Introduction/Background*After risk-reducing salpingo-oophorectomy (RRSO), there is an approximate 3.9% and 1.9% risk of developing peritoneal carcinomatosis (PC) for BRCA1/2 pathogenic variant carriers, respectively. The origin of PC is yet unknown. However, as the origin of ovarian cancer probably lies in the Fallopian tube, the Serous Tubal Intraepithelial Carcinoma (STIC) may be the origin of PC as well. In this Individual Patient Data Meta-Analysis (IPDMA), we determine the risk of PC for BRCA1/2 pathogenic variant carriers with and without STIC at RRSO.
Methodology We performed a systematic search of MEDLINE, EMBASE and Cochrane on studies providing follow-up in BRCA-mutation carriers after RRSO. Individual patient data was extracted and the authors of eligible studies were contacted to complete this data. Additionally, we retrospectively collected data from the Radboudumc (Nijmegen, the Netherlands), Kaiser Permanente (San Francisco, USA) and MD Anderson (Houston, USA) of BRCA1/2 pathogenic variant carriers undergoing RRSO.
Result(s)*After screening, 15 out of 2.151 studies were included. Including the retrospective case series, individual patient data was available for 3.121 women without STIC and 115 women with STIC at RRSO. The median age (range) was 46 (24-80) of women without and 52 (36-77) for women with STIC. The hazard ratio to develop PC after RRSO was 29.3 for women with STIC compared to women without STIC at RRSO (P<0.001) (figure 1). The five-year risk to develop PC was 0.4% (0.2%-0.7%) for women without STIC and 12.6% (5.2%-19.3%) for women with STIC. The respective ten-year risks are 0.9% (0.3-1.4) and 23.5% (10.6-34.5%). Additional sensitivity analyses did not alter the results.
Conclusion*From this IPDMA we conclude that BRCA pathogenic variant carriers with a STIC at RRSO are at increased risk to develop PC during follow-up. These results are important for clinical awareness and future research. The question arises whether a STIC should be considered as precursor or early stage ovarian cancer. Larger prospective-multicenter studies are needed to investigate the additional value of staging surgery and/or chemotherapy in case of STIC.
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