Open Access

INTRODUCTION

Leonard G. Gomella¹, Daniel P. Petrylak², Bobby Shayegan³
Canadian Journal of Urology, Vol.21, Suppl.2, pp. 1-6, 2014
Abstract instruction: Introduction: Newer approaches to the management of advanced prostate cancer have rapidly evolved. While basic androgen deprivation remains as the first line in newly diagnosed hormone naïve metastatic prostate cancer, the agents used and strategies followed have undergone significant changes. Numerous new agents such as sipuleucel-T, abiraterone, enzalutamide, cabazitaxel and radium-223 have all been approved since 2010 to treat metastatic castration-resistant prostate cancer (CRPC). New imaging techniques to detect advanced disease such as F-18 PET, 11C-choline PET and other modalities are becoming available. The concepts of "bone health" and the management of side effects related… More >

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Derya Tilki^1,2, Christopher P. Evans¹
Canadian Journal of Urology, Vol.21, Suppl.2, pp. 7-13, 2014
Abstract instruction: Introduction: One fifth of men with newly diagnosed prostate cancer present with locally advanced or metastatic disease. Androgen deprivation therapy (ADT) is the standard systemic therapy in these patients. Despite initial response, essentially all patients will develop castration-resistant prostate cancer (CRPC). In this review, we will discuss the revised definitions of CRPC and the latest understanding of the biology of the androgen/androgen receptor axis in the development of advanced prostate cancer.
instruction: Materials and methods: A systematic literature review was conducted via electronic database articles based on title, abstract, study format, and content. The majority of… More >

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Kyle O. Rove, E. David Crawford
Canadian Journal of Urology, Vol.21, Suppl.2, pp. 14-21, 2014
Abstract instruction: Introduction: Androgen deprivation therapy (ADT) is a mature therapy for the treatment of advanced prostate cancer, and yet despite many years of use, there is still much about its use, side effects, efficacy, and outcomes for which the urology community does not have answers.
instruction: Materials and methods: A literature search was performed to review ADT use in the modern era, specifically examining adjuvant ADT after primary therapy, continuous versus intermittent ADT, disadvantages of luteinizing hormone-releasing hormone (LHRH) agonists versus newer LHRH antagonists, and controversies of combined androgen blockade.
instruction: Results: ADT has little role as primary… More >

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Judd W. Moul
Canadian Journal of Urology, Vol.21, Suppl.2, pp. 22-27, 2014
Abstract instruction: Introduction: Androgen deprivation therapy (ADT) is the lynchpin of treatment for advanced prostate cancer. Prescribing physicians and patients have a choice between orchiectomy, luteinizing hormone-releasing hormone (LHRH) agonists, combined androgen deprivation (CAD) or LHRH antagonists.
instruction: Materials and methods: Literature relating to the use of LHRH antagonists in the management of prostate cancer was reviewed.
instruction: Results: Abarelix was the first-in-class LHRH pure antagonist that was Food and Drug Administration (FDA) approved in 2003. Due to a variety of concerns including hypersensitivity reactions it was withdrawn from the United States (U.S.) market in 2005. The only currently… More >

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Shawn Dason, Christopher Brian Allard, Jing Gennie Wang, Jen Hoogenes, Bobby Shayegan
Canadian Journal of Urology, Vol.21, Suppl.2, pp. 28-36, 2014
Abstract instruction: Introduction: Intermittent androgen deprivation therapy (IADT) for prostate cancer involves cycles of androgen deprivation therapy (ADT) with a period between cycles where testosterone is allowed to rise above castrate levels. A number of recent randomized controlled trials (RCTs) have compared survival and health-related quality-of-life (HRQOL) between IADT and continuous ADT (CADT). This review seeks to critically analyze these published trials for their relevance to clinical practice.
instruction: Materials and methods: Published trials were retrieved from a systematic search of MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials databases using relevant keywords. Recent systematic reviews… More >

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Sohaib Al-Asaaed, Eric Winquist
Canadian Journal of Urology, Vol.21, Suppl.2, pp. 37-41, 2014
Abstract instruction: Introduction: Castration-resistant prostate cancer (CRPC) is the single common pathway to prostate cancer death. For men with symptomatic metastatic disease, docetaxel chemotherapy remains a standard of care. However, blood prostate-specific antigen (PSA) testing allows the identification of CRPC before clinical metastases or symptoms occur, providing a long diagnostic lead time in many patients. The use of secondary hormonal manipulations (SHMs) in men not candidates for immediate chemotherapy is reviewed.
instruction: Materials and methods: PubMed was searched for randomized clinical trials, systematic reviews or clinical practice guidelines addressing SHMs in CRPC.
instruction: Results: A recent systematic review and… More >

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David Leung, Saravanan Krishnamoorthy, Lawrence Schwartz, Chaitanya Divgi
Canadian Journal of Urology, Vol.21, Suppl.2, pp. 42-47, 2014
Abstract instruction: Introduction: In conjunction with biomarkers, imaging is an important component of the diagnostic workup and subsequent management of men with prostate cancer.
instruction: Materials and methods: The relevant literature was retrieved from a search of MEDLINE with appropriate keywords.
instruction: Results: Osseous metastases develop in close to 90% of patients with metastatic prostate cancer, thus making bone scans (single photon, using Tc-99m labeled phosphonates) the mainstay of imaging in advanced prostate cancer. Bone scans are limited by their lack of specificity and an unclear relationship between bone scan changes and disease progression or response to therapy. In… More >

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Leonard G. Gomella, Francisco Gelpi-Hammerschmidt, Chandan Kundavram
Canadian Journal of Urology, Vol.21, Suppl.2, pp. 48-56, 2014
Abstract instruction: Introduction: New treatment options for metastatic castration-resistant prostate cancer (mCRPC) have become available over the last few years should primary treatments and androgen deprivation therapies fail. While historically not considered to be amenable to immunotherapy, the treatment of advanced prostate cancer using this approach is an area of intense interest and now clinical application.
instruction: Materials and methods: Recent literature on castration-resistant prostate cancer management with a focus on immunotherapeutic strategies was reviewed. Mechanisms of action involving the immunologic treatment of cancer were identified. Agents in clinical trials with near-term application in prostate cancer were also… More >

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Elahe A. Mostaghel^1,2, Daniel W. Lin³
Canadian Journal of Urology, Vol.21, Suppl.2, pp. 57-63, 2014
Abstract instruction: Introduction: While androgen deprivation therapy remains the primary treatment modality for patients with metastatic prostate cancer, treatment is uniformly marked by progression to castration-resistant prostate cancer (CRPC). Abiraterone is the first new drug to enter clinical practice in a series of novel agents designed to potently target adrenal and tumor androgen production.
instruction: Materials and methods: Herein, we review the mechanism of action of abiraterone and the phase III data supporting its approval for patients with metastatic CRPC. We discuss practical treatment considerations, including the incidence and management of side effects and monitoring requirements, and conclude More >

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Jean Hoffman-Censits, Wm. Kevin Kelly
Canadian Journal of Urology, Vol.21, Suppl.2, pp. 64-69, 2014
Abstract instruction: Introduction: We summarize the development, definitive trials, and practical use of enzalutamide for practicing urologists and medical oncologists. The care paradigm for patients with metastatic castration-resistant prostate cancer (mCRPC) is a changing landscape, with the ongoing discovery of drivers of cancer progression yielding actionable targets for drug development. Since 2010, sipuleucel-T, cabazitaxel, abiraterone with prednisone, radium-223 and enzalutamide have been Food and Drug Administration (FDA) approved based upon improvement in overall survival in men with mCRPC.
instruction: Materials and methods: A MEDLINE search for "enzalutamide or MDV3100" yielded 258 results. Prospective trials were reviewed. Abstracts from… More >

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Robert B. Den^1,2,3, Laura A. Doyle², Karen E. Knudsen^1,2,3,4
Canadian Journal of Urology, Vol.21, Suppl.2, pp. 70-76, 2014
Abstract instruction: Introduction: Bone-seeking radiopharmaceuticals have been used for decades in the palliation of pain from bone metastases emerging from prostate cancer. Recent clinical evidence has demonstrated an improved survival in men with metastatic castration-resistant prostate cancer (CRPC) with radium-223.
instruction: Materials and methods: A review of the literature was performed to identify the role of radiopharmaceuticals in the management of prostate cancer. We focused on prospective trials in order to identify the highest level of evidence describing this therapy. Further, we focused on providing a clinical guide for the use of radium-223.
instruction: Results: The phase III ALSYMPCA… More >

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Daniel P. Petrylak
Canadian Journal of Urology, Vol.21, Suppl.2, pp. 77-83, 2014
Abstract instruction: Introduction: Chemotherapy, once thought to be toxic and ineffective in men with castration-resistant prostate cancer (CRPC), has a significant impact on survival and quality-of-life in these patients. This article summarizes recent studies performed with two Food and Drug Administration (FDA) approved agents which have improved survival in men with CRPC, docetaxel and cabazitaxel.
instruction: Materials and methods: The literature on cytotoxic chemotherapy for castration-resistant prostate cancer was reviewed. The individual efficacy, mechanisms of chemotherapeutic action, and appropriate disease states of administration were identified. Recent clinical trial results of chemotherapy combined with targeted agents was also reviewed.
instruction:… More >

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Valentina Butoescu, Bertrand Tombal
Canadian Journal of Urology, Vol.21, Suppl.2, pp. 84-92, 2014
Abstract instruction: Introduction: In the advanced stage of prostate cancer, bone is consistently the first and, later on, the dominant extra-nodal metastatic site. Bone metastases account for most of prostate cancer's morbidity.
instruction: Materials and methods: We have performed a literature review using the MEDLINE database for publications on: 1) bone metastases (androgen deprivation therapy); 2) cancer treatment-induced bone loss; 3) skeletal-related events; 4) denosumab; 5) zoledronic acid.
instruction: Results: Prostate cancer cells disrupt the normal bone remodeling process, invade the skeletal environment, and ultimately weaken the bone structure. This may result in skeletal complications, also known as skeletal-related… More >

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Robert Dreicer
Canadian Journal of Urology, Vol.21, Suppl.2, pp. 93-97, 2014
Abstract instruction: Introduction: Rapid progress has recently been made in understanding the biology of advanced prostate cancer. This has translated into the development of a number of novel agents to treat metastatic castration-resistant prostate cancer (mCRPC).
instruction: Materials and methods: The relevant literature was retrieved from a search of MEDLINE with appropriate keywords.
instruction: Results: Therapeutic approaches to mCRPC include chemotherapy, hormonal manipulation, immunotherapy and radioisotope therapy. Docetaxel and cabazitaxel are cytotoxic agents which have demonstrated a modest impact on survival. Hormonal manipulation with abiraterone and enzalutamide have also been reported to be beneficial in mCRPC. The radioisotope radium-223 More >

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Gregory R. Thoreson, Bishoy A. Gayed, Paul H. Chung, Ganesh V. Raj
Canadian Journal of Urology, Vol.21, Suppl.2, pp. 98-105, 2014
Abstract instruction: Introduction: Prostate cancer continues to be the second leading cause of cancer-related mortality in men within the United States. Despite a consistent decline in prostate cancer mortality over the past two decades, the prognosis for men with metastatic prostate cancer remains poor with no curative therapies. In this article, we review the recently approved and emerging therapeutics for patients with castration-resistant prostate cancer.
instruction: Materials and methods: An advanced search was conducted on the ClinicalTrials.gov database, using search terms "metastatic prostate cancer", and limiting results to phase II-IV clinical trials. Clinically relevant emerging therapeutics were selected… More >

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