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Pre-operative prediction of residual disease after interval cytoreduction for epithelial ovarian cancer using HE4
  1. Pien Lof1,
  2. Roelien van de Vrie1,
  3. Catharina M Korse2,
  4. Willemien J van Driel1,
  5. Mignon D J M van Gent3,
  6. Mona A Karlsen4,
  7. Frederic Amant1,3 and
  8. Christianne A R Lok1
  1. 1Center for Gynecologic Oncology Amsterdam, Netherlands Cancer Institute, Amsterdam, The Netherlands
  2. 2Department of Laboratory Medicine, Netherlands Cancer Institute, Amsterdam, The Netherlands
  3. 3Center for Gynecologic Oncology Amsterdam, Amsterdam University Medical Centres, Amsterdam, The Netherlands
  4. 4Department of Gynecology, Copenhagen University Hospital, Kobenhavn, Denmark
  1. Correspondence to Pien Lof, Department of Gynecology, Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands; p.lof{at}


Background Presence of residual disease after cytoreductive surgery is an important negative prognostic factor for patients with advanced stage epithelial ovarian cancer. Surgery is of limited benefit when the diameter of residual disease is >1 cm. Residual disease is difficult to predict before surgery. The multivariate model Cancer Ovarii Non-invasive Assessment of Treatment Strategy (CONATS) index, based on serum biomarker HE4, age, and World Health Organization performance status, predicted no visible residual disease in patients undergoing primary cytoreductive surgery with an area under the curve (AUC) of 0.85. The AUC of predicting residual disease >1 cm was not reported, although this can be of importance for pre-operative decision making, especially in fragile patients. We tested this model for predicting residual disease >1 cm in patients undergoing interval cytoreduction.

Methods We retrospectively included patients with advanced epithelial ovarian cancer who underwent interval cytoreduction between January 2010 and December 2017 in two tertiary centers in the Netherlands. HE4 was measured with electrochemiluminescence in pre-operative samples. The CONATS index was used to predict residual disease. AUCs were calculated to predict residual disease >1 cm.

Results A total of 273 patients were included. Mean (SD) age was 64 (11) years. Median number of cycles of neoadjuvant chemotherapy was 3 (range 3–6) and the most common regimen used consisted of carboplatin and paclitaxel. Before interval cytoreduction, 19 patients (7%) showed complete response to chemotherapy, 251 patients (92%) showed partial response, and 3 patients (1%) showed stable disease at imaging. Following surgery, 232 patients (85%) had residual disease ≤1 cm and 41 patients (15%) had residual disease >1 cm. The AUC was 0.80 for predicting residual disease >1 cm. In patients ≥70 years of age the AUC was 0.82.

Conclusion The CONATS index predicts surgical outcome after interval cytoreduction and is useful in counseling patients about the chance of whether an optimal interval cytoreduction can be achieved. This could be especially helpful in counseling elderly patients in whom surgery has a high risk of complications.

  • ovarian cancer
  • surgical procedures, operative

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  • PL and RvdV contributed equally.

  • Contributors Concept and design: PL, RvdV, CK, MK, CL. Data collection and data analyses: PL, RvdV, CK and CL. Writing manuscript: all authors.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement All data relevant to the study are included in the article or uploaded as supplementary information.