Metastatic hormone sensitive prostate cancer

Androgen deprivation therapy (ADT) has been the standard of care for the last 75 years in metastatic hormone sensitive prostate cancer (PCa). However, this approach is rarely curative. Recent clinical trials have demonstrated that ADT combined with other agents, notably docetaxel and abiraterone, lead to improved survival. The mechanisms surrounding this improved cancer outcomes are incompletely defined. The response of cancer cells to ADT includes apoptosis and cell death, but a significant fraction remains viable...

PURPOSE: Contemporary treatment for metastatic hormone sensitive prostate cancer (mHSPC) includes androgen deprivation therapy (ADT) plus abiraterone or docetaxel. While these intensified regimens have improved efficacy, they are also associated with increased cost and toxicities. Not all men with mHSPC may be candidates for these intensified regimens, yet there are no clinical models or biomarkers used to optimize treatment selection. Herein, we hypothesized that longer time from prior definitive therapy (DT), either radical prostatectomy, definitive radiotherapy, or both, to onset of metastatic disease is associated with improved survival outcomes in men with newly diagnosed mHSPC...

PURPOSE: To capture UK societal health utility values for high-risk metastatic hormone-sensitive prostate cancer (mHSPC) and the disutility associated with treatment-related adverse events (AEs) to inform future cost-utility analyses. METHODS: A literature review, and patient and clinical expert interviews informed the development of health states characterising mHSPC symptoms and the impact of treatment-related AEs on health-related quality of life (HRQL). Three base health states were developed describing a typical patient with high-risk mHSPC: receiving androgen deprivation therapy (ADT) [Base State 1]; receiving docetaxel plus ADT [Base State 2]; completed docetaxel and still receiving ADT whose disease has not yet progressed [Base State 3]...

OBJECTIVES: Androgen deprivation therapy (ADT) has historically been the main management option for men with metastatic, hormone-sensitive prostate cancer. Over the last two decades, a number of agents have demonstrated a benefit in castration-resistant disease[1] and there has been interest to employ these drugs earlier in the disease course when the cancer is hormone-sensitive. Taxane-based chemotherapy has been utilized in such a manner and we aimed to assess the effects of early taxane-based chemohormonal therapy for newly diagnosed, metastatic, hormone-sensitive prostate cancer...

PURPOSE: Androgen deprivation therapy(ADT) alone has been the standard of care for metastatic hormone sensitive prostate cancer(mHSPC) for the last 75 years. This review focuses on recent trials and mechanisms that highlight a new paradigm, combining ADT with other agents, changing the management of prostate cancer patients with advanced disease. METHODS: A PubMed and Web of Science database search on peer-reviewed literature was performed through January 2018 using the keywords "metastatic hormone sensitive prostate cancer", " metastatic castration sensitive prostate cancer", "docetaxel", "abiraterone" and "senescence in cancer"...

PURPOSE: The Oncology Care Model (OCM) must be clinically relevant, accurate, and comprehensible to drive value-based care. METHODS: We studied OCM data detailing observed and expected expenses for 6-month-long episodes of care for patients with prostate cancer. We constructed seven disease state-treatment dyads into which we grouped each episode on the bases of diagnoses, procedures, and medications in OCM claims data. We used this clinical-administrative stratification model to facilitate a comparative cost analysis, and we evaluated emergency department and hospital utilization and drug therapy as potential drivers of cost...

Patients with metastasis prostate cancer underwent androgen deprivation therapy (ADT) in the considering of the leading role of androgen receptor pathway. However, the resistance occurred within 1 year or more. The combination of cytotoxic chemotherapy and abiraterone for ADT therapy was performed in recent randomized controlled trials. The meta-analysis was focused on the treatment comparisons between additional treatment with ADT and ADT alone. A significant difference was observed that the overall survival benefit of early and active additional treatment with ADT in patients with hormone-sensitive metastatic prostate cancer...

There are many ongoing randomised trials of promising therapies for metastatic hormone-sensitive prostate cancer (mHSPC), but standard systematic reviews may not synthesise these in a timely or reliable way. We demonstrate how a novel approach to evidence synthesis is being used to speed up and improve treatment evaluations for mHSPC. This more prospective, dynamic, and collaborative approach to systematic reviews of both trial results and individual participant data (IPD) is helping in establishing quickly and reliably which treatments are most effective and for which men...

BACKGROUND: Our study aimed to analyze the potential association between clinical parameters and ERG expression and the outcome of docetaxel chemotherapy among patients with metastatic hormone-sensitive prostate cancer. PATIENTS AND METHODS: Fifty-five patients with metastatic hormone-sensitive prostate cancer were treated with docetaxel in addition to androgen deprivation therapy. Patient characteristics, clinical factors, and tumor expression of ERG by immunohistochemistry were analyzed with respect to therapeutic response and survival data...

More than a million men worldwide are diagnosed with prostate cancer every year. After androgen deprivation therapy (ADT), chemotherapy has been the only subsequent intervention to improve survival in the metastatic setting but has limitations for patients who may not tolerate its toxicity profile or are not candidates on the basis of comorbidities. Novel anti-androgens such as abiraterone acetate have shown promise for such patients. This review draws on clinical evidence and experience to identify abiraterone as a well-tolerated, effective alternative to docetaxel...

Management of metastatic or advanced prostate cancer has acquired several therapeutic approaches that have drastically changed the course of the disease. In particular due to the high sensitivity of prostate cancer cells to hormone depletion, several agents able to inhibit hormone production or binding to nuclear receptor have been evaluated and adopted in clinical practice. However, despite several hormonal treatments being available nowadays for the management of advanced or metastatic prostate cancer, the natural history of the disease leads inexorably to the development of resistance to hormone inhibition...

INTRODUCTION: Various treatment options are available for metastatic hormone-sensitive prostate cancer. This study aimed to quantify how men with prostate cancer in the United Kingdom (UK), Germany, and Spain perceive the risks and benefits of hypothetical abiraterone acetate plus prednisone treatment and docetaxel-based chemotherapy treatment options. METHODS: A targeted literature review, exploratory interviews with prostate cancer patients and oncologists, and pre-test interviews were used to develop a discrete choice experiments (DCE)...

BACKGROUND: Patients with newly diagnosed non-metastatic prostate adenocarcinoma are typically classified as at low, intermediate, or high risk of disease progression using blood prostate-specific antigen concentration, tumour T category, and tumour pathological Gleason score. Classification is used to both predict clinical outcome and to inform initial management. However, significant heterogeneity is observed in outcome, particularly within the intermediate risk group, and there is an urgent need for additional markers to more accurately hone risk prediction...

Prostate cancer remains a leading cause of cancer-related death in men. Concurrently, the incidence of metastatic hormone-sensitive prostate cancer (mHSPC) at diagnosis has significantly risen as a result, in part, of recent advances in imaging. Given the increased utilization of prostate-specific membrane antigen-targeted positron emission tomography imaging and other modalities with improved accuracy in the detection of cancer, combined with changes in screening and other secular trends, more men get diagnosed at an oligometastatic stage in which timely treatment may improve survival...

In recent years, therapeutic advances, together with new medication sequences and combinations, have improved outcomes for prostate cancer. For a long time, androgen deprivation therapy (ADT) has been the standard of care for newly diagnosed, metastatic prostate cancer, first as a standalone therapy and then in combination with taxane-based regimens. More recently, the addition of abiraterone acetate to ADT to achieve complete androgen blockade has proven beneficial for the treatment of metastatic hormone-resistant prostate cancer and metastatic hormone-sensitive prostate cancer (mHSPC)...

Prostate specific membrane antigen (PSMA) may be targeted for both diagnostic and therapeutic purposes in the management of prostate cancer (PCa). In pre-clinical models, androgen blockade (AB) increases expression of PSMA in both hormone sensitive and castrate resistant xenotypes. The aim of this study was to evaluate the effect of AB treatment on Ga68PSMA-11 PET imaging in hormone naive (Luteinising hormone-releasing hormone (LHRH) ± bicalutamide), and in castrate resistant men (enzalutamide or abiraterone) with metastatic PCa...

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...

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...

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...

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...