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Niraula S.,University of Toronto | Chi K.,The Prostate Center | Joshua A.M.,University of Toronto
Hormones and Cancer | Year: 2012

It is now almost 70 years since Charles Huggins described the relationship between testosterone and the prostate gland. Arguably defining one of the first targeted therapies, the reduction of testosterone to castrate levels remains unaltered as the standard of care for men with metastatic prostate cancer. The failure of castration to permanently control the growth of prostate cancer leads to a state called castration-resistant prostate cancer (CRPC). Whilst numerous mechanisms have been suggested for the emergence of castration resistance [Scher and Sawyers (J Clin Oncol 23(32):8253-8261, 2005); Chen et al. (Curr Opin Pharmacol 8(4):440-448, 2008), Pienta and Bradley (Clin Cancer Res 12(6):1665-1671, 2006); Feldman and Feldman (Nat Rev Cancer 1(1):34-45, 2001); Mostaghel and Nelson (Best Pract Res Clin Endocrinol Metab 22(2):243-258, 2008)], a greater understanding of prostate cancer biology suggests that many such cancers retain a dependency on androgens and endeavour to increase bioavailable androgens through mechanisms such as AR amplification and intracrine androgen synthesis [Mohler et al. (Clin Cancer Res 10(2):440-448, 2004); Attard et al. (Clin Cancer Res 17(7):1649-1657, 2011); Hu et al. (Expert Rev Endocrinol Metab 5(5):753-764, 2010)]. With the recent approval of abiraterone acetate (Zytiga) and the pending approval of MDV3100, this article previews the future directions in clinical development and issues that will arise with the next generation of androgen-targeted agents. © 2011 Springer Science+Business Media, LLC.

Kuramae H.,Tokyo University of Information Sciences | Hirata Y.,Tokyo University of Information Sciences | Hirata Y.,University of Tokyo | Bruchovsky N.,The Prostate Center | And 5 more authors.
Chaos | Year: 2011

A new parameter estimation method for nonlinear systems from time series data is proposed. For the purpose of unbiased estimation, we employ the idea of bootstrap method on regression problems. Our method can be applied into even short and noisy data and is expected to give us a robust estimation. Some benchmarks of estimating chaotic models show its practical applicability. We also try to apply this method to analysis for intermittent hormonal therapy for prostate cancer by using a mathematical model and real clinical data. © 2011 American Institute of Physics.

Mostafid H.,Royal Surrey County Hospital | Kirby R.,The Prostate Center | Fitzpatrick J.M.,Irish Cancer Society | Bryan R.T.,University of Birmingham
Urology Practice | Year: 2014

Introduction: Stage Ta bladder cancer accounts for around half of all new cases of urothelial bladder cancer. It shows heterogeneous behavior with a 5-year recurrence rate of 31% to 78% and a progression rate of 0.8% to 45%. Optimal management is crucial to achieve safe and yet economical long-term outcomes. We provide an overview of such management. Methods: Using AUA, NCCN®, EAU and ICUD-EAU guidelines as the basis of this nonsystematic review we performed PubMed® searches to update the literature in this field and expand on topics of particular interest or controversy. Results: This study provides an overview for the practicing urologist of safe, economical care of stage Ta bladder cancer with regard to risk stratification, preoperative and perioperative care, subsequent adjuvant treatment, surveillance, recurrence management and long-term outcomes. While these recommendations are already incorporated in current guidelines, some aspects deserve further discussion or have been the subject of relevant research subsequent to guideline publication. Conclusions: The traditional view that stage Ta bladder cancer is invariably synonymous with low risk disease requires reevaluation. Modern management of stage Ta bladder cancer depends on initial risk stratification that allows for subsequent management based on a number of evidence-based guidelines. Given the usual long clinical course of stage Ta bladder cancer, such an approach ensures not only safe but also economical care of this group of patients. © 2014 American Urological Association Education and Research, Inc.

Santa Mina D.,University of Guelph | Santa Mina D.,The Prostate Center | Guglietti C.L.,York University | Alibhai S.M.H.,University of Toronto | And 9 more authors.
Journal of Cancer Survivorship | Year: 2014

Purpose: Recent literature has shown that preoperative physical activity (PA) can positively influence surgical outcomes. It is unknown whether the effect of meeting PA guidelines for cancer survivors can impact quality of life following radical prostatectomy for prostate cancer. Methods: We reviewed our institutional database of prostate cancer outcomes and included patients that underwent radical prostatectomy and completed the Godin-Shephard Leisure Time Exercise Questionnaire (GLTEQ), the Patient-Oriented Prostate Utility Scale (PORPUS), the International Prostate Symptom Score (IPSS), and the five-item International Index of Erectile Function (IIEF). Participants were categorized as meeting or not meeting the American College of Sports Medicine physical activity guidelines for cancer survivors (150 min of moderate intensity or 75 min of vigorous intensity PA per week). Radical prostatectomy outcomes were measured preoperatively and at 6 and 26-weeks postoperatively. Results: From June 2008 to August 2012, 509 men underwent curative, nerve-sparing radical prostatectomy for prostate cancer and completed the GLTEQ, of whom 46 % met the PA guidelines. Prior to surgery, men that met the PA guidelines reported higher quality of life (p < 0.001) and erectile function (p = 0.049) than men that did not meet the guidelines. Quality of life at all postoperative timepoints was higher for men that met the PA guidelines after adjusting for age, preoperative body mass index, and surgical approach (p = 0.02). Men that met the PA guidelines were 19 % less likely to be incontinent at 6 weeks postoperatively (p = 0.028). Conclusion: PA volume may be a useful marker at predicting postoperative recovery of quality of life and urinary incontinence following radical prostatectomy. Implications for Cancer Survivors: Cancer survivors should be encouraged to meet PA guidelines prior to surgery in an effort to attenuate the decline in HRQOL and facilitate recovery. © 2013 Springer Science+Business Media New York.

Billia M.,Guys and St Thomas Hospitals NHS Foundation Trust | Billia M.,Kings College London | Elhage O.,Guys and St Thomas Hospitals NHS Foundation Trust | Elhage O.,Kings College London | And 10 more authors.
World Journal of Urology | Year: 2014

Introduction: In the last 10 years, robotic-assisted radical prostatectomy (RARP) has become increasingly popular as witnessed by an increased number of publications. However, there is still little known about the long-term oncologic outcomes of this technique. The aim of this study is to assess the oncologic outcomes of patients who underwent RARP at least 5 years ago, with an emphasis on biochemical recurrence-free survival (BCRFS). Materials and methods: In 2004, RARP was introduced at our institutions. Records of all patients having RARP were prospectively collected in a dedicated database as part of the NUVOLA-BAUS project. For the present study, we selected only patients who had a follow-up of at least 5 years. Endpoints were BCRFS rate and 5-year cancer-specific survival (CSS). Results: Overall, we identified 175 patients; 61.7 % of patients had Gleason 7-9 disease and 26.9 % had pT ≥ 3 disease at final pathology. Eight patients (4.5 %) had biochemical recurrence at follow-up. Overall 5-year BCRFS rate was 95.4 %, while it was 97.6, 91 and 50 % in pT2, pT3 and pT4 diseases, respectively. Among the patients who recurred, the mean time to recurrence was 22.1 ± 8.8 months. These patients received salvage external beam radiation treatment combined with hormonal therapy (anti-androgen + LHRH analogue) or hormonal therapy alone. 5-year CSS was 98.3 % (172/175): in 2 cases, the specimen showed pT4 cancer, while lymph node metastasis was noted in one case. Conclusion: The 5-year BCRFS and CSS after RARP are encouraging even in a population with significant high-risk disease © 2013 Springer-Verlag Berlin Heidelberg.

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