Impact of cytoreductive surgery on survival outcomes for recurrent adult-type granulosa cell tumors of the ovary.
Authors: How Jeffrey , Flores Legarreta Alejandra , Fellman Bryan M. , Handley Katelyn , Foster Katherine , Glassman Deanna , Lawson Barrett , Ramondetta Lois M. , Gershenson David Marc , Sood Anil K , Hillman Robert Tyler 
Published: June 2023

5573 Background: Adult-type granulosa cell tumor of the ovary (aGCT) is a rare tumor that often relapses and the optimal management strategy is not known. Cytoreductive surgery (CRS) offers an attractive option for disease confined to the abdomen/pelvis. However, few studies have evaluated the role of CRS compared to systemic therapy alone. Thus, the study objective was to determine the impact of secondary, tertiary, and quaternary CRS on survival outcomes for patients with relapsed aGCT. Methods: This was an IRB-approved retrospective cohort study that evaluated all patients with relapsed aGCT who were enrolled in the Rare Gynecologic Malignancy Registry at MD Anderson. Study inclusion criteria were patients who had histology-proven aGCT, were above 18 years of age, had at least one documented relapse, and had received treatment or treatment planning at MD Anderson. Progression-free survival (PFS) endpoints were the outcomes of interest and were defined as follows: PFS2 was defined from first recurrence to subsequent progression or death (PFS2), PFS3 was defined as second relapse/progression to third relapse/progression or death, and PFS4 was similarly defined. PFS2, PFS3, and PFS4 were estimated with methods of Kaplan and Meier and were modeled via cox proportional hazards regression. Analyses were performed among those with resectable disease at time of disease progression. Results: Among the 369 aGCT patients identified from January 1970 to October 2022, 162 met the study inclusion criteria for analysis. The mean age of diagnosis was 44.4 years old and the majority were initially diagnosed with stage 1 disease (72.8%). The median follow-up time for all patients was 5.86 years (range 0.09 – 34.27). At the first relapse, there were 151 patients who had resectable disease with 128 who underwent secondary CRS. PFS2 was significantly improved among those who underwent CRS compared to those who did not (HR 0.50, 95% CI 0.30 – 0.81; p = 0.005) with the median PFS2 difference being 18.24 months (p = 0.006). At the second relapse/progression, there were 120 patients with resectable disease with 52 who underwent tertiary CRS. PFS3 was significantly improved among those who underwent CRS compared to those who did not (HR 0.57, 95% CI 0.39 – 0.84; p = 0.004) with the median PFS3 difference being 6 months (p = 0.01). At the third relapse/progression, there were 96 patients with resectable disease with 46 who underwent quaternary CRS. There was a trend towards improved PFS3 among those who underwent CRS compared to those who did not (HR 0.69, 95% CI 0.45 – 1.06; p = 0.09). The use of systemic or hormonal therapy did not confer additional PFS benefit among those who underwent CRS. Conclusions: For relapsed, resectable aGCT, CRS may offer a beneficial impact on PFS. Future studies should evaluate the role of CRS on survival outcomes.