Menon, U.; (2007) Ovarian cancer screening in the general population. Doctoral thesis , University of London.

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Abstract

Despite significant improvements in therapy, ovarian cancer continues to be a leading cause of death amongst women with gynaecological malignancies. Advanced stage at diagnosis is thought to be a major contributor to mortality. Hence, there is considerable interest in early detection through screening. In the 1990s, Professor Jacobs pioneered the development of a multimodal ovarian cancer screening (OCS) strategy using serum CA125 as the first line screen and pelvic ultrasound as the second line test. This thesis summarises the next steps in the journey with refining of the screening algorithm, feasibility testing in a pilot randomised control trial (RCT) and finally setting up and recruiting 200,000 women into the largest ever RCT . The risk of ovarian cancer in postmenopausal women with elevated CA125 levels was established through a detailed analysis of 1219 pelvic scans from 741 women with raised CA125 levels in the completed trial of 22,000 women. Based on this, the multimodal 'Risk of Ovarian Cancer' (ROC) algorithm was refined and morphology instead of volume was used to interpret the ovarian scans. The refined ROC algorithm was then prospectively evaluated in a pilot RCT of 13,582 postmenopausal women. The trial established that screening using the ROC algorithm was feasible and could achieve high specificity and positive predictive value. The improved performance characteristics of the screening strategy and the experience accumulated in running and organising the pilot trial led to the design and successful implementation of a RCT - the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) - to assess the impact of early detection on disease mortality. The trial commenced in 2001 with recruitment of 202,638 postmenopausal women by September 2005. The issues involved in setting up the trial, recruitment of 202,000 women and the baseline characteristics of this population are described.

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