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. 2017 Sep;146(3):491-497.
doi: 10.1016/j.ygyno.2017.06.008. Epub 2017 Jun 16.

Impact of ascites volume on clinical outcomes in ovarian cancer: A cohort study

J Brian Szender  1 , Tiffany Emmons  2 , Sarah Belliotti  3 , Danielle Dickson  3 , Aalia Khan  1 , Kayla Morrell  4 , A N M Nazmul Khan  5 , Kelly L Singel  2 , Paul C Mayor  1 , Kirsten B Moysich  6 , Kunle Odunsi  7 , Brahm H Segal  8 , Kevin H Eng  4
Affiliations

Impact of ascites volume on clinical outcomes in ovarian cancer: A cohort study

J Brian Szender et al. Gynecol Oncol. 2017 Sep.

Abstract

Objectives: To investigate the impact of ascites volume on ovarian cancer outcomes.

Methods: Clinicopathologic features of a cohort of patients with ovarian cancer were obtained from a curated database at a single institution. Progression free survival (PFS) and overall survival (OS) were recorded. Ascites volume at primary surgery was dichotomized at 2000mL and comparisons for high and low volume ascites were made. Additionally, to elucidate interactions between ascites and ovarian tumor progression, we evaluated the effect of intraperitoneal administrations of murine cell-free ascites versus saline in a syngeneic mouse model of epithelial ovarian cancer.

Results: Out of 685 patients identified, 58% had ascites present at the time of initial surgery. Considering the volume of ascites continuously, each liter of ascites was associated with shorter PFS (HR=1.12, 95% CI: 1.07-1.17) and OS (HR=1.12, 95%CI: 1.07-1.17). Patients with ascites greater than the median of 2000mL had significantly shorter PFS (14.5months vs. 22.7months; p<0.001) and OS (27.7months vs. 42.9months; p<0.001). After adjusting for stage, presence of ascites was inversely associated with ability to achieve optimal cytoreductive surgery. Consistent with these correlative results in patients, intraperitoneal administrations of murine cell-free ascites accelerated ovarian cancer progression in mice.

Conclusions: The volume of ascites at initial diagnosis of ovarian cancer correlated with worse PFS and OS. The effect of large volume on prognosis is likely to be in part related to reduced likelihood for complete resection of tumor (R0). If these findings are confirmed in independent studies, consideration should be made to add the presence of large volume ascites at diagnosis to the staging criteria for ovarian cancer.

Keywords: Ascites; Biomarkers; Ovarian cancer; Prognosis; Tumor microenvironment.

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Figures

Figure 1
Figure 1. Volume of ascites at initial diagnosis of ovarian cancer correlates with worse PFS and OS
Kaplan-Meier analysis of progression free (PFS) and overall (OS) survival, stratified by ascites volume at the time of diagnosis. Patients with no ascites had the best prognosis, while those with ≤ 2000 mL had a better prognosis than those with > 2000 mL
Figure 2
Figure 2. Ascites volume at primary surgery projects predicts progress-free and overall survival
Modeled survival prediction was analyzed as a function of ascites volume (L). Considering the volume of ascites continuously, each liter of ascites was associated with shorter PFS and OS. The margin between predicted PFS and OS remained static across a large range of ascites volumes.
Figure 3
Figure 3. Intraperitoneal administrations of cell-free ascites accelerate ovarian cancer progression in mice
Mice were administered intraperitoneal syngeneic epithelial ovarian cancer cells expressing luciferase (Luc+MOSEC), followed by intraperitoneal administration of cell-free ascites or PBS on days 4, 7, and 11. A. Mice administered cell-free ascites had an increased bioluminescent signal on day 18, a marker of greater tumor burden (p =0.034). B. Ascites administration decreased time to morbidity requiring euthanasia (p=0.009). Data are from 10 mice per treatment group and are representative of two separate experiments.
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