Sophie Schoenen

Evaluation of risk-reducing radical fimbriectomy followed by delayed oophorectomy in high-risk Women: A single-center retrospective study

Ovarian carcinoma is a leading cause of cancer-related mortality in women. Approximately 20 % of cases are hereditary, mainly BRCA mutations. Current clinical guidelines recommend bilateral salpingo-oophorectomy between ages 35-45 for high-risk individuals, leading to premature menopause. Given evidence supporting the tubal origin of most ovarian cancers, radical fimbriectomy followed by delayed oophorectomy may offer a menopause-sparing alternative for women refusing early ovariectomy. To evaluate the oncologic safety and clinical outcomes of this two-step risk-reducing strategy. This retrospective single-center study included all high-risk premenopausal women who had completed childbearing, declined BSO and underwent radical fimbriectomy between 2014 and 2022. The primary outcome was the incidence of ovarian or pelvic cancer following radical fimbriectomy, estimated using the Kalbfleisch-Prentice method. Secondary outcomes included surgical complications, tubal lesions, menopause onset, breast cancer incidence and delayed oophorectomy rate. A total of 132 women were included; 62.9 % had BRCA1, 25.8 % BRCA2, and 11.3 % other high-risk mutations (RAD51C, PALB2). No tubal lesions were found in 121 cases (91.7 %), while 11 (8.3 %) had abnormalities: one high-grade serous carcinoma, six serous tubal intraepithelial carcinoma, and four minor lesions. After a median 30.4-month follow-up, no high-grade serous carcinoma was reported. Delayed bilateral oophorectomy was performed in 24 women (18.5 %), and menopause occurred in 27 at a median age of 45. One pregnancy occurred post-fimbriectomy via assisted reproductive technology. Radical fimbriectomy with delayed oophorectomy may be a safe and feasible option for high-risk women seeking to avoid early menopause. Longer-term prospective studies are needed.

Presence of atypical extravillous trophoblast foci is an independent predictor of the risk of progression to postmolar neoplasia

Amongst complete hydatidiform moles, 15% to 20% will progress to postmolar neoplasia. Scientists have long searched for routinely applicable prognostic markers that can efficiently predict the risk of postmolar neoplasia. To assess the prognostic value of atypical extravillous trophoblast foci within complete hydatidiform moles on the development of postmolar gestational trophoblastic neoplasia. Between January 2017 and December 2022, a retrospective multicenter study was conducted in the Belgian Gestational Trophoblastic Diseases Registry (French-speaking center). All complete hydatidiform moles were included after being confirmed by a systematic centralized pathological review in 3 academic units with a high exposure to placental pathology. Postmolar gestational trophoblastic neoplasia was diagnosed according to the International Federation of Gynecology and Obstetrics 2000 criteria. Atypical extravillous trophoblast foci were defined as trophoblastic clusters in the intervillous chamber with a biphasic pattern of mononucleated cytotrophoblasts and multinucleated syncytiotrophoblasts. Their prognostic value for the development of postmolar gestational trophoblastic neoplasia was assessed using univariate analysis, followed by a multivariate model with stepwise selection of variables having a P value below .10 in the univariate analysis. A risk score, the "R-score," was developed based on the most significant variables of the multivariate model. The intercept and coefficients were obtained by fitting a logistic regression model. To facilitate its use in clinical practice, we established a score ranging from 0 to 10. Of the 216 patients with complete hydatidiform mole, 56 patients subsequently developed postmolar gestational trophoblastic neoplasia (25.9%). Atypical extravillous trophoblast foci were found in 105/216 cases (48.6%). The risk of postmolar neoplasia was significantly associated with the presence of this pathological feature in univariate analysis (odds ratio, 2.93, P=.0010) and in multivariate logistic regression adjusted for confounding variables (odds ratio, 2.34, P=.0152). The R-score is based on the presence of atypical extravillous trophoblast foci, age, and postevacuation human chorionic gonadotropin levels, with an area under the curve of 0.721. A score below 6 indicates a low risk of postmolar neoplasia (15%), while a score of 7 or higher indicates a high risk (42%). The presence of atypical extravillous trophoblast into complete moles is associated with the risk of developing postmolar gestational trophoblastic neoplasia. These foci may represent a new inexpensive and widely available histological prognostic marker.

Chemotherapy is not needed when complete evacuation of gestational choriocarcinoma leads to hCG normalization

The standard treatment for gestational choriocarcinoma is chemotherapy. To describe the risk of recurrence with expectant management of gestational choriocarcinoma that has reached a normal human chorionic gonadotropin level after tumor removal without adjuvant chemotherapy. A retrospective multicenter international cohort study was conducted from 1981 to 2017 involving 11 gestational trophoblastic disease reference centers with patient's follow-up extended until 2023. Clinical and biological data of included patients were extracted from each center's database. The inclusion criteria were i) histological diagnosis of gestational choriocarcinoma in any kind of placental tissue retrieved, ii) spontaneous normalization of human chorionic gonadotropin level following choriocarcinoma retrieval, iii) patient did not receive any oncological treatment for the choriocarcinoma, iv) and at least 6 months of follow-up after the first human chorionic gonadotropin level normalization. Among 80 patients with retrieved gestational choriocarcinoma and whose human chorionic gonadotropin level normalized without any other oncological therapy, none had a recurrence of choriocarcinoma after a median follow-up of 50 months. The median interval between choriocarcinoma excision and human chorionic gonadotropin level normalization was 48 days. The International Federation of Gynecology and Obstetrics/World Health Organization risk score was ≤6 in 93.7% of the cases. This multicenter international study reports that selected patients with gestational choriocarcinoma managed in gestational trophoblastic disease reference centers did not experience any relapse when the initial tumor evacuation is followed by human chorionic gonadotropin level normalization without any additional treatment. Expectant management may be a safe approach for highly selected patients.

Impact of atypical extra-villous trophoblast foci on the natural history and management of post-molar gestational trophoblastic neoplasia

Approximately 15% to 20% of complete hydatidiform moles progress to post-molar gestational trophoblastic neoplasia. The presence of atypical extra-villous trophoblast foci, described in complete hydatidiform moles, has been associated with an increased risk of developing post-molar gestational trophoblastic neoplasia. The primary objective of this study was to evaluate the predictive value of atypical extra-villous trophoblast foci for treatment response in post-molar gestational trophoblastic neoplasia. Secondary objectives were to assess the clinical impact of these foci on disease characteristics, the International Federation of Gynecology and Obstetrics (FIGO) score, disease stage, and human chorionic gonadotropin (hCG) kinetics. A retrospective multi-center study was conducted by the Belgian Gestational Trophoblastic Diseases Registry (French-speaking center) between January 2017 and December 2022. All cases of complete hydatidiform mole were centrally reviewed by expert pathologists specialized in placental pathology from 3 university hospitals. Post-molar gestational trophoblastic neoplasia was diagnosed according to FIGO 2000 criteria. Clinical features were compared according to the presence or absence of atypical trophoblast foci. Among 216 patients diagnosed with complete hydatidiform mole, 56 (26%) developed post-molar gestational trophoblastic neoplasia. Atypical extra-villous trophoblast foci were identified in 38 of 56 (68%) cases. Baseline demographic characteristics, including age, were comparable between the 2 groups. Patients with atypical foci more frequently had FIGO scores ≥6 (p =.044) and pulmonary metastases (18.4% vs 5.6%). All patients requiring multi-agent chemotherapy belonged to the atypical foci group (p =.073). Pre-treatment hCG nadir levels were higher, and hCG slopes steeper in the atypical group (p =.0027 and p =.0052). Post-molar gestational trophoblastic neoplasia arising from complete hydatidiform moles with atypical extra-villous trophoblast foci is more frequently associated with an unfavorable prognosis and the need for multi-agent chemotherapy than disease arising from moles without atypical foci.