Surgery (RMH) - Research Publications

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Author: Costello, Anthony × End date: 2012 × Start date: 2012 × Type: Journal Article ×

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    International multicentre study examining selection criteria for active surveillance in men undergoing radical prostatectomy
    Wong, L-M ; Neal, DE ; Johnston, RB ; Shah, N ; Sharma, N ; Warren, AY ; Hovens, CM ; Goldenberg, SL ; Gleave, ME ; Costello, AJ ; Corcoran, NM (NATURE PUBLISHING GROUP, 2012-10-23)
    BACKGROUND: The controversies concerning possible overtreatment of prostate cancer, highlighted by debate over PSA screening, have highlighted active surveillance (AS) as an alternative management option for appropriate men. Regional differences in the underlying prevalence of PSA testing may alter the pre-test probability for high-risk disease, which can potentially interfere with the performance of selection criteria for AS. In a multicentre study from three different countries, we examine men who were initially suitable for AS according to the Toronto and Prostate Cancer Research International: Active Surveillance (PRIAS) criteria, that underwent radical prostatectomy (RP) in regards to:1.the proportion of pathological reclassification(Gleason score ≥7, ≥pT3 disease),2.predictors of high-risk disease,3.create a predictive model to assist with selection of men suitable for AS. METHODS: From three centres in the United Kingdom, Canada and Australia, data on men who underwent RP were retrospectively reviewed (n=2329). Multivariable logistic regression was performed to identify predictors of high-risk disease. A nomogram was generated by logistic regression analysis, and performance characterised by receiver operating characteristic curves. RESULTS: For men suitable for AS according to the Toronto (n=800) and PRIAS (410) criteria, the rates for upgrading were 50.6, 42.7%, and upstaging 17.6, 12.4%, respectively. Significant predictors of high-risk disease were:•Toronto criteria: increasing age, cT2 disease, centre of diagnosis and number of positive cores.•PRIAS criteria: increasing PSA and cT2 disease.Cambridge had a high pT3a rate (26 vs 12%). To assist selection of men in the United Kingdom for AS, from the Cambridge data, we generated a nomogram predicting high-risk features in patients who meet the Toronto criteria (AUC of 0.72). CONCLUSION: The proportion of pathological reclassification in our cohort was higher than previously reported. Care must be used when applying the AS criteria generated from one population to another. With more stringent selection criteria, there is less reclassification but also fewer men who may benefit from AS.
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    Levels of a subpopulation of platelets, but not circulating endothelial cells, predict early treatment failure in prostate cancer patients after prostatectomy
    Wong, CKE ; Namdarian, B ; Chua, J ; Chin, X ; Speirs, R ; Nguyen, T ; Fankhauser, M ; Pedersen, J ; Costello, AJ ; Corcoran, NM ; Hovens, CM (NATURE PUBLISHING GROUP, 2012-10-23)
    BACKGROUND: Angiogenesis is one of the hallmarks of cancer driving tumour growth and ultimately metastasis. Circulating endothelial cells (CECs) and circulating endothelial progenitor (CEPs) cells have been reported as candidate surrogate markers for tumour vascularisation. Our aim was to investigate the potential use of these circulating cells levels as predictors of prostate cancer treatment failure and metastasis. METHODS: We examined the levels of CD31(+)CD45(-) cells (CECs) and CD31(+)CD45(-)CD117(+) (CEPs) in s.c. and orthotopic models of human prostate cancers and correlated measurements with tumour size, volume and microvessel density (MVD). We then performed a prospective cohort study in 164 men with localised prostate cancer undergoing prostatectomy. The CD31(+)CD45(-), CD31(+)CD45(-)CD146(+) (CECs) and CD31(+)CD45(intermediate)CD133(+) (CEPs) populations were quantified and subsequently enriched for further characterisation. RESULTS: In preclinical models, levels of CD31(+)CD45(-) cells, but not CEPs, were significantly elevated in tumour-bearing mice and correlated with tumour size, volume and MVD. In our human prospective cohort study, the levels of CD31(+)CD45(-) cells were significantly higher in men who experienced treatment failure within the first year, and on logistic regression analysis were an independent predictor of treatment failure, whereas neither levels of CECs or CEPs had any prognostic utility. Characterisation of the isolated CD31(+)CD45(-) cell population revealed an essentially homogenous population of large, immature platelets representing <0.1% of circulating platelets. CONCLUSION: Elevated levels of a distinct subpopulation of circulating platelets were an independent predictor for early biochemical recurrence in prostate cancer patients within the first year from prostatectomy.