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Prostate Cancer State of the Art in Locally Advanced and Recurrent Non-metastatic Prostate Cancer Hema Vankayala, MD 1 and Ulka Vaishampayan, MD 2 1. Medical Oncologist, John D Dingell VA Medical Center, Wayne State University, Detroit; 2. Professor of Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, US Abstract Prostate cancer (PC) is the second leading cause of cancer-related death in men in the US. Biochemical relapse is a significant problem, due to the eventual progression to metastatic disease. It is also an opportunity to explore interventions that may have the potential to prevent or delay the occurrence of metastases. Multiple therapies with diverse mechanisms of action have become available for use in metastatic castrate- resistant PC and are currently under active investigation in the non-metastatic disease state. The intent of this article is to discuss currently approved therapy in localized and locally advanced PC and to review the state of the art in clinical management within this disease state. We also discuss the novel agents and targets in development, especially for recurrent, non-metastatic PC. Keywords Prostate cancer, PSA relapse, localized prostate cancer, locally advanced prostate cancer, castrate resistance Disclosure: Hema Vankayala, MD, and Ulka Vaishampayan, MD, have no conflicts of interest to declare. No funding was received in the publication of this article. Received: September 4, 2014 Accepted: October 20, 2014 Citation: Oncology & Hematology Review, 2014;10(2):123–32 Correspondence: Ulka Vaishampayan, MD, Professor of Oncology, Karmanos Cancer institute/Wayne State University, 4100 John R, 4233 HWCRC, Detroit MI 48201, US. E: Prostate cancer (PC) is the second most common malignancy in American men and the second leading cause of cancer-related death in men in the US. It is estimated that in 2014 nearly 233,000 men will be diagnosed with PC, with 29,480 dying from the disease. 1,2 The majority of them are diagnosed as a result of screening, so symptomatic presentation is unusual. Since the introduction of prostate-specific antigen (PSA) screening in US, more than 1.3 million men have been diagnosed with PC and one million of these have undergone treatment. 3 Over 95 % of PCs are adenocarcinomas and the median age at diagnosis is 66 years. As per the Surveillance, Epidemiology, and End Results (SEER) 18 database, 80 % have localized disease and only 12 % have regional disease at diagnosis. In the same database, 5-year survival rates vary significantly with stage and have been noted to be 100  % for localized and regional stage disease. The risk factors for PC are increasing age, African American descent, and a family history of PC. Localized Prostate Cancer The current clinical management of localized PC depends on the risk features associated with the cancer and a patient’s life expectancy. The cancer risk is dependent on the clinical stage, PSA, highest Gleason Score (GS), and disease burden. The prostate volume also affects the treatment choice in some situations. Treatment options vary from watchful waiting (WW) and active surveillance (AS), to radical prostatectomy (RP), external © To u ch MEd ica l MEdia 201 4 beam radiation therapy (EBRT), brachytherapy, cryoablation, androgen deprivation therapy (ADT), and high-intensity focused ultrasound. Treatment recommendations and selection are dependent on disease and patient characteristics, along with patient and physician preferences. Several studies have shown that patients with low-grade, localized PC have a low risk for clinical progression within the first 10 to 15 years of diagnosis, so AS and WW are reasonable options. This strategy is also best suited to men with a shorter life expectancy. 4–7 First-line ADT is seldom indicated in patients with localized PC. The outcomes of men treated with primary ADT, compared with those who were not, was evaluated in a large, retrospective cohort study. ADT is not associated with increased risk for all-cause mortality, or with reduced PC-specific mortality. However, the risk for PC progression on primary ADT was not studied. The likely explanation for the 40 % decline in PC- specific mortality during this time period is earlier detection and definitive curative intervention. ADT is not curative. This study re-affirms that ADT should be reserved for its established role: as palliation for metastatic PC, in men with node-positive PC after RP, or in combination with RT in intermediate- or high-risk PC. 8,9 The treatment options for low-risk and very-low-risk patients include AS, WW, or monotherapies such as interstitial prostate brachytherapy, RT, 123