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Pooled Analysis of the Prognostic Relevance of Disseminated Tumor Cells in the Bone Marrow of Patients With Ovarian Cancer

Fehm, Tanja MD, PhD*; Banys, Malgorzata MD†‡; Rack, Brigitte MD, PhD§; Janni, Wolfgang MD, PhD; Marth, Christian MD, PhD; Blassl, Christina; Hartkopf, Andreas MD; Trope, Claes MD, PhD#; Kimmig, Rainer MD, PhD**; Krawczyk, Natalia MD*; Wallwiener, Diethelm MD, PhD; Wimberger, Pauline MD, PhD††; Kasimir-Bauer, Sabine PhD**

International Journal of Gynecological Cancer: June 2013 - Volume 23 - Issue 5 - p 839–845
doi: 10.1097/IGC.0b013e3182907109
Ovarian Cancer

Objective: Detection of disseminated tumor cells (DTCs) in the bone marrow (BM) of patients with breast cancer is associated with poor outcomes. Recent studies demonstrated that DTCs may serve as a prognostic factor in ovarian cancer. The aim of this 3-center study was to evaluate the impact of BM status on survival in a large cohort of patients with ovarian cancer.

Materials and Methods: Four hundred ninety-five patients with primary ovarian cancer were included in this 3-center prospective study. Bone marrow aspirates were collected intraoperatively from the iliac crest. Disseminated tumor cells were identified by antibody staining and by cytomorphology. Clinical outcome was correlated with the presence of DTCs.

Results: Disseminated tumor cells were detected in 27% of all BM aspirates. The number of cytokeratin-positive cells ranged from 1 to 42 per 2 × 106 mononuclear cells. Disseminated tumor cell status did correlate with histologic subtype but not with any of the other established clinicopathologic factors. The overall survival was significantly shorter among DTC-positive patients compared to DTC-negative patients (51 months; 95% confidence interval, 37–65 months vs 33 months; 95% confidence interval, 23–43 months; P = 0.023). In the multivariate analysis, BM status, International Federation of Gynecology and Obstetrics stage, nodal status, resection status, and age were independent predictors of reduced overall survival, whereas only BM status, International Federation of Gynecology and Obstetrics stage, and resection status independently predicted progression-free survival.

Conclusions: Tumor cell dissemination into the BM is a common phenomenon in ovarian cancer. Disseminated tumor cell detection has the potential to become an important biomarker for prognostication and disease monitoring in patients with ovarian cancer.

*Department of Gynecology and Obstetrics, University Hospital Düsseldorf, University of Düsseldorf, Germany; †Department of Obstetrics and Gynecology, University of Tuebingen, Germany; ‡Department of Gynecology and Obstetrics, Marienkrankenhaus Hamburg, Germany; §Department of Gynecology and Obstetrics, University Hospital Munich, Ludwig Maximilian University of Munich, Germany; ∥Department of Gynecology and Obstetrics, University Hospital Ulm, University of Ulm, Germany; ¶Department of Obstetrics and Gynecology, Innsbruck Medical University, Innsbruck, Austria; #Gynecologic Department, The Norwegian Radium Hospital, Oslo, Norway; **Department of Gynecology and Obstetrics, University Hospital Essen, University of Duisburg-Essen, Germany; and ††Department of Gynecology and Obstetrics, University Hospital Dresden, University of Dresden, Germany.

Address correspondence and reprint requests to Prof. Tanja Fehm, Head of Department of Obstetrics and Gynecology, University of Düsseldorf, Moorenstr. 5, 40225 Düsseldorf, Germany. E-mail: tanja.fehm@med.uni-tuebingen.de

The present work was partially supported by a grant from the German Research Foundation (Deutsche Forschungsgemeinschaft); grant number: NE804/4-1 (H.N.) und KA1583/3-1 (S. K.-B.). No funding was received from: National Institutes of Health (NIH); Wellcome Trust; Howard Hughes Medical Institute (HHMI).

Tanja Fehm, Malgorzata Banys, and Brigitte Rack contributed equally to this manuscript.

The authors declare no conflicts of interest.

Received January 14, 2013

Accepted March 5, 2013

Copyright © 2013 by IGCS and ESGO