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

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 METHODS Unpublished data from three centers were supplemented by studies identified in a systematic review of EMBASE, MEDLINE, and the Cochrane library describing women with a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.

Incidence of pelvic high-grade serous carcinoma after isolated STIC diagnosis: A systematic review of the literature

“…During the preparation of the manuscript, Steenbeek and colleagues published a systematic review about the risk of peritoneal carcinomatosis after RRSO with similar results in February 2022. They report a five- and ten- year- risk of developing peritoneal carcinomatosis of 10.5% and 27.5% after RRSO, respectively ( 37 ). Due to the prior closure of our data collection, we could not include their newly published STIC cases.…”

Risk of Peritoneal Cancer After Risk-Reducing Bilateral Salpingo-Oophorectomy for Women With Germline BRCA Pathogenic Variants: A Cause for Concern or Potentially Avoidable?

“…Indeed, evolutionary analyses have suggested a window of 7 years between the development of a STIC and initiation of an invasive cancer. 16 The median time between rrBSO and diagnosis of peritoneal carcinomatosis in women with STIC in the study by Steenbeek et al 10 was 48 months (range, 18-118 months), which would support this hypothesis. In addition, two BRCA1 PV carriers had identical TP53 somatic mutations in their isolated STIC and subsequent peritoneal carcinomatosis that developed many years later, suggesting clonal evolution.…”

“…7 However, there is a small residual risk (1%-4%) for peritoneal carcinomatosis after risk-reducing bilateral salpingo-oophorectomy (rrBSO), which should be discussed during counseling before surgery. 8,9 In the article that accompanies this editorial, Steenbeek et al 10 show that the presence of STIC at the time of rrBSO was strongly associated with the subsequent development of peritoneal carcinomatosis in BRCA1 and BRCA2 PV carriers. Diagnostic criteria for STIC are based on tubal morphology, abnormal p53 immunohistochemical staining, and high Ki67 staining.…”

“…In the article that accompanies this editorial, Steenbeek et al 10 show that the presence of STIC at the time of rrBSO was strongly associated with the subsequent development of peritoneal carcinomatosis in BRCA1 and BRCA2 PV carriers. Diagnostic criteria for STIC are based on tubal morphology, abnormal p53 immunohistochemical staining, and high Ki67 staining.…”

Serous tubal intra‐epithelial carcinoma: what do we really know at this point?

“…However, in a recent metaanalysis by Steenbeek et al, which included 115 women with STIC, the estimated 5-and 10-year risks of peritoneal carcinoma were 11 and 28%, respectively. 105 In that study, the exact level to which STICs were stringently diagnosed and whether it was possible to definitively exclude a concurrent highgrade serous carcinoma in all cases at the time of salpingectomy are unclear. Larger and carefully designed studies are needed to reproduce these results.…”