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Metastatic hormone sensitive prostate cancer

Harsh Shah, Ulka Vaishampayan
With the decrease in PSA screening based on the 2011 United States Preventive Services Task Force guidelines and the potential approval of highly sensitive imaging techniques over the next few years, we are likely to see an increasing trend of metastatic prostate cancer diagnosis. Traditional therapy for nonmetastatic prostate cancer (nmPC) has consisted of androgen deprivation therapy (ADT) followed by other hormonal therapy maneuvers, such as anti-androgen withdrawal, herbal preparations, low dose steroids, or ketoconazole...
December 7, 2018: Targeted Oncology
Oliver Sartor
The management of advanced prostate cancer today follows a multidisciplinary approach and involves multi-target treatments. The paradigm has shifted from traditional hormonal therapy, surgery and radiation, to the use of chemotherapy, and until recently the development of various immunotherapies and radiopharmaceuticals. Recent advances turn to molecular medicine combining the expertise of molecular pathology and genetics. In this review, germline genetics, advances in castrate-sensitive metastatic disease, androgen receptor alterations, potential new targeted therapy and novel radiopharmaceuticals will be discussed as the newest perspectives for treating prostate cancer...
November 2018: Asia-Pacific Journal of Clinical Oncology
Jeremy Yuen-Chun Teoh, Chi-Fai Ng, Darren Ming-Chun Poon
The treatment of metastatic hormone-sensitive prostate cancer (mHSPC) has been rapidly evolving. In the past, the use of chemotherapy was reserved for metastatic prostate cancer patients who developed castration resistance. Subsequently, there were three well-designed randomized controlled trials investigating the use of chemotherapy together with androgen deprivation therapy as the first-line treatment for metastatic hormone-sensitive prostate cancer. The GETUG-AFU 15 study was a negative trial, but the subsequent CHAARTED and STAMPEDE studies demonstrated magnificent survival benefit in the mHSPC setting...
November 2018: Asia-Pacific Journal of Clinical Oncology
Alexander Kretschmer, Tilman Todenhöfer
Combinations of conventional androgen deprivation therapy (ADT) with docetaxel or abiraterone have shown encouraging results in several phase 3 randomized trials and were consequently implemented in current clinical guidelines. However, to date it is still not clear which patients benefit the most from combination therapy and whether there are still patients who are candidates for ADT monotherapy. Here we highlight evidence that indications for conventional ADT have been significantly reduced over the past years and should only be offered to highly selected patients...
November 24, 2018: European Urology Focus
Ye Yuan, Amar U Kishan, Nicholas G Nickols
The cornerstone of treatment for metastatic prostate cancer patients has been conventional androgen deprivation therapy, with additional systemic therapy initiated only after castration resistance, and local therapy reserved for palliation. Compelling results from modern trials challenge this paradigm, arguing for initiating escalated hormone therapy and/or chemotherapy during the castration-sensitive disease state for many patients. Furthermore, modern radiotherapy techniques allow for local control of disease with low risk of toxicity...
November 19, 2018: World Journal of Urology
Jeremy Y C Teoh, Darren M C Poon, Daisy Lam, Tim Chan, Michelle F T Chan, Eric K C Lee, Snow Law, Kuen Chan, Nicole M Cheng, Kai-Man Lai, Chi-Ho Leung, Chi-Fai Ng
BACKGROUND: There is a lack of real-world data regarding the treatment outcomes of chemohormonal therapy versus hormonal therapy alone in Chinese men with metastatic hormone-sensitive prostate cancer. PATIENTS AND METHODS: We conducted a territory-wide, multicenter, age- and prostate-specific antigen (PSA)-matched cohort study comparing chemohormonal therapy and hormonal therapy alone in Chinese men with metastatic hormone-sensitive prostate cancer. Patient and disease characteristics were reviewed...
October 27, 2018: Clinical Genitourinary Cancer
Ken Chow, Patrick McCoy, Ryan Stuchbery, Niall M Corcoran, Christopher M Hovens
PURPOSE: To review the current understanding and recent developments regarding the concept of oligometastases in hormone-sensitive prostate cancer. METHODS: A comprehensive literature search of electronic databases, including PubMed and Embase was conducted for the search term 'oligometastases' in combinations with 'prostate cancer', 'hormone sensitive', 'genetics', and 'molecular'. All articles relating to these search terms have been taken into account. RESULTS: Prostate cancer remains a major cause of morbidity and mortality worldwide...
October 31, 2018: World Journal of Urology
Chad Ritch, Michael Cookson
Advanced prostate cancer includes a wide spectrum of disease ranging from hormone naïve or hormone sensitive to castration resistant, both containing populations of men who have demonstrable metastatic and non-metastatic states. The mainstay of treatment for metastatic hormone-sensitive prostate cancer is androgen deprivation therapy (ADT). However, recent level 1 evidence demonstrates that the addition of chemotherapy or abiraterone acetate to ADT results in significant survival advantage as compared with ADT alone...
2018: F1000Research
Emmanuel S Antonarakis, Farah Shaukat, Pedro Isaacsson Velho, Harsimar Kaur, Eugene Shenderov, Drew M Pardoll, Tamara L Lotan
Mismatch repair (MMR) gene mutations are rare in prostate cancer, and their histological and clinical characteristics are largely unknown. We conducted a retrospective study to explore disease characteristics and treatment outcomes of men with metastatic prostate cancer harboring germline and/or somatic MMR mutations detected using clinical-grade genomic assays. Thirteen patients with a deleterious MMR gene mutation were identified. Median age was 64 yr, 75% had grade group 5 (Gleason sum 9 or 10), 23% had intraductal histology, 46% had metastatic disease at initial diagnosis, and 31% had visceral metastases...
October 15, 2018: European Urology
Niranjan J Sathianathen, Yiannis A Philippou, Gretchen M Kuntz, Badrinath R Konety, Shilpa Gupta, Alastair D Lamb, Philipp Dahm
BACKGROUND: There has been considerable development in the treatment of advanced prostate cancer over the last decade. A number of agents, including docetaxel, cabazitaxel, abiraterone acetate, enzalutamide and sipuleucel-T, have been reported to improve outcomes in men with castration-resistant disease and their use is being explored in hormone-sensitive prostate cancer. OBJECTIVES: To assess the effects of early taxane-based chemohormonal therapy for newly diagnosed, metastatic, hormone-sensitive prostate cancer...
October 15, 2018: Cochrane Database of Systematic Reviews
Giulia Baciarello, Marco Gizzi, Karim Fizazi
Prostate cancer is the second most common cause of cancer worldwide and is the most frequently detected cancer in the European Union in men over 50 years of age. Androgen deprivation therapy remains the cornerstone of treatment for recurrent or metastatic disease. Unfortunately, nearly all patients will develop resistance to androgen blockade leading to castration-resistant prostate cancer (CRPC). Over the last 10 years, new treatments have dramatically improved overall survival of men with mCRPC. Current therapies are based on AR-axis inhibitors and taxane-based chemotherapies, as well as radiopharmaceuticals and Sipuleucel T...
November 2018: Expert Opinion on Pharmacotherapy
Zsófia Küronya, Krisztina Bíró, Lajos Géczi, Anikó Maráz
The treatment of metastatic prostate cancer can be divided into two pathophysiological phases: hormone-sensitive and castration-resistant phases. Huggins' observation in the year 1941, which was awarded with the Nobel Prize in 1966, has a key role in treatment during the hormone-sensitive phase, stating that if the testicles are removed, the size of the prostate cancer decreases. Inducing androgen deprivation, i.e., testosterone depletion is the basic treatment of metastatic prostate cancer that patients have to receive life-long...
October 2018: Orvosi Hetilap
Helle D Zacho, Lars J Petersen
A 69-year-old man with newly diagnosed prostate cancer PSA 274 ng/mL, Gleason 4+3, T-stage 3b) underwent Ga-PSMA PET/CT for staging with follow-up scans 6 and 13 weeks after androgen deprivation therapy (ADT) initiation. Six weeks after ADT initiation, lymph node metastases observed at staging showed metabolic and radiological regression, whereas the skeleton showed increased PSMA uptake in existing bone metastases and several new PSMA-avid lesions. Skeletal PSMA uptake decreased after 13 weeks of ADT, and prostate-specific antigen decreased to 16 ng/mL...
November 2018: Clinical Nuclear Medicine
Susan Feyerabend, Fred Saad, Tracy Li, Tetsuro Ito, Joris Diels, Suzy Van Sanden, Peter De Porre, Julie Roiz, Seye Abogunrin, Maria Koufopoulou, Karim Fizazi
AIM: Androgen deprivation therapy (ADT) has long been the gold standard for patients with metastatic hormone-sensitive prostate cancer (mHSPC). Clinical trials have demonstrated significant survival benefits when docetaxel (DOC) or abiraterone acetate (AA) and prednisone (P) are added to ADT, necessitating comparison of these combination treatments. METHODS: A systematic review of randomised controlled trials (RCTs) of AA-/ADT-/DOC-containing treatment regimens in newly diagnosed patients with high-risk and/or high-volume mHSPC identified three RCTs (LATITUDE, CHAARTED and GETUG-AFU 15)...
November 2018: European Journal of Cancer
Karim Fizazi, Matthew R Smith, Bertrand Tombal
Prostate cancer (PC) is the second most common cancer in men and is the fifth leading cause of cancer-related deaths among men. Androgen receptor (AR) signaling plays a key role in PC tumor growth and progression, with androgens stimulating PC proliferation and survival. Castration-resistant PC (CRPC) is characterized by increasing levels of prostate-specific antigen or radiographic progression despite androgen-deprivation therapy (ADT). In most patients, castration resistance results from aberrations in AR or the AR signaling pathway...
October 2018: Clinical Genitourinary Cancer
Neil M Schultz, Scott C Flanders, Samuel Wilson, Bruce A Brown, Yan Song, Hongbo Yang, Stanislav Lechpammer, Vahan Kassabian
INTRODUCTION: Enzalutamide and abiraterone acetate (plus prednisone) are new hormonal treatments for metastatic castration-resistant prostate cancer (mCRPC). This study compared treatment duration, healthcare resource utilization (HRU), and treatment costs for chemotherapy-naïve mCRPC patients treated with enzalutamide or abiraterone acetate in the USA. METHODS: Chemotherapy-naïve mCRPC patients initiating treatment with enzalutamide or abiraterone acetate were identified from administrative claims...
October 2018: Advances in Therapy
Roberto Iacovelli, Chiara Ciccarese, Claudia Mosillo, Davide Bimbatti, Emanuela Fantinel, Lisa Stefani, Michele Simbolo, Mario Romano, Renzo Mazzarotto, Matteo Brunelli, Emilio Bria, Aldo Scarpa, Rita T Lawlor, Walter Artibani, Giampaolo Tortora
BACKGROUND: The CHAARTED and LATITUDE trials demonstrated improved outcomes with docetaxel or abiraterone plus androgen deprivation therapy in metastatic hormone sensitive prostate cancer (mHSPC) using two different prognostic scores. OBJECTIVE: The aim of our study was to assess the concordance between the two scores and if these retained their prognostic value exclusively in de novo mHSPC. PATIENTS AND METHODS: De novo mHSPC patients referring to our institution were retrospectively stratified according to the CHAARTED and LATITUDE classifications: high volume/high risk (HV/HR), low-volume/low-risk (LV/LR), and HVorHR (HV/LR and LV/HR)...
October 2018: Targeted Oncology
Stefan Aufderklamm, Jörg Hennenlotter, Phillip Leidenberger, Steffen Rausch, Andrea Hohneder, Ursula Kühs, Moritz Maas, Christian Schwentner, Jens Bedke, Arnulf Stenzl, Tilman Todenhöfer
Purpose: Dickkopf-1 (DKK-1) and sclerostin seem to inhibit osteoblast activity by blocking the Wnt pathway, which leads to progression of metastatic prostate cancer (PC). However, it is unknown whether serum levels of these proteins are altered in PC patients with or without metastasis. The aim of this study was to assess DKK-1 and sclerostin serum levels in PC patients, including patients with bone metastases. Methods: The study cohort ( N = 143) consisted of 53 controls with benign prostatic hyperplasia (BPH), 43 with localized PC (PC cM0), and 47 had PC with metastasis (PC cM1)...
2018: Disease Markers
Lai Xu, Russell K Pachynski
PURPOSE OF REVIEW: Androgen deprivation therapy (ADT) has been the standard-of-care (SOC) for metastatic hormone-sensitive prostate cancer (mHSPC) since the middle of the twentieth century. Recently, several practice-changing trials have added new therapy options for these patients. Here we review these studies and discuss guidelines on treatment decision-making. RECENT FINDINGS: A trio of studies (GETUG-AFU15, STAMPEDE, CHAARTED) combining docetaxel chemotherapy with ADT all showed clinical benefit of the addition...
August 13, 2018: Current Urology Reports
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