Risk of Peritoneal Carcinomatosis After Risk-Reducing Salpingo-Oophorectomy: A Systematic Review and Individual Patient Data Meta-Analysis

Author:

Steenbeek Miranda P.1ORCID,van Bommel Majke H.D.1ORCID,Bulten Johan2,Hulsmann Julia A.1ORCID,Bogaerts Joep2ORCID,Garcia Christine3,Cun Han T.4ORCID,Lu Karen H.4ORCID,van Beekhuizen Heleen J.5ORCID,Minig Lucas6ORCID,Gaarenstroom Katja N.7,Nobbenhuis Marielle8,Krajc Mateja9ORCID,Rudaitis Vilius10,Norquist Barbara M.11ORCID,Swisher Elizabeth M.11,Mourits Marian J.E.12ORCID,Massuger Leon F.A.G.1,Hoogerbrugge Nicoline13ORCID,Hermens Rosella P.M.G.14ORCID,IntHout Joanna15,de Hullu Joanne A.1

Affiliation:

1. Radboud University Medical Center, Radboud Institute for Health Sciences, Department of Obstetrics and Gynaecology, Nijmegen, the Netherlands

2. Radboud University Medical Center, Department of Pathology, Nijmegen, the Netherlands

3. Kaiser Permanente Northern California, Division of Gynecologic Oncology San Francisco, San Francisco CA

4. Department of Gynecologic Oncology and Reproductive Medicine, University of Texas MD Anderson Cancer Center, Houston, TX

5. Erasmus MC Cancer Center, University Medical Center Rotterdam, Department of Gynecological Oncology, Rotterdam, the Netherlands

6. Gynecologic Oncology Unit, IMED Hospitales, Valencia, Spain

7. Leiden University Medical Center, Department of Obstetrics and Gynecology, Leiden, the Netherlands

8. The Royal Marsden NHS Foundation Trust, Department of Gynaecology, London, England

9. Institute of Oncology Ljubljana, Department of Clinical Genetics, Ljubljana, Slovenia

10. Vilnius University Faculty of Medicine, Clinic of Obstetrics and Gynecology, Vilnius, Lithuania

11. University of Washington, Division of Gynecologic Oncology, Seattle, WA

12. University Medical Center Groningen, University of Groningen, Department of Gynecologic Oncology, Groningen, the Netherlands

13. Radboud University Medical Center, Department of Human Genetics, Nijmegen, the Netherlands

14. Radboud University Medical Center, Radboud Institute for Health Sciences, Scientific Institute for Quality of Healthcare, Nijmegen, the Netherlands

15. Radboud University Medical Center, Radboud Institute for Health Sciences, Department for Health Evidence, Nijmegen, the Netherlands

Abstract

PURPOSE After risk-reducing salpingo-oophorectomy (RRSO), BRCA1/ 2 pathogenic variant (PV) carriers have a residual risk to develop peritoneal carcinomatosis (PC). The etiology of PC is not yet clarified, but may be related to serous tubal intraepithelial carcinoma (STIC), the postulated origin for high-grade serous cancer. In this systematic review and individual patient data meta-analysis, we investigate the risk of PC in women with and without STIC at RRSO. METHODS Unpublished data from three centers were supplemented by studies identified in a systematic review of EMBASE, MEDLINE, and the Cochrane library describing women with a BRCA-PV with and without STIC at RRSO until September 2020. Primary outcome was the hazard ratio for the risk of PC between BRCA-PV carriers with and without STIC at RRSO, and the corresponding 5- and 10-year risks. Primary analysis was based on a one-stage Cox proportional-hazards regression with a frailty term for study. RESULTS From 17 studies, individual patient data were available for 3,121 women, of whom 115 had a STIC at RRSO. The estimated hazard ratio to develop PC during follow-up in women with STIC was 33.9 (95% CI, 15.6 to 73.9), P < .001) compared with women without STIC. For women with STIC, the five- and ten-year risks to develop PC were 10.5% (95% CI, 6.2 to 17.2) and 27.5% (95% CI, 15.6 to 43.9), respectively, whereas the corresponding risks were 0.3% (95% CI, 0.2 to 0.6) and 0.9% (95% CI, 0.6 to 1.4) for women without STIC at RRSO. CONCLUSION BRCA-PV carriers with STIC at RRSO have a strongly increased risk to develop PC which increases over time, although current data are limited by small numbers of events.

Publisher

American Society of Clinical Oncology (ASCO)

Subject

Cancer Research,Oncology

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