Male ; Humans ; Prostatic Neoplasms/pathology* ; Prostatic Neoplasms, Castration-Resistant/pathology* ; Hormones ; Androgen Antagonists/therapeutic use*

The final analysis of the phase 3 Targeted Investigational Treatment Analysis of Novel Anti-androgen (TITAN) trial showed improvement in overall survival (OS) and other efficacy endpoints with apalutamide plus androgen deprivation therapy (ADT) versus ADT alone in patients with metastatic castration-sensitive prostate cancer (mCSPC). As ethnicity and regional differences may affect treatment outcomes in advanced prostate cancer, a post hoc final analysis was conducted to assess the efficacy and safety of apalutamide in the Asian subpopulation. Event-driven endpoints were OS, and time from randomization to initiation of castration resistance, prostate-specific antigen (PSA) progression, and second progression-free survival (PFS2) on first subsequent therapy or death. Efficacy endpoints were assessed using the Kaplan-Meier method and Cox proportional-hazards models without formal statistical testing and adjustment for multiplicity. Participating Asian patients received once-daily apalutamide 240 mg ( n = 111) or placebo ( n = 110) plus ADT. After a median follow-up of 42.5 months and despite crossover of 47 placebo recipients to open-label apalutamide, apalutamide reduced the risk of death by 32% (hazard ratio [HR]: 0.68; 95% confidence interval [CI]: 0.42-1.13), risk of castration resistance by 69% (HR: 0.31; 95% CI: 0.21-0.46), PSA progression by 79% (HR: 0.21; 95% CI: 0.13-0.35) and PFS2 by 24% (HR: 0.76; 95% CI: 0.44-1.29) relative to placebo. The outcomes were comparable between subgroups with low- and high-volume disease at baseline. No new safety issues were identified. Apalutamide provides valuable clinical benefits to Asian patients with mCSPC, with an efficacy and safety profile consistent with that in the overall patient population.
Male ; Humans ; Prostatic Neoplasms/pathology* ; Androgen Antagonists/therapeutic use* ; Prostate-Specific Antigen ; Castration ; Prostatic Neoplasms, Castration-Resistant/drug therapy*

Prostate cancer is the most common malignancy in the reproductive system of older males. Androgen deprivation therapy (ADT) is an important treatment for prostate cancer patients. However, almost all prostate cancer patients unavoidably progress to the castration-resistant stage after ADT treatment. Recent studies have shown that tumor-associated immune cells play major roles in the initiation, progression, and metastasis of prostate cancer. Various phenotypes of tumor-associated immune cells have tumor-promoting or antitumor functions mediated by interacting with tumor cells. Here, we review the current knowledge of tumor-associated immune cells in prostate cancer.
Disease Progression ; Humans ; Lymphocytes, Tumor-Infiltrating/pathology* ; Macrophages/pathology* ; Male ; Neutrophils/pathology* ; Prostatic Neoplasms/therapy* ; Prostatic Neoplasms, Castration-Resistant/therapy*

The standard first-line treatment of castration-resistant prostate cancer (CRPC) is docetaxel-based chemotherapy. However, CRPC may not respond to docetaxel due to drug resistance or other causes. Several new therapeutic agents have been developed, some of which are approved by FDA or on clinical trials. The mechanisms of action of these agents include stabilizing microtubules, inhibiting hormone synthesis, blocking androgen receptor, bone targeting or immune regulation. In this article we review the novel therapeutic options for CPRC after docetaxel failure.
Bone Neoplasms ; drug therapy ; secondary ; Drug Resistance, Neoplasm ; Humans ; Male ; Prostatic Neoplasms, Castration-Resistant ; drug therapy ; pathology ; Taxoids ; therapeutic use

Abiraterone Acetate/therapeutic use* ; Androstenes/therapeutic use* ; Dexamethasone/therapeutic use* ; Humans ; Male ; Prostatic Neoplasms, Castration-Resistant/pathology*

Prostate cancer is one of the most common malignancies threatening men's health, and the mechanisms underlying its initiation and progression are poorly understood. Last decade has witnessed encouraging progress in the studies of prostate cancer stem cells (PCSCs), which are considered to play important roles in tumor initiation, recurrence and metastasis, castration resistance, and drug resistance. Therefore, a deeper insight into PCSCs is of great significance for the successful management of prostate cancer. This article presents an overview on the location, origin, and markers of PCSCs as well as their potential correlation with tumor metastasis and castration resistance.
Disease Progression ; Humans ; Male ; Neoplasm Recurrence, Local ; Neoplastic Stem Cells ; pathology ; Prostatic Neoplasms ; etiology ; pathology ; Prostatic Neoplasms, Castration-Resistant ; etiology ; pathology

Prostate cancer (PCa) is the most common cause of malignancy in males and the third leading cause of cancer mortality in the United States. The standard care for primary PCa with local invasive disease mainly is surgery and radiation. For patients with distant metastases, androgen deprivation therapy (ADT) is a gold standard. Regardless of a favorable outcome of ADT, patients inevitably relapse to an end-stage castration-resistant prostate cancer (CRPC) leading to mortality. Therefore, revealing the mechanism and identifying cellular components driving aggressive PCa is critical for prognosis and therapeutic intervention. Cancer stem cell (CSC) phenotypes characterized as poor differentiation, cancer initiation with self-renewal capabilities, and therapeutic resistance are proposed to contribute to the onset of CRPC. In this review, we discuss the role of CSC in CRPC with the evidence of CSC phenotypes and the possible underlying mechanisms.
Androgen Antagonists/therapeutic use* ; Cell Differentiation/genetics* ; Disease Progression ; Humans ; Male ; Neoplastic Stem Cells/pathology* ; Prostatic Neoplasms/pathology* ; Prostatic Neoplasms, Castration-Resistant/pathology* ; Signal Transduction/genetics*

ObjectiveTo explore the expression of I-5α-reductase (SRD5A1)and its prognostic role in prostate cancer .

METHODSData about SRD5A1 were retrieved from the ONCOMINE database and the role of SRD5A1 in prostate cancer was analyzed.

RESULTSTotally, 992 studies of different types relevant to the expression of SRD5A1 were identified in the ONCOMINE database. The SRD5A1 expression was statistically significant in 239 of the studies, overexpressed in 157 (11 in prostate cancer) and underexpressed in the other 82 (3 in prostate cancer). Eighteen of the studies, with 1 068 samples, addressed the expression of SRD5A1 in prostate cancer and normal tissues, which was significantly higher in the former than in the latter tissue (P<0.05). In 3 of the studies, the SRD5A1 expression was high in primary prostate cancer and increased with its metastasis (P<0.0 5). Two of the studies with prognostic data showed a higher rate of postoperative biochemical recurrence and a higher total mortality rate in the patients with a high than in those with a low expression of SRD5A1 (P<0.05).

CONCLUSIONSSRD5A1 is highly expressed in prostate cancer, especially in metastatic and castration-resistant prostate cancer and its expression is associated with the prognosis of prostate cancer, which may be an important target of medication for prostate cancer.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase ; metabolism ; Data Mining ; Humans ; Male ; Neoplasm Recurrence, Local ; Prognosis ; Prostatic Neoplasms ; enzymology ; mortality ; pathology ; surgery ; Prostatic Neoplasms, Castration-Resistant ; enzymology

We reviewed and analyzed the clinical data for a patient with metastatic castration-resistant prostate cancer (mCRPC) from September, 2009 to December, 2014. After the treatment with abiraterone, patient's performance status improved, pain relieved, total prostate specific antigen (tPSA) and free prostate specific antigen (fPSA) markedly decreased. tPSA or fPSA fluctuated between 
30 and 50 ng/mL or between 10 and 20 ng/mL. MRI showed the left peripheral zone reduced. MRI and bone single photon emission computed tomography (SPECT) scan showed no new metastasis. These results indicated that application of abiraterone for patient with mCRPC not only decreased prostate specific antigen (PSA) levels and tumor volume, but also blocked bone metastasis progression and enhanced pain relief.
Androstenes ; therapeutic use ; Bone Neoplasms ; drug therapy ; secondary ; Disease Progression ; Humans ; Male ; Prostate-Specific Antigen ; blood ; Prostatic Neoplasms, Castration-Resistant ; drug therapy ; pathology

Ethnicity might be associated with treatment outcomes in advanced prostate cancer. This study aimed to evaluate the efficacy and safety of androgen deprivation therapy (ADT) combined with apalutamide in East Asians with metastatic castration-sensitive prostate cancer (mCSPC). The original phase 3 Targeted Investigational Treatment Analysis of Novel Anti-androgen (TITAN) trial was conducted at 260 sites in 23 countries. This subgroup analysis included patients enrolled in 62 participating centers in China, Japan, and Korea. Radiographic progression-free survival (PFS), time to prostate-specific antigen (PSA) progression, and PSA changes from baseline were compared between groups in the East Asian population. The intent-to-treat East Asian population included 111 and 110 participants in the apalutamide and placebo groups, respectively. The 24-month radiographic PFS rates were 76.1% and 52.3% in the apalutamide and placebo groups, respectively (apalutamide vs placebo: hazard ratio [HR] = 0.506; 95% confidence interval [CI], 0.302-0.849; P = 0.009). Median time to PSA progression was more favorable with apalutamide than placebo (HR = 0.210; 95% CI, 0.124-0.357; P < 0.001). Median maximum percentages of PSA decline from baseline were 99.0% and 73.9% in the apalutamide and placebo groups, respectively. The most common adverse event (AE) was rash in the apalutamide group, with a higher rate than that in the placebo group (37.3% vs 9.1%). The most common grade 3 or 4 AEs were rash (12 [10.9%]) and hypertension (12 [10.9%]) for apalutamide. The efficacy and safety of apalutamide in the East Asian subgroup of the TITAN trial are consistent with the global results.
Androgen Antagonists/adverse effects* ; Exanthema/chemically induced* ; Far East ; Humans ; Male ; Prostate-Specific Antigen ; Prostatic Neoplasms, Castration-Resistant/pathology* ; Thiohydantoins/adverse effects*