Medicine (Austin & Northern Health) - Theses

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End date: 2018 × Start date: 2010 × Type: Masters Research thesis × Subject: active surveillance, prostate cancer, nomogram, patient selection ×

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    Selection of men for active surveillance in low risk prostate cancer
    Wong, Lih-Ming ( 2013)
    Aims: Active surveillance (AS) is a management strategy that aims to avoid over-treatment of indolent prostate cancer, monitor for development of more aggressive disease, and intervene within the window of curability. Interest in AS has increased as large randomized screening trials suggest many men with prostate cancer are over-diagnosed and over-treated. Suitability of men for AS is determined by criteria that were found to predict "insignificant tumours", defined as tumours of volume <0.5ml. However, amongst the published literature on AS, variations in eligibility criteria exist between individual institutions. The primary aim of this thesis was to examine the ability of certain published AS eligibility criteria to include only men with insignificant tumours, and avoid selection of men with more aggressive disease. Methods: To investigate eligibility criteria for AS, data on men who were suitable for AS but underwent upfront radical prostatectomy was analysed. Initially, a database from Addenbrookes Hospital, Cambridge, United Kingdom was utilized. Subsequently, a collaboration of radical prostatectomy data between Addenbrookes Hospital, United Kingdom; Vancouver Prostate Centre, Canada; and Royal Melbourne Hospital, Australia was formed. First, the Cambridge database was used to assess a National Institute for Health and Clinical Excellence (NICE) guideline. Here, it had previously been stated “men with low-risk localised prostate cancer who are considered suitable for radical treatment should first be offered active surveillance”. Subsequently, the combined database was utilized to examine two of the commonly used AS criteria (Sunnybrook Toronto and European Prostate Cancer Research International: Active Surveillance (PRIAS)). Here, the number of men suitable for AS according to each criteria, and proportions of men with upgrading and upstaging at radical prostatectomy were described. Multivariate logistical regression was done to identify predictors of more aggressive, or high-risk, disease, and analysis to create a predictive model for both indolent and high-risk disease performed. Results: When reviewing the NICE guideline, their definition of low risk prostate cancer, was applied to the Cambridge radical prostatectomy database (n=700) and 39.2% of men (n=275) deemed suitable. In this group of NICE low risk patients, 30.6% (n=84/275) of men had features of more aggressive disease (Gleason sum ≥7, pathological stage ≥ pT3) at upfront radical prostatectomy. In selecting men for AS, application of more stringent criteria was found to effectively halve the number of men suitable for AS (Sunnybrook criteria n=800, compared to PRIAS criteria n=410). The proportion of men with increase in Gleason grade (≥7) was 42.7-50.6%, and increase in stage was 12.4-17.6%. Predictors of high-risk disease included increasing age, cT2, increasing PSA and number of positive cores. More men in Cambridge, compared to Vancouver and Melbourne, were found to have pT3 disease (26% versus 12%). To assist selection of men in the UK for AS, from the Cambridge data, we generated a nomogram predicting high-risk features in patients who meet the Sunnybrook Toronto criteria (AUC of 0.72). Conclusions: In selecting men for AS, a proportion of them will harbour undiagnosed high-risk disease. Using more stringent criteria may reduce this number but at the cost of including fewer men who may benefit from AS. Predictive models may assist with selection of men but the future likely lies in better tests, be it imaging or biomarkers, to be performed at time of selection and during the course of AS.