Jenkins - , University of Melbourne (Author)
  • Lone Sunde - , Aalborg University, Aarhus University (Author)
  • Inge Bernstein - , Aalborg University (Author)
  • John Burn - , Newcastle University, Imperial College London, CALEDONIAN EXCHANGE (Author)
  • Marc Greenblatt - , University of Vermont (Author)
  • Wouter H. de Vos tot Nederveen Cappel - , Isala Clinics (Author)
  • Adriana Della Valle - , Central Hospital of the Armed Forces (Author)
  • Jürgen Weitz - , Department of Visceral, Thoracic and Vascular Surgery, National Center for Tumor Diseases Dresden, University Hospital Carl Gustav Carus Dresden (Author)

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.

Details

Original languageEnglish
Pages (from-to)124-133
Number of pages10
JournalEuropean journal of cancer
Volume148
Publication statusPublished - May 2021
Peer-reviewedYes

External IDs

PubMed 33743481

Keywords

Sustainable Development Goals

ASJC Scopus subject areas

Keywords

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