Whilst patients with ovarian cancer clearly benefit from centralised, comprehensive care in dedicated cancer centres, unfortunately the majority of them still do not receive appropriate specialist treatment. Any improvement in the accuracy of current triaging and referral pathways whether using new imaging tests or biomarkers would therefore be of value in order to optimise the appropriate selection of patients for such care (Chapter 1). An analysis of the current evidence shows that such diagnostic tests are now available, but still await recognition, acceptance and widespread adoption. It is therefore to be hoped that present guidance relating to the classification of ovarian masses will soon become more “evidence-based”. These include the International Ovarian Tumour Analysis (IOTA) LR2 risk prediction model and ultrasound-based IOTA Simple Rules (SR) (Chapter 2). Based on a comprehensive recent meta-analysis both currently offer the optimal “evidence-based” approach to discriminating between cancer and benign conditions in women with adnexal tumours needing surgery (Chapter 3). The IOTA LR2 risk model and SR are reliable diagnostic tests having been shown to maintain a high sensitivity for cancer after independent external validation and both temporal and external validation by the IOTA group in the hands of examiners with various levels of ultrasound expertise (Chapter 4 and 5). Both diagnostic approaches also offer more accurate triage compared to the current standard of care diagnostic test Risk of Malignancy Index (RMI). The development of the IOTA Assessment of Different NEoplasias in the AdneXa (ADNEX) multiclass risk prediction model represents an important step forward towards more individualised patient care in this area (Chapter 6). The ADNEX model is novel and enables the more specific subtyping of adnexal cancers (i.e. borderline tumours, stage 1 invasive ovarian cancer, stage II-IV invasive ovarian cancer, and secondary metastatic malignant tumours) and shares similar levels of accuracy to IOTA LR2 and SR for basic discrimination between cancer and benign disease. Its use has the potential to further improve and fine-tune management decisions and so reduce the morbidity and mortality associated with adnexal pathology. Biomarkers are also attractive, popular and recommended tools to support clinical judgment of the nature of an adnexal mass. At present two novel commercial biomarkerbased algorithms have been developed in order to improve the poor accuracy of serum CA125; the Multivariate Index Assay and the ROMA algorithm. The latter utilises levels of CA125 and a new emerging epithelial biomarker human-epididymis-protein-4 (HE4) combined with the patient’s menopausal status to classify patients as at high or low risk for malignancy (Chapter 7). This test rapidly gained widespread attention, as evidenced by its numerous validation studies throughout the world. However, based on the findings of this thesis both commercial tests still seem redundant for preoperative diagnosis if good quality transvaginal ultrasonography (TVS) is available and the IOTA models are used in the correct manner (Chapter 3 and Chapter 7). TVS is accepted as the most appropriate initial imaging investigation to identify and characterise any mass if present in women suspected of having adnexal pathology (chapter 8). Other imaging modalities such as computed-tomography (CT) and [18F]-fluorodeoxyglucose positron emission tomography ([18F]-FDG-PET) both lack accuracy for preoperative diagnosis and are more useful tools for staging of malignant disease and the assessment of ovarian cancer recurrence. Magnetic resonance imaging (MRI) may have a limited role to play in characterising so-called “difficult masses” after ultrasound review. The IOTA prediction models and rules offer new criteria that we can use to clearly define complex or “difficult to classify” adnexal masses to focus the role for second-line imaging tests such as conventional MRI combined with dynamic contrastenhanced (DCE) or diffusion-weighted (DWI) sequences on masses where further tests other than ultrasonography would be of value to minimise healthcare costs (Chapter 8). The IOTA study has made significant progress in relation to the preoperative classification of adnexal masses, however what is now needed is to see if these or new diagnostic tools will have a positive influence on both clinical management and patient outcomes in true interventional studies; can assist clinicians to select patients with adnexal masses that are suitable for expectant management; and that will work in all health care settings (i.e. primary vs secondary vs tertiary care). The future agenda of the IOTA project will focus on these important themes (Chapter 9).