Outcomes of endometrial cancer prevention strategies in patients with Lynch syndrome: a nationwide cohort study in the NetherlandsResearch in context
Summary: Background: Female Lynch syndrome carriers have an increased risk of developing endometrial cancer. Regardless, research on endometrial carcinoma tumorigenesis is scarce and no uniform, evidence-based gynaecological management guidelines exist. We therefore described gynaecological surveil...
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2025-01-01
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| author | Ellis L. Eikenboom Lotte van Leeuwen Floris Groenendijk Jorien M. Woolderink Anne M. Van Altena Monique E. Van Leerdam Manon C.W. Spaander Helena C. van Doorn Anja Wagner M.C. Breijer A.S. Tjalsma F. Vork H.P.M. Smedts J. van der Velden M.M.A. Brood-van Zanten J.E. van de Riet A.L.M. Oei H. Kessel P.M.L.H. Vencken M.P.L.M. Snijders R.H.M. Hermans A. Bouman H.W. Ünsalan A.M.G. van de Swaluw G.M. Plaisier H.C. van Doorn K. van den Berg W. Hofhuis Y.A.J.M. Dabekausen P.R. Kolk H.T.C. Nagel A.M.L.D. van Haaften-de Jong A.C. van Hof M. van den Hende J. Kaijser H.H. de Haan R.A. Smit M.W.G. Moonen-Delarue J.J. Beltman J.E. Martens R. Kruitwagen J.M. van der Ploeg J.M. Woolderink S.F.P.J. Coppus M.J. Duk M.J.A. Apperloo C.M. Koopmans C.C.M. Buis H. van Meurs E.C. Dul B.B.J. Hermsen A.M. van Altena A. Baalbergen A.A. van Ginkel-Terng M. Baas P. van Greunen C.M.W.H. Smeets H. Knipscheer J.E. Martens C. Schmeink M.D. van der Laan E.J.M. van Es J.E.W. van Dijk F.M.F. Rosier-van Dunné H. Nijman C.G. Gerestein D. Boskamp E.C.A.H. Scheers M. Verbruggen L.R. Bartelink C.B.M. Kruijdenberg J.M. Briët B. Visschers M. Engelen |
| author_facet | Ellis L. Eikenboom Lotte van Leeuwen Floris Groenendijk Jorien M. Woolderink Anne M. Van Altena Monique E. Van Leerdam Manon C.W. Spaander Helena C. van Doorn Anja Wagner M.C. Breijer A.S. Tjalsma F. Vork H.P.M. Smedts J. van der Velden M.M.A. Brood-van Zanten J.E. van de Riet A.L.M. Oei H. Kessel P.M.L.H. Vencken M.P.L.M. Snijders R.H.M. Hermans A. Bouman H.W. Ünsalan A.M.G. van de Swaluw G.M. Plaisier H.C. van Doorn K. van den Berg W. Hofhuis Y.A.J.M. Dabekausen P.R. Kolk H.T.C. Nagel A.M.L.D. van Haaften-de Jong A.C. van Hof M. van den Hende J. Kaijser H.H. de Haan R.A. Smit M.W.G. Moonen-Delarue J.J. Beltman J.E. Martens R. Kruitwagen J.M. van der Ploeg J.M. Woolderink S.F.P.J. Coppus M.J. Duk M.J.A. Apperloo C.M. Koopmans C.C.M. Buis H. van Meurs E.C. Dul B.B.J. Hermsen A.M. van Altena A. Baalbergen A.A. van Ginkel-Terng M. Baas P. van Greunen C.M.W.H. Smeets H. Knipscheer J.E. Martens C. Schmeink M.D. van der Laan E.J.M. van Es J.E.W. van Dijk F.M.F. Rosier-van Dunné H. Nijman C.G. Gerestein D. Boskamp E.C.A.H. Scheers M. Verbruggen L.R. Bartelink C.B.M. Kruijdenberg J.M. Briët B. Visschers M. Engelen |
| author_sort | Ellis L. Eikenboom |
| collection | DOAJ |
| description | Summary: Background: Female Lynch syndrome carriers have an increased risk of developing endometrial cancer. Regardless, research on endometrial carcinoma tumorigenesis is scarce and no uniform, evidence-based gynaecological management guidelines exist. We therefore described gynaecological surveillance and surgery outcomes in a nation-wide Lynch syndrome cohort. Methods: For this retrospective cohort study, female Lynch syndrome carriers, prospectively registered in the Dutch Lynch syndrome database (StOET), were included up to February 28th 2022. Carriers were linked to the Dutch national pathology (PALGA) database. The number of carriers with/without gynaecological surveillance, number of index carriers with endometrial carcinoma before Lynch syndrome diagnosis were assessed, as well as uptake of risk-reducing surgery and characteristics of endometrial carcinomas including the requisite for adjuvant therapy according to current guidelines. Overall survival after endometrial carcinoma diagnosis was analyzed using Kaplan Meier time to event analyses, cumulative incidence was calculated after adjusting for competing risks (death and prophylactic hysterectomy). Findings: In total, 1046 registered female Lynch syndrome carriers were eligible for surveillance, of whom 313 (30.0%) did not have surveillance and 21.4% (n = 224 of 1046) opted for prophylactic hysterectomy. In carriers with surveillance, more cases of endometrial carcinoma and hyperplasia were found than in those without (37 endometrial carcinomas (7.3%) and 28 hyperplasias (5.5%) in 506 carriers with surveillance versus 14 (2.6%) and 4 (0.7%) in 540 carriers without surveillance, respectively); carriers with surveillance were generally younger than those without (median 56 years [IQR 48–65] versus median 65 years [IQR 49–75] at database assembly, respectively; p < 0.0001). Endometrial carcinomas were predominantly of endometrioid type and FIGO stage IA, regardless of surveillance. Adjuvant external beam radiotherapy was required in one patient in both groups. Overall survival after endometrial carcinoma diagnosis did not differ between carriers with or without surveillance or carriers with endometrial carcinoma before LS diagnosis (p = 0.51). For all endometrial carcinomas together, including index carriers, cumulative incidence was 22.7% at age 70. Interpretation: In a nation-wide cohort of Lynch syndrome carriers, nearly one-third of eligible carriers did not undergo gynaecological surveillance. Endometrial carcinomas diagnosed during surveillance were slightly more often stage FIGO IA, but this did not seem to substantially decrease the requisite for adjuvant therapy or affect overall survival, questioning effectiveness of current gynaecological management. Prospective research should further assess this, as well as patient preferences. Funding: None. |
| format | Article |
| id | doaj-art-7e88a2832b554f9f8c3c08724e51e208 |
| institution | Kabale University |
| issn | 2589-5370 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EClinicalMedicine |
| spelling | doaj-art-7e88a2832b554f9f8c3c08724e51e2082025-01-22T05:43:38ZengElsevierEClinicalMedicine2589-53702025-01-0179103006Outcomes of endometrial cancer prevention strategies in patients with Lynch syndrome: a nationwide cohort study in the NetherlandsResearch in contextEllis L. Eikenboom0Lotte van Leeuwen1Floris Groenendijk2Jorien M. Woolderink3Anne M. Van Altena4Monique E. Van Leerdam5Manon C.W. Spaander6Helena C. van Doorn7Anja Wagner8M.C. BreijerA.S. TjalsmaF. VorkH.P.M. SmedtsJ. van der VeldenM.M.A. Brood-van ZantenJ.E. van de RietA.L.M. OeiH. KesselP.M.L.H. VenckenM.P.L.M. SnijdersR.H.M. HermansA. BoumanH.W. ÜnsalanA.M.G. van de SwaluwG.M. PlaisierH.C. van DoornK. van den BergW. HofhuisY.A.J.M. DabekausenP.R. KolkH.T.C. NagelA.M.L.D. van Haaften-de JongA.C. van HofM. van den HendeJ. KaijserH.H. de HaanR.A. SmitM.W.G. Moonen-DelarueJ.J. BeltmanJ.E. MartensR. KruitwagenJ.M. van der PloegJ.M. WoolderinkS.F.P.J. CoppusM.J. DukM.J.A. ApperlooC.M. KoopmansC.C.M. BuisH. van MeursE.C. DulB.B.J. HermsenA.M. van AltenaA. BaalbergenA.A. van Ginkel-TerngM. BaasP. van GreunenC.M.W.H. SmeetsH. KnipscheerJ.E. MartensC. SchmeinkM.D. van der LaanE.J.M. van EsJ.E.W. van DijkF.M.F. Rosier-van DunnéH. NijmanC.G. GeresteinD. BoskampE.C.A.H. ScheersM. VerbruggenL.R. BartelinkC.B.M. KruijdenbergJ.M. BriëtB. VisschersM. EngelenDepartment of Clinical Genetics, Erasmus MC Cancer Institute, Rotterdam, the Netherlands; Department of Gastroenterology & Hepatology, Erasmus MC Cancer Institute, Rotterdam, the NetherlandsDepartment of Clinical Genetics, Erasmus MC Cancer Institute, Rotterdam, the NetherlandsDepartment of Pathology, Erasmus MC Cancer Institute, Rotterdam, the NetherlandsDepartment of Obstetrics and Gynecology, Martini Hospital Groningen, Groningen, the NetherlandsDivision of Gynecologic Oncology, Department of Obstetrics and Gynecology, Radboud University Medical Centre, Nijmegen, the NetherlandsDepartment of Gastroenterology and Hepatology, Leiden University Medical Center, the Netherlands; Department of Gastrointestinal Oncology, Netherlands Cancer Institute Amsterdam, the NetherlandsDepartment of Gastroenterology & Hepatology, Erasmus MC Cancer Institute, Rotterdam, the NetherlandsDepartment of Gynecologic Oncology, Erasmus MC Cancer Institute, Rotterdam, the NetherlandsDepartment of Clinical Genetics, Erasmus MC Cancer Institute, Rotterdam, the Netherlands; Corresponding author.Summary: Background: Female Lynch syndrome carriers have an increased risk of developing endometrial cancer. Regardless, research on endometrial carcinoma tumorigenesis is scarce and no uniform, evidence-based gynaecological management guidelines exist. We therefore described gynaecological surveillance and surgery outcomes in a nation-wide Lynch syndrome cohort. Methods: For this retrospective cohort study, female Lynch syndrome carriers, prospectively registered in the Dutch Lynch syndrome database (StOET), were included up to February 28th 2022. Carriers were linked to the Dutch national pathology (PALGA) database. The number of carriers with/without gynaecological surveillance, number of index carriers with endometrial carcinoma before Lynch syndrome diagnosis were assessed, as well as uptake of risk-reducing surgery and characteristics of endometrial carcinomas including the requisite for adjuvant therapy according to current guidelines. Overall survival after endometrial carcinoma diagnosis was analyzed using Kaplan Meier time to event analyses, cumulative incidence was calculated after adjusting for competing risks (death and prophylactic hysterectomy). Findings: In total, 1046 registered female Lynch syndrome carriers were eligible for surveillance, of whom 313 (30.0%) did not have surveillance and 21.4% (n = 224 of 1046) opted for prophylactic hysterectomy. In carriers with surveillance, more cases of endometrial carcinoma and hyperplasia were found than in those without (37 endometrial carcinomas (7.3%) and 28 hyperplasias (5.5%) in 506 carriers with surveillance versus 14 (2.6%) and 4 (0.7%) in 540 carriers without surveillance, respectively); carriers with surveillance were generally younger than those without (median 56 years [IQR 48–65] versus median 65 years [IQR 49–75] at database assembly, respectively; p < 0.0001). Endometrial carcinomas were predominantly of endometrioid type and FIGO stage IA, regardless of surveillance. Adjuvant external beam radiotherapy was required in one patient in both groups. Overall survival after endometrial carcinoma diagnosis did not differ between carriers with or without surveillance or carriers with endometrial carcinoma before LS diagnosis (p = 0.51). For all endometrial carcinomas together, including index carriers, cumulative incidence was 22.7% at age 70. Interpretation: In a nation-wide cohort of Lynch syndrome carriers, nearly one-third of eligible carriers did not undergo gynaecological surveillance. Endometrial carcinomas diagnosed during surveillance were slightly more often stage FIGO IA, but this did not seem to substantially decrease the requisite for adjuvant therapy or affect overall survival, questioning effectiveness of current gynaecological management. Prospective research should further assess this, as well as patient preferences. Funding: None.http://www.sciencedirect.com/science/article/pii/S2589537024005856Lynch syndromeGynaecological surveillanceEndometrial carcinoma |
| spellingShingle | Ellis L. Eikenboom Lotte van Leeuwen Floris Groenendijk Jorien M. Woolderink Anne M. Van Altena Monique E. Van Leerdam Manon C.W. Spaander Helena C. van Doorn Anja Wagner M.C. Breijer A.S. Tjalsma F. Vork H.P.M. Smedts J. van der Velden M.M.A. Brood-van Zanten J.E. van de Riet A.L.M. Oei H. Kessel P.M.L.H. Vencken M.P.L.M. Snijders R.H.M. Hermans A. Bouman H.W. Ünsalan A.M.G. van de Swaluw G.M. Plaisier H.C. van Doorn K. van den Berg W. Hofhuis Y.A.J.M. Dabekausen P.R. Kolk H.T.C. Nagel A.M.L.D. van Haaften-de Jong A.C. van Hof M. van den Hende J. Kaijser H.H. de Haan R.A. Smit M.W.G. Moonen-Delarue J.J. Beltman J.E. Martens R. Kruitwagen J.M. van der Ploeg J.M. Woolderink S.F.P.J. Coppus M.J. Duk M.J.A. Apperloo C.M. Koopmans C.C.M. Buis H. van Meurs E.C. Dul B.B.J. Hermsen A.M. van Altena A. Baalbergen A.A. van Ginkel-Terng M. Baas P. van Greunen C.M.W.H. Smeets H. Knipscheer J.E. Martens C. Schmeink M.D. van der Laan E.J.M. van Es J.E.W. van Dijk F.M.F. Rosier-van Dunné H. Nijman C.G. Gerestein D. Boskamp E.C.A.H. Scheers M. Verbruggen L.R. Bartelink C.B.M. Kruijdenberg J.M. Briët B. Visschers M. Engelen Outcomes of endometrial cancer prevention strategies in patients with Lynch syndrome: a nationwide cohort study in the NetherlandsResearch in context EClinicalMedicine Lynch syndrome Gynaecological surveillance Endometrial carcinoma |
| title | Outcomes of endometrial cancer prevention strategies in patients with Lynch syndrome: a nationwide cohort study in the NetherlandsResearch in context |
| title_full | Outcomes of endometrial cancer prevention strategies in patients with Lynch syndrome: a nationwide cohort study in the NetherlandsResearch in context |
| title_fullStr | Outcomes of endometrial cancer prevention strategies in patients with Lynch syndrome: a nationwide cohort study in the NetherlandsResearch in context |
| title_full_unstemmed | Outcomes of endometrial cancer prevention strategies in patients with Lynch syndrome: a nationwide cohort study in the NetherlandsResearch in context |
| title_short | Outcomes of endometrial cancer prevention strategies in patients with Lynch syndrome: a nationwide cohort study in the NetherlandsResearch in context |
| title_sort | outcomes of endometrial cancer prevention strategies in patients with lynch syndrome a nationwide cohort study in the netherlandsresearch in context |
| topic | Lynch syndrome Gynaecological surveillance Endometrial carcinoma |
| url | http://www.sciencedirect.com/science/article/pii/S2589537024005856 |
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