The ProtecT trial: analysis of the patient cohort, baseline risk stratification and disease progression.

OBJECTIVE: To test the hypothesis that the baseline clinico-pathological features of the men with localized prostate cancer (PCa) included in the ProtecT (Prostate Testing for Cancer and Treatment) trial who progressed (n = 198) at a 10-year median follow-up were different from those of men with stable disease (n = 1409). PATIENTS AND METHODS: We stratified the study participants at baseline according to risk of progression using clinical disease stage, pathological grade and PSA level, using Cox proportional hazard models. RESULTS: The findings showed that 34% of participants (n = 505) had intermediate- or high-risk PCa, and 66% (n = 973) had low-risk PCa. Of 198 participants who progressed, 101 (51%) had baseline International Society of Urological Pathology Grade Group 1, 59 (30%) Grade Group 2, and 38 (19%) Grade Group 3 PCa, compared with 79%, 17% and 5%, respectively, for 1409 participants without progression (P < 0.001). In participants with progression, 38% and 62% had baseline low- and intermediate-/high-risk disease, compared with 69% and 31% of participants with stable disease (P < 0.001). Treatment received, age (65-69 vs 50-64 years), PSA level, Grade Group, clinical stage, risk group, number of positive cores, tumour length and perineural invasion were associated with time to progression (P ≤ 0.005). Men progressing after surgery (n = 19) were more likely to have a higher Grade Group and pathological stage at surgery, larger tumours, lymph node involvement and positive margins. CONCLUSIONS: We demonstrate that one-third of the ProtecT cohort consists of people with intermediate-/high-risk disease, and the outcomes data at an average of 10 years' follow-up are generalizable beyond men with low-risk PCa

Ablative therapy for people with localised prostate cancer : a systematic review and economic evaluation

The research reported in this issue of the journal was funded by the HTA programme as project number 10/136/01. The contractual start date was in April 2012. The draft report began editorial review in October 2013 and was accepted for publication in April 2014. The authors have been wholly responsible for all data collection, analysis and interpretation, and for writing up their work. The HTA editors and publisher have tried to ensure the accuracy of the authors’ report and would like to thank the reviewers for their constructive comments on the draft document. However, they do not accept liability for damages or losses arising from material published in this report. Acknowledgements We thank l the people recruited from the local UCAN for providing valuable consumer insight and advice through their participation as members of the project focus group: - Mark Emberton (Professor of Interventional Oncology), Damian Greene (consultant urologist), Axel Heidenreich (Professor and Director of Department of Urology), Christoph von Klot (specialist in brachytherapy), Roger Kockelbergh (BAUS chairman and Clinical Director of Urology) and Axel Merserburger (Deputy Clinical Director of Urology and Urologic Oncology) for providing their clinical expertise as members of the project advisory group - Edgar Paez (consultant urologist) and Gill Lawrence (Head of Radiotherapy Physics) for providing a list of staff time by grade and specialty involved in EBRT - Debbie Bennett (Radiotherapy Service Manager) for providing estimates for the expected number of uses for EBRT - Ian Pedley (clinical director/clinical oncologist) and Gill Lawrence for providing a list of all resource inputs relevant to brachytherapy - Steve Locks (Consultant Clinical Scientist in Radiotherapy) for providing a list of reusable equipment and consumables used during brachytherapy, along with their unit costs - Sue Asterling (urology research nurse) and Mark Kelly (Acting Divisional General Manager – Theatres) for providing a list of all resource inputs relevant to cryotherapy - Lara Kemp for providing secretarial support. The Health Services Research Unit is core funded by the Chief Scientist Office of the Scottish Government Health Directorates.Peer reviewedPublisher PD

Prostasomas: search of biomarkers for the early detection of prostate cancer

El cáncer de próstata es la segunda enfermedad más diagnosticada en hombres a nivel mundial, con una tasa de mortalidad creciente en los últimos años. Actualmente, se cuenta con dos pruebas de detección temprana: la medición de los niveles en sangre del antígeno prostático específico y el tacto rectal de la próstata. Sin embargo, estas pruebas no presentan óptima especificidad y sensibilidad para su detección. Aunque diferentes estudios han buscado nuevos biomarcadores mediante la implementación de tecnologías, como secuenciación de nueva generación, espectrometría de masas, entre otras, aún persisten las mismas desventajas, por lo que no les ha permitido a estos su uso en la práctica clínica; razón por la cual, el descubrimiento de nuevos biomarcadores para el diagnóstico de cáncer de próstata, constituye un desafío para la comunidad científica. Los prostasomas corresponden a vesículas extracelulares secretadas por el tejido prostático normal o tumoral que pueden ser detectadas en diferentes fluidos. Estructuralmente, los prostasomas difieren de otros exosomas, por su tamaño, composición de membrana y contenido específico de proteínas, lo que los convierten en una fuente potencial y novedosa de biomarcadores clínicos.  En este contexto, esta revisión presenta un panorama general de los biomarcadores proteicos, aislados desde prostasomas presentes en diferentes fluidos biológicos, para el posible diagnóstico de cáncer de próstata. Para ello se realizó una búsqueda sistemática en PubMed para estudios en proteómica para cáncer de próstata, con criterios como: vesículas extracelulares, exosomas y prostasomas, asimismo, sangre, orina, líquido seminal, entre otras muestras biológicas.Prostate cancer is the second most diagnosed disease in men worldwide, with an increasing mortality rate in recent years. Currently, there are two early detection tests, the measurement of blood levels of prostate-specific antigen and digital rectal examination of the prostate. However, these tests do not present optimal specificity and sensitivity for their detection. Although different studies have looked for new biomarkers by means of the implementation of technologies, such as new generation sequencing, mass spectrometry, among others, the same disadvantages persist, therefore, they have not allowed their use in clinical practice; The discovery of new biomarkers for the diagnosis of prostate cancer is a challenge for the scientific community. Prostasomes correspond to extracellular vesicles secreted by normal prostate or tumor tissue that can be detected in different fluids. Structurally, prostasomes differ from other exosomes, by their size, membrane composition and specific protein content, which makes them a potential and novel source of clinical biomarkers. In this context, this review presents an overview of protein biomarkers, isolated from prostasomes present in different biological fluids, for the possible diagnosis of prostate cancer. For this, a systematic PubMed search was carried out for studies in proteomics for prostate cancer, with criteria such as extracellular vesicles, exosomes and prostasomes, as well as blood, urine, seminal fluid, among other biological samples

Active Surveillance for Prostate Cancer: A Systematic Review of the Literature

Context: Prostate cancer (PCa) remains an increasingly common malignancy worldwide. The optimal management of clinically localized, early-stage disease remains unknown, and profound quality of life issues surround PCa interventions. Objective: To systematically summarize the current literature on the management of low-risk PCa with active surveillance (AS), with a focus on patient selection, outcomes, and future research needs. Evidence acquisition: A comprehensive search of the PubMed and Embase databases from 1980 to 2011 was performed to identify studies pertaining to AS for PCa. The search terms used included prostate cancer and active surveillance or conservative management or watchful waiting or expectant management. Selected studies for outcomes analysis had to provide a comprehensive description of entry characteristics, criteria for surveillance, and indicators for further intervention. Evidence synthesis: Data from seven large AS series were reviewed. Inclusion criteria for surveillance vary among studies, and eligibility therefore varies considerably (4-82%). PCa-specific mortality remains low (0-1%), with the longest published-median follow-up being 6.8 yr. Up to one-third of patients receive secondary therapy after a median of about 2.5 yr of surveillance. Surveillance protocols and triggers for intervention vary among institutions. Most patients are treated for histologic reclassification (27-100%) or prostate-specific antigen doubling time <3 yr (13-48%), while 7-13% are treated with no evidence of progression. Repeat prostate biopsy with a minimum of 12 cores appears to be important for monitoring patients for changes in tumor histology over time. Conclusions: AS for PCa offers an opportunity to limit intervention to patients who will likely benefit the most from radical treatment. This approach confers a low risk of disease-specific mortality in the short to intermediate term. An early, confirmatory biopsy is essential for limiting the risk of underestimating tumor grade and amount. (C) 2012 European Association of Urology. Published by Elsevier B. V. All rights reserved

MRI in active surveillance: a critical review

INTRODUCTION: Recent technological advancements and the introduction of modern anatomical and functional sequences have led to a growing role for multiparametric magnetic resonance imaging (mpMRI) in the detection, risk assessment and monitoring of early prostate cancer. This includes men who have been diagnosed with lower-risk prostate cancer and are looking at the option of active surveillance (AS). The purpose of this paper is to review the recent evidence supporting the use of mpMRI at different time points in AS, as well as to discuss some of its potential pitfalls. METHODS: A combination of electronic and manual searching methods were used to identify recent, important papers investigating the role of mpMRI in AS. RESULTS: The high negative predictive value of mpMRI can be exploited for the selection of AS candidates. In addition, mpMRI can be efficiently used to detect higher risk disease in patients already on surveillance. CONCLUSION: Although there is an ongoing debate regarding the precise nature of its optimal implementation, mpMRI is a promising risk stratification tool and should be considered for men on AS