Development of Peritoneal Carcinoma in women diagnosed with Serous Tubal Intraepithelial Carcinoma (STIC) following Risk-Reducing Salpingo-Oophorectomy (RRSO)

Abstract

Introduction The management of Serous Tubal Intraepithelial Carcinoma (STIC) found at the time of Risk-Reducing Salpingo-Oophorectomy (RRSO) remains unclear. We set out to analyse the incidence of peritoneal carcinomas developed after prophylactic surgery and to formulate further guidance for these patients. Methods This is a retrospective study of 300 consecutive RRSO performed at the Royal Marsden Hospital between January 2008 and January 2017. Results The median age at RRSO was 47.8 years (range 34 to 60 years) and median BMI was 26.2 kg/m 2 (range 16 to 51 kg/m 2 ). A total of 273 patients (91%) were tested for BRCA mutations. Of these, 124 (45.4%) had a BRCA 1 mutation, 118 (43.2%) had a BRCA 2 mutation, 2 (0.7%) had both a BRCA 1 and a BRCA 2 mutation and 29 (10.6%) had no BRCA mutation detected. Isolated STIC lesions were identified in 7 cases (2.3%) and p53 signatures in 75 cases (25%). There were five (1.6%) incidental tubal carcinomas and one (0.3%) ovarian carcinoma at the time of surgery. Two (28.6%) of the 7 patients with STIC identified following RRSO had high grade serous peritoneal carcinoma diagnosed at 53 and 75 months. One (0.3%) patient from the other 287 patients from our series with no STIC diagnosis or incidental carcinomas at RRSO developed high grade serous carcinoma of peritoneal origin after 92 months. Conclusion This study demonstrates that when a STIC lesion is identified following RRSO there is a significantly higher risk of a subsequent peritoneal cancer. Although there is no published consensus in literature, we recommend that consideration should be given for long term follow-up if a STIC lesion is identified at RRSO.

Pathological findings following risk-reducing salpingo-oophorectomy in BRCA mutation carriers: A systematic review and meta-analysis

“…However, staging and follow-up data are limited. In a large cohort, long-term follow-up was recommended if an STIC lesion was identified at RRSO [89]. The role of adjuvant therapy in the management of STIC remains elusive [87].…”

Specialist oncological surgery for removal of the ovaries and fallopian tubes in BRCA1 and BRCA2 pathogenic variant carriers may reduce primary peritoneal cancer risk to very low levels

“…24 However, cancer prevention strategies through RRBSO remain the first-line management approach, as PARP inhibitors are not curative due to the development of chemoresistance. The absence of occult lesions and postsurgical PPCs in those undergoing RRBSO before the risk period (n = 203) lends support to early RRBSO if a woman has completed her family 18 even though this may not now reduce breast cancer risk particularly in BRCA1 carriers. 25,26 The low level of PPC in the specialty series fits well with the concept that most PPC derives from fimbrial STIC cells that get displaced from the fimbrial ends of the fallopian tubes into the peritoneal cavity.…”

“…27,28 Further assessment of PPC risk after RRBSO in BRCA1/2 PV carriers where STIC lesions were identified may justify some sort of an intervention, such as staging CT scan to exclude metastatic disease or even a course of PARP inhibitor treatment if substantial rates continue to be reported. 18 Certainly a more vigilant follow-up may be justified. We are only aware of two STIC lesions in our series without microinvasion, and this low rate may reflect the earlier surgery particularly in more recent years with RRBSO driven by presymptomatic testing in BRCA1/2 families.…”

“…17 Indeed, the presence of STIC lesions was predictive of future PPC in one single institution study with 2 of 7 (28.6%) developing subsequent PPC compared to only 1 of 287 (0.3%) without STIC. 18 The theory regarding potential prevention of ovarian/tubal cancers by removal of the fallopian tubes has resulted in a number of pilot studies to assess the potential benefits of early tubal surgery and delayed oophorectomy to mitigate the effects of early surgical menopause on subsequent health and quality of life. 19,20 We have previously published an early series of RRBSO where we noted that there were no cases of PPC following 300 surgeries that included 160 BRCA1/2 PV carriers.…”

Impact of a Structured Early Detection Program on Adherence to Guidelines for Risk-Reducing Surgery in BRCA1/2 Carriers

“…Indeed, of the 31 older patients, 1 was diagnosed with a stage 2 malignancy and 2 were diagnosed with STIC lesions (6.5%), which is a higher rate than 1%-2% reported STIC identification during RRSO. 15,16 Arguably, the one malignancy that may have been prevented with earlier participation in a screening program.…”