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*

PURPOSE: Metastatic prostatic adenocarcinoma can be controlled by androgen ablation through the active process of programmed cell death in androgen responsive cells. However, about 20-30% of patients have no clinical response to androgen withdrawal. Because of the importance of apoptosis in effecting tumor control, factors involved in this process may be helpful in predicting androgen insensitivity. So, we evaluated the significance of bcl-2 protooncogene expression pattern with therapeutic response of prostatic cancer MATERIALS AND METHODS: We examined the cellular expression of bel-2 protein using immunohistochemical stain in tumor samples from 40 patients with metastatic prostatic cancer(stage D) and determined whether expression of blc-2 protein has related to the therapeutic response of prostatic cancer. RESULTS: The hormonal status of the patient's tumor was determined by the clinical response to therapy. Androgen independent cancer was defined as that subset of patients who experienced no initial response to androgen ablation, or who experienced disease relapse following an initial response to androgen ablation. So, we found that androgen dependent prostatic cancer was 22 patients and androgen independent prostatic cancer was 18 patients. The positive staining for bcl-2 was 27.3%(6/22) and 83.3%(15/18) in androgen dependent and independent prostatic cancer, respectively. It was significant difference(p<0.05). CONCLUSIONS: These results suggest that bcl-2 expression is associated with androgen independent prostatic cancer and used one of the factors to predict which patient with prostatic cancer will respond to androgen ablation.
Adenocarcinoma ; Apoptosis ; Cell Death ; Humans ; Prostate* ; Prostatic Neoplasms* ; Prostatic Neoplasms, Castration-Resistant ; Recurrence

This is a case report of 3 patients who had a dramatic and long-term complete response after antiandrogen withdrawal. All 3 patients were diagnosed with advanced or metastatic prostate cancer with a high prostate-specific antigen (PSA) level. For all patients, we started combined androgen blockade as androgen deprivation therapy and the PSA concentration decreased to <0.1 ng/mL, but then started to increase. After discontinuation of antiandrogen the PSA concentration decreased again and has remained below the limit of sensitivity for more than 1 year in all 3 patients.
Androgen Antagonists ; Humans ; Prostate ; Prostate-Specific Antigen ; Prostatic Neoplasms ; Prostatic Neoplasms, Castration-Resistant

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

Androstenes ; Docetaxel ; Humans ; Male ; Prednisone ; Prostatic Neoplasms ; Prostatic Neoplasms, Castration-Resistant

Prostate cancer generally relapses into castration resistant prostate cancer (CRPC) after androgen deprivation therapy, which may be associated with androgen metabolism, particularly de novo androgen synthesis apart from the amplification and mutation of androgen receptor and the activation of its signaling pathways. This article focuses on the advances in the studies of the changes in androgen metabolism and de novo androgen synthesis in CRPC as well as their possible mechanisms and clinical significance.
Androgen Antagonists ; pharmacology ; Androgens ; biosynthesis ; metabolism ; Humans ; Male ; Orchiectomy ; Prostate ; metabolism ; Prostatic Neoplasms, Castration-Resistant ; metabolism

Authors raised that staging based strategies and practice of integrative medicine (IM) by combining syndrome typing and disease identification, and choosing suitable measures in accordance with different persons and seasonal conditions after more than ten years' clinical practice and researches. Radical operation as prior (as evil eliminating) and strengthening vital qi in perioerative period are best strategy for promoting rapid rehabilitation of early stage prostate cancer patients. Strengthening body resistance to eliminate evil was used in treating advanced prostate cancer patients. For example, a comprehensive treatment program for hormone-dependent patients was combined with endocrinotherapy and Chinese herbs for synergisic efficacy-enhancing actions. In this way, these patients' quality of life (QOL) were improved and time to castration resistant prostate cancer (CRPC) was delayed, even some patients were clinically cured. There are lack of effective medicines and methods for CRPC patients. Greatly tonifying original qi is mainly used for improving their clinical symptoms and prolonging survivals. Practice has proved staging based strategies and practice of IM has favorable advantages in treating prostate cancer, especially showing prospect in prolonging survival and postponing progression of advanced prostate cancer patients. Besides, it also could provide beneficial considerations and inspiration for combination of syndrome typing and disease identification.
Disease Progression ; Humans ; Male ; Medicine, Chinese Traditional ; Neoplasm Staging ; Prostatic Neoplasms, Castration-Resistant ; diagnosis ; Quality of Life

OBJECTIVETo introduce the framework of evidence-based practice with a case of castration-resistant prostate cancer (CRPC) as an example.

METHODSA clinical question was formulated according the clinical scenario. A systematic search was conducted for the published literature in the databases of PubMed, EMBASE, Cochrane Library, Clinical Trial Registries, and Web of Knowledge up to Dec 2014. The identified literature was reviewed for quality appraisal before the evidence was applied to clinical practice.

RESULTSThe treatment was effective and the patient achieved disease remission.

CONCLUSIONEvidence-based practice should be integrated with clinical scenario, current evidence, and patients' willingness, and follow a systematic framework.

Non-coding RNAs (ncRNAs) are a large class of RNA molecules that do not encode proteins, regulate gene expressions multifacetedly, and influence the metabolism, proliferation, differentiation and apoptosis of cells as well as the occurrence and progression of tumors. Some of the ncRNAs act as cancer genes, such as miR-19a, miR-125b, miR-616, miR-7, miR-221, MALAT-1, and PRNCR1, which are upregulated in castration-resistant prostate cancer (CRPC) tissues or cell lines, and promote the development and progression of CRPC, some act as tumor suppressor genes, including miR-185, miR-342, miR-15, miR-16, and miR-146, which are downregulated in CRPC tissues or cell lines and inhibit or delay the occurrence of CRPC, and still others, such as miR-7, miR-19a, miR-125b, miR-221, and MALAT-1, are differentially expressed in the serum or tissue and can be used as potential biomarkers for the early diagnosis and prognosis of CRPC. This article presents an overview on the roles of ncRNAs in the occurrence, progression, diagnosis, and prognosis of CRPC and advances in their studies.
Humans ; Male ; MicroRNAs ; genetics ; Prostatic Neoplasms, Castration-Resistant ; genetics ; RNA, Untranslated ; genetics

Reprogramming of metabolism is a hallmark of tumors, which has been explored for therapeutic purposes. Prostate cancer (PCa), particularly advanced and therapy-resistant PCa, displays unique metabolic properties. Targeting metabolic vulnerabilities in PCa may benefit patients who have exhausted currently available treatment options and improve clinical outcomes. Among the many nutrients, glutamine has been shown to play a central role in the metabolic reprogramming of advanced PCa. In addition to amino acid metabolism, glutamine is also widely involved in the synthesis of other macromolecules and biomasses. Targeting glutamine metabolic network by maximally inhibiting glutamine utilization in tumor cells may significantly add to treatment options for many patients. This review summarizes the metabolic landscape of PCa, with a particular focus on recent studies of how glutamine metabolism alterations affect therapeutic resistance and disease progression of PCa, and suggests novel therapeutic strategies.
Male ; Humans ; Glutamine/therapeutic use* ; Prostatic Neoplasms, Castration-Resistant/drug therapy*