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Genitourinary Cancer Prostate Cancer Combination of Hormone Therapy and Radiotherapy in Treatment of Locally Advanced Prostate Cancer—Recent Developments and Update Roger YC Huang, MBChB, FRANZCR, 1 Charles N Catton, MD, FRCPC 2 and Padraig R Warde, MB, MRCPI, FRCPC 3 1. Radiation Oncology Fellow, Department of Radiation Oncology, Princess Margaret Hospital/University Health Network; 2. Professor, Department of Radiation Oncology, University of Toronto; Radiation Oncologist, Department of Radiation Oncology, Princess Margaret Hospital/University Health Network; 3. Professor, Department of Radiation Oncology, University of Toronto; Radiation Oncologist, Princess Margaret Hospital/University Health Network; Provincial Head, Radiation Treatment Program Cancer Care Ontario, Canada Abstract Prostate cancer is the sixth leading cause of cancer death among men worldwide. Risk stratification is used to facilitate the selection of optimal treatment approach; however, there is a lack of consensus in the prostate cancer risk-stratification systems. Furthermore, the term ‘locally advanced’ is often misused with high-risk disease. This poses problems when interpreting clinical trials and evaluating treatment outcomes. As a result the patients studied in clinical trials represent a heterogeneous population. The current standard care for locally advanced prostate cancer is a combination of radiotherapy (RT) and androgen deprivation therapy (ADT) and this is supported by several large randomized clinical trials. Long-term ADT is recommended but the optimal duration remains to be better defined. The use of newer and more potent hormonal agents appears to be promising, at least in the setting of metastatic castration-resistant disease, but their role in locally advanced disease remains undefined. This article will summarize the available literature concerning the recent development of hormone therapy in reference to locally advanced prostate cancer. As for the future, individualization of treatment and personalized cancer care is the trend. The availability and the use of improved cellular and/or molecular markers to better risk stratify prostate cancer patients will allow us to select the most effective therapy to enhance the overall outcome. Keywords Prostate cancer, locally advanced, radiotherapy, hormone therapy, androgen deprivation therapy, risk stratification, androgen receptor inhibitors, androgen synthesis inhibitors, degarelix, abiraterone acetate, enzalutamide, orteronel Disclosure: The authors have no conflicts of interests to declare. Received: February 3, 2014 Accepted: March 10, 2014 Citation: Oncology & Hematology Review, 2014;10(1):48–53 Correspondence: Padraig Warde, MB, MRCPI, FRCPC, Radiation Medicine Program, Princess Margaret Cancer Centre, 610 University Avenue, Toronto, Ontario, M5G 2M, Canada. E: padraig.warde@rmp.uhn.on.ca Prostate cancer is the second most common cause of cancer and the sixth leading cause of cancer death among men worldwide with an estimated 899,000 new cases and 258,000 new deaths in 2008. 1 Risk-stratification systems are used to assist with treatment selection, ensuring prognostic uniformity in clinical trials, and in the evaluation of treatment outcomes. Based on work by D’Amico et al., 2 the Genitourinary Radiation Oncologists of Canada (GUROC) developed a classification system for patients with localized/locally advanced disease based on T category, prostate specific antigen (PSA) level at diagnosis, and Gleason score. 3 High-risk disease is defined as the presence of any of these factors: cT3 or cT4 category, PSA >20 ng/ml, or Gleason score >8. The exact definition of high-risk prostate cancer at diagnosis remains controversial and this lack of consensus remains a barrier to comparing clinical outcomes of various institutional series and results of clinical trials. Table 1 provides a summary of definitions of high-risk disease from different consensus groups. 2–6 48 The term ‘high-risk disease’ is often incorrectly used to describe patients with locally advanced disease. As a result, the patients studied in clinical trials of high-risk prostate cancer represents a heterogeneous group, including those with clinically organ-confined disease (cT1/T2) with Gleason score 8–10 and/or PSA >20  ng/ml, and those with locally advanced disease (cT3/T4). The proportion of patients presenting with locally advanced disease at diagnosis has decreased in the past 20 years, largely as a result of widespread PSA screening; however, this presentation remains a common clinical problem and management remains controversial. Since the discovery of hormone dependence of prostate cancer by Dr Huggins in 1941, hormone therapy has become the mainstay of treatment in metastatic prostate cancer. 7 Hormone therapy now has an increasingly important role in earlier stages of prostate cancer and is the standard of care in locally advanced disease when used in combination with radiotherapy (RT). Over the past few years multiple new © Tou c h ME d i ca l ME d ia 2014