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Prostate Cancer and Prostatic Diseases Dec 2016Treatment of high-risk prostate cancer has evolved considerably over the past two decades, yet patients with very-high-risk features may still experience poor outcome... (Review)
Review
BACKGROUND
Treatment of high-risk prostate cancer has evolved considerably over the past two decades, yet patients with very-high-risk features may still experience poor outcome despite aggressive therapy. We review the contemporary literature focusing on current definitions, role of modern imaging and treatment alternatives in very-high-risk prostate cancer.
METHODS
We searched the MEDLINE database for all clinical trials or practice guidelines published in English between 2000 and 2016, with the following search terms: 'prostatic neoplasms' (MeSH Terms) AND ('high risk' (keyword) OR 'locally advanced' (keyword) OR 'node positive' (keyword)). Abstracts pertaining to very-high-risk prostate cancer were evaluated and 40 pertinent studies served as the basis for this review.
RESULTS
The term 'very'-high-risk prostate cancer remains ill defined. The European Association of Urology and National Comprehensive Cancer Network guidelines provide the only available definitions, categorizing those with clinical stage T3-4 or minimal nodal involvement as very high risk irrespective of PSA level or biopsy Gleason score. Modern imaging with multiparametric magnetic resonance imaging and positron emission tomography-prostate-specific membrane antigen scans has a role in pre-treatment assessment. Local definitive therapy by external beam radiation combined with androgen deprivation is supported by several randomized clinical trials, whereas the role of surgery in the very-high-risk setting combined with adjuvant radiation/androgen deprivation therapy is emerging. Growing evidence suggest neoadjuvant taxane-based chemotherapy in the context of a multimodal approach may be beneficial.
CONCLUSIONS
Men with very-high-risk tumors may benefit from local definitive treatment in the setting of a multimodal regimen, offering local control and possibly cure in well selected patients. Further studies are necessary to better characterize the 'very'-high-risk category and determine the optimal therapy for the individual patient.
Topics: Androgen Antagonists; Clinical Trials as Topic; Humans; Male; Neoadjuvant Therapy; Prostatic Neoplasms; Radiotherapy, Adjuvant; Randomized Controlled Trials as Topic; Risk Factors
PubMed: 27618950
DOI: 10.1038/pcan.2016.40 -
Asia-Pacific Journal of Clinical... Jun 2019Men with prostate cancer with positive margins, extraprostatic extension, positive lymph nodes, high prostate-specific antigen, or high Gleason Score are at high risk of... (Review)
Review
Men with prostate cancer with positive margins, extraprostatic extension, positive lymph nodes, high prostate-specific antigen, or high Gleason Score are at high risk of recurrence following primary therapy. Androgen deprivation therapy (ADT), which includes medical/surgical castration, antiandrogen therapy, and combined androgen blockade, can be combined with primary therapy to shrink the tumor, reduce margin positivity, and reduce the risk of recurrence. However, many problems still remain, such as optimizing the application of ADT in the treatment of prostate cancer, for example, ideal patient population and optimal timing and duration of therapy. To investigate these problems, we searched PubMed for relevant publications on clinical studies of deprivation therapy for nonmetastatic prostate cancer. In this review, we discuss our findings on the role of ADT in the treatment of castrate-sensitive nonmetastatic prostate cancer and the adverse effects associated with ADT. We also examine the recent advances in new predictive biomarkers for ADT, many of which are currently in the exploratory phase. Overall, the addition of ADT to primary therapy improves outcomes for patients with intermediate- or high-risk prostate cancer.
Topics: Aged; Androgen Antagonists; Antineoplastic Agents; Humans; Male; Prostatic Neoplasms
PubMed: 30729683
DOI: 10.1111/ajco.13108 -
Expert Opinion on Pharmacotherapy Jun 2017Androgen deprivation therapy (ADT) is the mainstay for advanced, hormone-sensitive prostate cancer, and options include surgical castration, luteinizing... (Review)
Review
Androgen deprivation therapy (ADT) is the mainstay for advanced, hormone-sensitive prostate cancer, and options include surgical castration, luteinizing hormone-releasing hormone (LHRH) agonist, and more recently, gonadotropin releasing hormone (GnRH) antagonist therapy. Our understanding of the mechanisms and adverse effects of ADT has increased substantially, including the class-specific adverse effects of ADT. Areas covered: This review will summarize the pharmacodynamic and pharmacokinetic properties of the GnRH antagonist degarelix and its role in the management of advanced prostate cancer, the clinical evidence supporting its regulatory approval, as well as potential benefits and disadvantages over traditional LHRH agonist therapy. Expert opinion: Degarelix represents a newer class of ADT that results in a rapid and reliable decline in serum testosterone, a quality that makes it particularly advantageous in men presenting with symptomatic, hormone-sensitive prostate cancer. Due to differences in mechanism of action, there is observational data suggesting a potential cardiovascular and even oncologic benefit over traditional LHRH agonist therapy. Further research is ongoing to more clearly define this potential benefit.
Topics: Androgen Antagonists; Antineoplastic Agents, Hormonal; Drug-Related Side Effects and Adverse Reactions; Gonadotropin-Releasing Hormone; Humans; Male; Oligopeptides; Orchiectomy; Prostatic Neoplasms; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 28480768
DOI: 10.1080/14656566.2017.1328056 -
The Oncologist Mar 2024In the ARASENS trial (NCT02799602), darolutamide in combination with androgen-deprivation therapy (ADT) and docetaxel significantly reduced the risk of death by 32.5%...
BACKGROUND
In the ARASENS trial (NCT02799602), darolutamide in combination with androgen-deprivation therapy (ADT) and docetaxel significantly reduced the risk of death by 32.5% (HR, 0.68; 95% CI, 0.57-0.80; P < .0001) compared with placebo plus ADT with docetaxel in patients with metastatic hormone-sensitive prostate cancer (mHSPC). We present efficacy and safety of darolutamide versus placebo in Black patients from ARASENS.
PATIENTS AND METHODS
Patients with mHSPC were randomized 1:1 to darolutamide 600 mg or placebo twice daily in combination with ADT and docetaxel. The primary endpoint was overall survival. Key secondary endpoints included time to castration-resistant prostate cancer (CRPC) and safety.
RESULTS
In ARASENS, 54 Black patients received darolutamide (n = 26) or placebo (n = 28) plus ADT and docetaxel. In Black patients, overall survival favored darolutamide versus placebo (median, not reached vs. 38.7 months; stratified HR, 0.41; 95% CI, 0.17-1.02), with 4-year survival rates of 62% versus 41%. The darolutamide group also had longer time to CRPC compared with the placebo group (median, not reached vs .12.6 months; HR, 0.09; 95% CI, 0.02-0.30). The safety profile of darolutamide in Black patients was consistent with that observed for the overall ARASENS population (grade 3/4 treatment-emergent adverse events, TEAEs: 61.5% vs. 66.1%; serious TEAEs: 42.3% vs. 44.8%).
CONCLUSION
In this small population of Black patients with mHSPC from the ARASENS trial, darolutamide was associated with an improvement in survival and time to CRPC and was well tolerated. Efficacy and safety findings in Black patients were consistent with the overall ARASENS population.
Topics: Humans; Male; Androgen Antagonists; Antineoplastic Combined Chemotherapy Protocols; Docetaxel; Prostatic Neoplasms; Prostatic Neoplasms, Castration-Resistant; Pyrazoles; Randomized Controlled Trials as Topic
PubMed: 37812679
DOI: 10.1093/oncolo/oyad254 -
Medical Sciences (Basel, Switzerland) Feb 2022Prostate cancer (PCa) is the second most common cancer in men. Common treatments include active surveillance, surgery, or radiation. Androgen deprivation therapy and... (Review)
Review
Prostate cancer (PCa) is the second most common cancer in men. Common treatments include active surveillance, surgery, or radiation. Androgen deprivation therapy and chemotherapy are usually reserved for advanced disease or biochemical recurrence, such as castration-resistant prostate cancer (CRPC), but they are not considered curative because PCa cells eventually develop drug resistance. The latter is achieved through various cellular mechanisms that ultimately circumvent the pharmaceutical's mode of action. The need for novel therapeutic approaches is necessary under these circumstances. An alternative way to treat PCa is by repurposing of existing drugs that were initially intended for other conditions. By extrapolating the effects of previously approved drugs to the intracellular processes of PCa, treatment options will expand. In addition, drug repurposing is cost-effective and efficient because it utilizes drugs that have already demonstrated safety and efficacy. This review catalogues the drugs that can be repurposed for PCa in preclinical studies as well as clinical trials.
Topics: Androgen Antagonists; Drug Repositioning; Drug Resistance; Humans; Male; Prostatic Neoplasms, Castration-Resistant
PubMed: 35225948
DOI: 10.3390/medsci10010015 -
The Israel Medical Association Journal... Mar 2022Increased life expectancy due to improved cancer prognosis, shared determinants (e.g., tobacco use), and cardiovascular toxicities related to cancer therapies, including... (Review)
Review
Increased life expectancy due to improved cancer prognosis, shared determinants (e.g., tobacco use), and cardiovascular toxicities related to cancer therapies, including the adverse cardiometabolic effects of androgen deprivation therapy for prostate cancer, make cardiovascular disease an frequent and important co-morbidity in patients with a genitourinary malignancy. Complex cardiovascular disease can pose significant challenges in the management of these patients given the uncertainties related to the best approach to reconcile ischemic and bleeding risks, and the role of invasive cardiovascular interventions in individuals with advanced cancer. In this review, we discuss the current evidence that informs decision-making in this clinical context.
Topics: Androgen Antagonists; Cardiologists; Cardiovascular Diseases; Humans; Male; Prostatic Neoplasms; Urogenital Neoplasms
PubMed: 35347931
DOI: No ID Found -
International Journal of Environmental... Mar 2022Loss of muscle mass and muscle function is a common side effect from androgen deprivation therapy (ADT) for prostate cancer (PCa). Here, we explored effects of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Loss of muscle mass and muscle function is a common side effect from androgen deprivation therapy (ADT) for prostate cancer (PCa). Here, we explored effects of heavy-load resistance training (RT) on lean body mass and muscle strength changes reported in randomized controlled trials (RCTs) among PCa patients on ADT and in healthy elderly men (HEM), by comparison of results in separate meta-analysis.
METHODS
RCTs were identified through databases and reference lists.
RESULTS
Seven RCTs in PCa patients ( = 449), and nine in HEM ( = 305) were included. The effects of RT in lean body mass change were similar among PCa patients (Standardized mean difference (SMD): 0.4, 95% CI: 0.2, 0.7) and HEM (SMD: 0.5, 95% CI: 0.2, 0.7). It is noteworthy that the within group changes showed different patterns in PCa patients (intervention: 0.2 kg; control: -0.6 kg) and HEM (intervention: 1.2 kg; control: 0.2 kg). The effects of RT on change in muscle strength (measured as 1 RM) were similar between PCa patients and HEM, both for lower body- (PCa: SMD: 1.9, 95% CI: 1.2, 2.5; HEM: SMD: 2.2, 95% CI: 1.0, 3.4), and for upper body exercises (PCa: SMD: 2.0, 95% CI: 1.3, 2.7; HEM: SMD: 1.9, 95% CI: 1.3, 2.6).
CONCLUSIONS
The effects of RT on lean body mass and 1 RM were similar in PCa patients on ADT and HEM, but the mechanism for the intervention effect might differ between groups. It seems that RT counteracts loss of lean body mass during ADT in PCa patients, as opposed to increasing lean body mass in HEM.
Topics: Adaptation, Physiological; Aged; Androgen Antagonists; Androgens; Humans; Male; Prostatic Neoplasms; Resistance Training
PubMed: 35409505
DOI: 10.3390/ijerph19073820 -
Journal For Immunotherapy of Cancer Mar 2022Prostate cancer (PC) responds to androgen deprivation therapy (ADT) usually in a transient fashion, progressing from hormone-sensitive PC (HSPC) to castration-resistant...
BACKGROUND
Prostate cancer (PC) responds to androgen deprivation therapy (ADT) usually in a transient fashion, progressing from hormone-sensitive PC (HSPC) to castration-resistant PC (CRPC). We investigated a mouse model of PC as well as specimens from PC patients to unravel an unsuspected contribution of thymus-derived T lymphocytes and the intestinal microbiota in the efficacy of ADT.
METHODS
Preclinical experiments were performed in PC-bearing mice, immunocompetent or immunodeficient. In parallel, we prospectively included 65 HSPC and CRPC patients (Oncobiotic trial) to analyze their feces and blood specimens.
RESULTS
In PC-bearing mice, ADT increased thymic cellularity and output. PC implanted in T lymphocyte-depleted or athymic mice responded less efficiently to ADT than in immunocompetent mice. Moreover, depletion of the intestinal microbiota by oral antibiotics reduced the efficacy of ADT. PC reduced the relative abundance of in the gut, and this effect was reversed by ADT. Moreover, cohousing of PC-bearing mice with tumor-free mice or oral gavage with improved the efficacy of ADT. This appears to be applicable to PC patients because long-term ADT resulted in an increase of thymic output, as demonstrated by an increase in circulating recent thymic emigrant cells (sjTRECs). Moreover, as compared with HSPC controls, CRPC patients demonstrated a shift in their intestinal microbiota that significantly correlated with sjTRECs. While feces from healthy volunteers restored ADT efficacy, feces from PC patients failed to do so.
CONCLUSIONS
These findings suggest the potential clinical utility of reversing intestinal dysbiosis and repairing acquired immune defects in PC patients.
Topics: Androgen Antagonists; Androgens; Animals; Gastrointestinal Microbiome; Humans; Immune System; Male; Mice; Prostatic Neoplasms, Castration-Resistant
PubMed: 35296557
DOI: 10.1136/jitc-2021-004191 -
European Journal of Cancer (Oxford,... Oct 2023In patients with non-metastatic castration-resistant prostate cancer (nmCRPC) in the Androgen Receptor Antagonizing Agent for Metastasis-free Survival (ARAMIS) trial,... (Randomized Controlled Trial)
Randomized Controlled Trial
Efficacy and safety outcomes of darolutamide in patients with non-metastatic castration-resistant prostate cancer with comorbidities and concomitant medications from the randomised phase 3 ARAMIS trial.
PURPOSE
In patients with non-metastatic castration-resistant prostate cancer (nmCRPC) in the Androgen Receptor Antagonizing Agent for Metastasis-free Survival (ARAMIS) trial, darolutamide significantly improved median metastasis-free survival by nearly 2 years and reduced the risk of death by 31% versus placebo, with a favourable safety/tolerability profile. This post hoc analysis of ARAMIS evaluated efficacy and safety in patients by number of comorbidities and concomitant medications.
METHODS
Patients with nmCRPC were randomised 2:1 to darolutamide (n = 955) or placebo (n = 554) while continuing androgen-deprivation therapy. Overall survival (OS) and treatment-emergent adverse events (TEAEs) were evaluated in subgroups by median numbers of ongoing comorbidities and concomitant medications. HRs were determined from univariate analysis using Cox regression.
FINDINGS
Median numbers of comorbidities and concomitant medications were 6 and 10, respectively, with 41.6% of patients having >6 comorbidities and 48.8% taking >10 concomitant medications. For patients with ≤ 6 and >6 comorbidities, darolutamide increased OS versus placebo (hazard ratio [HR] 0.65 and 0.73, respectively), and this benefit was consistent for cardiovascular, metabolic, and other comorbidities (HR range: 0.39-0.88). For patients taking ≤ 10 and >10 concomitant medications, increased OS was also observed with darolutamide versus placebo (HR 0.76 and 0.66, respectively), and the benefit was consistent across medication classes (HR range: 0.45-0.80). Incidences of TEAEs and TEAEs leading to treatment discontinuation with darolutamide were similar to placebo across subgroups by numbers of comorbidities and concomitant medications.
CONCLUSIONS
The OS benefit and safety of darolutamide remained consistent with that observed in the overall ARAMIS population, even in patients with high numbers of comorbidities or concomitant medications.
GOV REGISTRATION
NCT02200614.
TWEETABLE ABSTRACT
Darolutamide increased overall survival versus placebo, and incidences of most adverse events were similar between treatments in patients with ≤ 6 or >6 comorbidities and those taking ≤ 10 or >10 concomitant medications.
Topics: Male; Humans; Androgen Antagonists; Prostatic Neoplasms, Castration-Resistant; Pyrazoles; Patients
PubMed: 37660438
DOI: 10.1016/j.ejca.2023.113258 -
Asian Journal of Andrology 2015Radiotherapy (XRT) is a curative treatment option for prostate cancer (PCa). Recent XRT technologies allow higher dose therapy that lead to increased local control with... (Review)
Review
Radiotherapy (XRT) is a curative treatment option for prostate cancer (PCa). Recent XRT technologies allow higher dose therapy that lead to increased local control with less adjacent tissue damage. Additionally, receiving neo-adjuvant or adjuvant hormonotherapy (HT) during radiation therapy increases the curative effect. The aim of this paper is to review the current literature and guidelines on external beam radiation therapy for PCa. However, brachytherapy and radiosurgery, a recently evolving relatively new technology for the radiotherapeutic management of localized PCa, are beyond the scope of this paper.
Topics: Adenocarcinoma; Androgen Antagonists; Antineoplastic Agents, Hormonal; Chemoradiotherapy, Adjuvant; Humans; Male; Patient Selection; Prostatectomy; Prostatic Neoplasms; Radiation Dosage; Radiotherapy Planning, Computer-Assisted; Radiotherapy, Adjuvant
PubMed: 26112487
DOI: 10.4103/1008-682X.156857