Tumor Biology

, Volume 37, Issue 9, pp 12619–12626 | Cite as

A novel index for preoperative, non-invasive prediction of macro-radical primary surgery in patients with stage IIIC–IV ovarian cancer—a part of the Danish prospective pelvic mass study

  • Mona Aarenstrup Karlsen
  • Carsten Fagö-Olsen
  • Estrid Høgdall
  • Tine Henrichsen Schnack
  • Ib Jarle Christensen
  • Lotte Nedergaard
  • Lene Lundvall
  • Magnus Christian Lydolph
  • Svend Aage Engelholm
  • Claus Høgdall
Original Article


The purpose of this study was to develop a novel index for preoperative, non-invasive prediction of complete primary cytoreduction in patients with FIGO stage IIIC–IV epithelial ovarian cancer. Prospectively collected clinical data was registered in the Danish Gynecologic Cancer Database. Blood samples were collected within 14 days of surgery and stored by the Danish CancerBiobank. Serum human epididymis protein 4 (HE4), serum cancer antigen 125 (CA125), age, performance status, and presence/absence of ascites at ultrasonography were evaluated individually and combined to predict complete tumor removal. One hundred fifty patients with advanced epithelial ovarian cancer were treated with primary debulking surgery (PDS). Complete PDS was achieved in 41 cases (27 %). The receiver operating characteristic curves demonstrated an area under the curve of 0.785 for HE4, 0.678 for CA125, and 0.688 for age. The multivariate model (Cancer Ovarii Non-invasive Assessment of Treatment Strategy (CONATS) index), consisting of HE4, age, and performance status, demonstrated an AUC of 0.853. According to the Danish indicator level, macro-radical PDS should be achieved in 60 % of patients admitted to primary surgery (positive predictive value of 60 %), resulting in a negative predictive value of 87.5 %, sensitivity of 68.3 %, specificity of 83.5 %, and cutoff of 0.63 for the CONATS index. Non-invasive prediction of complete PDS is possible with the CONATS index. The CONATS index is meant as a supplement to the standard preoperative evaluation of each patient. Evaluation of the CONATS index combined with radiological and/or laparoscopic findings may improve the assessment of the optimal treatment strategy in patients with advanced epithelial ovarian cancer.


Ovarian cancer HE4 Primary debulking surgery Neoadjuvant chemotherapy Multidisciplinary team meetings Non-invasive prediction model 



We thank the Danish CancerBiobank (DCB) for providing blood samples collected, handled, and stored according to strict biobank guidelines.

We furthermore thank the Danish Gynecologic Cancer Database (DGCD) for providing clinical data for the article.

Finally, we thank Abbott Diagnostics for providing kits for serum HE4 analyses.

Compliance with ethical standards

Oral and written consent was given by each patient before enrollment. The Danish Ethical Committee has approved the study protocol (KF01-227/03 and KF01-143/04, H-3-2010-022).

Sources of support

This study was supported by the Arvid Nilsson Foundation, the Research Council at Herlev University Hospital, the Gangsted foundation, Merchant Kristian Kjær and wife Margrethe Kjær Foundation, and Director Jacob Madsen and wife Olga Madsen Foundation.

Furthermore, Abbott Diagnostics provided the HE4 kits for serum analyses.

Conflicts of interest



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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2016

Authors and Affiliations

  • Mona Aarenstrup Karlsen
    • 1
    • 2
  • Carsten Fagö-Olsen
    • 1
  • Estrid Høgdall
    • 2
  • Tine Henrichsen Schnack
    • 1
  • Ib Jarle Christensen
    • 2
  • Lotte Nedergaard
    • 3
  • Lene Lundvall
    • 1
  • Magnus Christian Lydolph
    • 4
  • Svend Aage Engelholm
    • 5
  • Claus Høgdall
    • 1
  1. 1.Gynecologic ClinicUniversity Hospital of Copenhagen, RigshospitaletCopenhagenDenmark
  2. 2.Molecular Unit, Department of PathologyHerlev University HospitalHerlevDenmark
  3. 3.Department of PathologyUniversity Hospital of Copenhagen, RigshospitaletCopenhagenDenmark
  4. 4.Department of Autoimmunology and BiomarkersStatens Serum InstituteCopenhagenDenmark
  5. 5.Department of Radiation OncologyUniversity Hospital of Copenhagen, RigshospitaletCopenhagenDenmark

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