Evaluating the risk of ovarian cancer before surgery using the ADNEX model to differentiate between benign, borderline, early and advanced stage invasive, and secondary metastatic tumours: prospective multicentre diagnostic study

Abstract

Objectives: To develop a risk prediction model to preoperatively discriminate between benign, borderline, stage I invasive, stage II-IV invasive, and secondary metastatic ovarian tumours.

Design: Observational diagnostic study using prospectively collected clinical and ultrasound data.

Setting: 24 ultrasound centres in 10 countries.

Participants: Women with an ovarian (including para-ovarian and tubal) mass and who underwent a standardised ultrasound examination before surgery. The model was developed on 3506 patients recruited between 1999 and 2007, temporally validated on 2403 patients recruited between 2009 and 2012, and then updated on all 5909 patients.

Main outcome measures: Histological classification and surgical staging of the mass.

Results: The Assessment of Different NEoplasias in the adneXa (ADNEX) model contains three clinical and six ultrasound predictors: age, serum CA-125 level, type of centre (oncology centres v other hospitals), maximum diameter of lesion, proportion of solid tissue, more than 10 cyst locules, number of papillary projections, acoustic shadows, and ascites. The area under the receiver operating characteristic curve (AUC) for the classic discrimination between benign and malignant tumours was 0.94 (0.93 to 0.95) on temporal validation. The AUC was 0.85 for benign versus borderline, 0.92 for benign versus stage I cancer, 0.99 for benign versus stage II-IV cancer, and 0.95 for benign versus secondary metastatic. AUCs between malignant subtypes varied between 0.71 and 0.95, with an AUC of 0.75 for borderline versus stage I cancer and 0.82 for stage II-IV versus secondary metastatic. Calibration curves showed that the estimated risks were accurate.

Conclusions: The ADNEX model discriminates well between benign and malignant tumours and offers fair to excellent discrimination between four types of ovarian malignancy. The use of ADNEX has the potential to improve triage and management decisions and so reduce morbidity and mortality associated with adnexal pathology.

Conflict of interest statement

Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

© Van Calster et al 2014.

Figures

Fig 1 Calibration plots of predicted probabilities for each type of tumour. Data have been calculated using validation data (n=2403). Plots show how well the predicted probabilities (x axis) agree with observed probabilities (y axis). For perfect agreement, the calibration curve falls on the ideal diagonal line. Histograms below plots show distribution of predicted probabilities

Fig 2 Discrimination plot of ADNEX model after it was updated on pooled dataset (n=5909). For each predicted tumour type, box plots of probabilities are presented for each confirmed tumour type (reference standard). Red vertical lines show baseline probabilities for each type of tumour. For example, the baseline probability of a benign tumour is 0.681; for most women with a benign tumour the predicted probability of a benign tumour was higher than 0.9, whereas most women with an ovarian malignancy (most notably stage II-IV cancer) had clearly lower predicted probabilities of a benign tumour