
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 METHODS Unpublished data from three centers were supplemented by studies identified in a systematic review of EMBASE, MEDLINE, and the Cochrane library describing women with a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.
CLINICAL-OUTCOMES, Heterozygote, SURGERY, Ovariectomy, Radboudumc 17: Women's cancers RIHS: Radboud Institute for Health Sciences, Salpingo-oophorectomy, Radboud University Medical Center, NEOPLASIA, MUTATION CARRIERS, OVARIAN-CANCER, Gynaecology - Radboud University Medical Center, SDG 3 - Good Health and Well-being, BREAST-CANCER, Fallopian Tube Neoplasms, Humans, Haematology - Radboud University Medical Center, Peritoneal Neoplasms, TUBAL INTRAEPITHELIAL CARCINOMA, Ovarian Neoplasms, SEROUS CARCINOMA, Pathology - Radboud University Medical Center, WOMEN, BRCA1, Cystadenocarcinoma, Serous, IQ Healthcare - Radboud University Medical Center, Radboudumc 14: Tumours of the digestive tract RIMLS: Radboud Institute for Molecular Life Sciences, Mutation, Human Genetics - Radboud University Medical Center, Female, Health Evidence - Radboud University Medical Center
CLINICAL-OUTCOMES, Heterozygote, SURGERY, Ovariectomy, Radboudumc 17: Women's cancers RIHS: Radboud Institute for Health Sciences, Salpingo-oophorectomy, Radboud University Medical Center, NEOPLASIA, MUTATION CARRIERS, OVARIAN-CANCER, Gynaecology - Radboud University Medical Center, SDG 3 - Good Health and Well-being, BREAST-CANCER, Fallopian Tube Neoplasms, Humans, Haematology - Radboud University Medical Center, Peritoneal Neoplasms, TUBAL INTRAEPITHELIAL CARCINOMA, Ovarian Neoplasms, SEROUS CARCINOMA, Pathology - Radboud University Medical Center, WOMEN, BRCA1, Cystadenocarcinoma, Serous, IQ Healthcare - Radboud University Medical Center, Radboudumc 14: Tumours of the digestive tract RIMLS: Radboud Institute for Molecular Life Sciences, Mutation, Human Genetics - Radboud University Medical Center, Female, Health Evidence - Radboud University Medical Center
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