Rosalba Portuesi

Adult ovarian granulosa cell tumors: analysis of outcomes and risk factors for recurrence

Adult granulosa cell tumors represent less than 5% of all ovarian malignancies. The aim of this study was to analyze the clinicopathological parameters and their impact on progression-free and overall survival. Patients with primary adult granulosa cell tumors treated in three international referral centers between July 1999 and December 2018 were included. The following data were anonymously exported from the prospective database: age at diagnosis, International Federation of Gynecology and Obstetrics (FIGO) stage, adjuvant therapy, surgical procedures, progression-free survival, and overall survival. Descriptive statistical analysis regarding tumor and treatment characteristics was performed. Survival analyses included Kaplan-Meier functions and Cox proportional hazard ratios (HR). A total of 168 patients with primary adult granulosa cell tumors were included. Median age was 50 years (range 13-82). With regard to stage distribution, 54.2% (n=91) of patients were FIGO stage IA, 1.2% (n=2) were stage IB, 26.8% (n=45) were stage IC, and 17.9% (n=30) were FIGO stage II-IV. 66.7% (n=112) of patients underwent surgical restaging, of whom 17.9% (n=20) were moved to a higher stage. In addition, 36 (21.4%) patients underwent fertility-sparing surgery. After a median follow-up of 61 months (range 0-209), 10.7% of patients (n=18) had recurrent disease and 4.8% (n=8) died of disease. Five-year progression-free survival was 86.1% and estimated overall survival was 95.7%. Five-year progression-free survival was worse for patients with advanced stages (FIGO stage IA/B vs IC: HR 5.09 (95% CI 1.53 to 16.9); FIGO stage IA/B vs II-IV: HR 5.62 (95% CI 1.58 to 19.9)). Nineteen patients receiving adjuvant chemotherapy had lower estimated 5-year progression-free survival compared with patients not receiving chemotherapy (49.7% vs 91.1%, p<0.001; HR 9.15 (95% CI 3.62 to 23.1)). The prognosis of patients with primary adult granulosa cell tumors is mainly determined by FIGO stage. The outcome of patients with FIGO stage IC is comparable to those with advanced stages. Fertility-sparing surgery seems to be a safe procedure in stage IA. Our data do not support the use of adjuvant chemotherapy in early and advanced stages of adult granulosa cell tumors.

Role of inhibin B in detecting recurrence of granulosa cell tumors of the ovary in postmenopausal patients

Several biomarkers have been proposed for the detection of recurrences in adult-type granulosa cell tumors of the ovary. Here we validate the value of inhibin B in detecting recurrences and investigate its role in guiding follow-up examinations and treatment strategies in postmenopausal patients with ovarian adult-type granulosa cell tumors. Data from 140 patients with a diagnosis of adult-type granulosa cell tumor of the ovary referred to the European Institute of Oncology of Milan from January 1996 to March 2016 were retrospectively collected. Among these, we selected data from 47 postmenopausal women for whom serial inhibin B measurements and related imaging examinations were performed according to the follow-up program, with a total of 315 serum inhibin B samples, together with the corresponding clinical examination, and 180 imaging examinations, confirming the presence or absence of macroscopic disease. At a cut-off of 7 pg/mL, inhibin B levels were significantly correlated with the presence/absence of disease (p<0.01), with a sensitivity of 98.8% (95% confidence interval (CI) 95.8% to 99.9%) and a specificity of 88.9% (95% CI 82.6% to 93.5%). Further, inhibin B was positively correlated with the size of the lesion, and levels were significantly higher in patients with larger lesions also at a cut-off size of 3 cm (total diameter). Logistic regression showed that 15.6 pg/mL, 44.6 pg/mL, and 73.6 pg/mL inhibin B corresponded to 25%, 50%, and 75% probability of having an abnormal computer tomography scan, respectively. Our results confirmed that inhibin B is a sensitive and specific marker for adult-type granulosa cell tumors of the ovary that may be used during follow-up for detection of recurrences. Moreover, it could guide clinicians in the decision regarding when to perform imaging, avoiding redundant interventional tests in the absence of clinical suspicion.