Endometrial pathology and surgical extent in ovarian adult granulosa cell tumor: associations with stage and survival

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BACKGROUND: Adult granulosa cell tumor is a rare ovarian cancer with less aggressive behavior than epithelial ovarian cancer. However, recurrence occurs in up to 30% of patients and is challenging to manage, as treatment options are limited. Additionally, adult granulosa cell tumor has been linked to synchronous endometrial pathology, including endometrial hyperplasia and cancer, but the impact of these abnormalities on surgical decision-making and survival outcomes remains unclear. OBJECTIVE: To evaluate how coexisting endometrial abnormalities influence surgical management and overall survival, and to examine the association between surgical extent (conservative vs complete staging) and recurrence in patients with adult granulosa cell tumor. STUDY DESIGN: This retrospective cohort study included all patients diagnosed with histologically confirmed ovarian adult granulosa cell tumor in Denmark between January 2007 and December 2021. Analyses were first conducted in the comprehensive nationwide Danish cohort, and results were subsequently compared in a combined analysis including data from a Dutch adult granulosa cell tumor cohort (January 2000-December 2021). Surgical procedures were categorized as complete staging (including hysterectomy, bilateral salpingo-oophorectomy, omental and peritoneal biopsies, and peritoneal washings) or less extensive surgery with clinical staging. Abnormal uterine bleeding and endometrial pathology were identified, and their associations with surgical extent and International Federation of Gynecology and Obstetrics stage were assessed. Progression-free survival was compared with surgical extent and International Federation of Gynecology and Obstetrics stage. RESULTS: A total of 252 Danish and 195 Dutch patients (n=447) were included, with median follow-up times of 7.2 and 3.2 years, and recurrence rates of 18% and 42%, respectively. In the Danish cohort, abnormal uterine bleeding and endometrial hyperplasia were associated with receiving less extensive surgery (odds ratio=0.35, 95% confidence interval: 0.18-0.66 and odds ratio=0.39, 95% confidence interval: 0.19-0.76). Furthermore, abnormal uterine bleeding, endometrial hyperplasia, and endometrial cancer were each associated with lower International Federation of Gynecology and Obstetrics stage at diagnosis of adult granulosa cell tumor (odds ratio=0.32, 95% confidence interval: 0.15-0.64; odds ratio=0.28, 95% confidence interval: 0.12-0.6; and odds ratio=0.16, 95% confidence interval: 0.01-0.94, respectively). In the Danish cohort, overall survival was not affected by endometrial cancer (hazard ratio=0.8, 95% confidence interval: 0.21-3.16). No difference in progression-free survival was observed between patients undergoing complete staging and those managed conservatively (hazard ratio=1.37, 95% confidence interval: 0.65-2.88). International Federation of Gynecology and Obstetrics stage IC (hazard ratio=9.4, 95% confidence interval: 4.0-22.29) and stage II-III (hazard ratio=8.4, 95% confidence interval: 2.9-24.17) had higher rates of recurrences compared with those with International Federation of Gynecology and Obstetrics stage IA or IB. Analyses of the combined Danish and Dutch cohorts demonstrated estimates consistent with those observed in the Danish cohort. CONCLUSION: The presence of abnormal uterine bleeding, endometrial hyperplasia, and endometrial cancer was associated lower International Federation of Gynecology and Obstetrics stage, suggesting that these factors facilitate earlier detection of adult granulosa cell tumor without adversely affecting overall survival. Complete surgical staging is not associated with improved progression-free survival in patients with adult granulosa cell tumor. Higher International Federation of Gynecology and Obstetrics stage (IC or higher) was, as expected, associated with an increased rate of recurrence compared to stage IA and IB.

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