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*

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.

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*

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*

Most prostate cancer cases ultimately relapse after a period of initial response to castration therapy and progress to intractable castration-resistant prostate cancer (CRPC). Hardly any therapeutic options currently used can improve the 2- to 3-year survival of the patient. Recently, some new drugs for the treatment of CRPC through various action mechanisms have been approved, and others are in the advanced stage of clinical trial. This review provides an overview of these new therapeutic agents.
Antineoplastic Agents ; therapeutic use ; Humans ; Male ; Neoplasm Recurrence, Local ; Orchiectomy ; Prostatic Neoplasms ; surgery ; Prostatic Neoplasms, Castration-Resistant ; drug therapy ; mortality

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

The diagnosis and treatment of prostate cancer are being improved due to the popularized screening of prostate specific antigen. Advanced prostate cancer, in spite of its response to androgen deprivation therapy, may finally develop into castration-resistant prostate cancer (CRPC) and shorten the overall survival of the patients. Many efforts have been made by worldwide researchers for new approaches to the management of CRPC, including new hormonal therapy, cytotoxic chemotherapy, immunotherapy, and bone metastasis-targeted therapy. This paper reviews the emerging agents undergoing clinical evaluation and drugs that have received approval for the treatment of CRPC in order to provide doctors and patients with more treatment options for CRPC and improve the overall survival rate and quality of life of the patients.
Androgen Antagonists ; Bone Neoplasms ; prevention & control ; Humans ; Immunotherapy ; Male ; Prostate-Specific Antigen ; blood ; Prostatic Neoplasms, Castration-Resistant ; therapy ; Quality of Life

Management and treatment of terminal metastatic castration-resistant prostate cancer (mCRPC) remains heavily debated. We sought to investigate the efficacy of programmed cell death 1 (PD-1) inhibitor plus anlotinib as a potential solution for terminal mCRPC and further evaluate the association of genomic characteristics with efficacy outcomes. We conducted a retrospective real-world study of 25 mCRPC patients who received PD-1 inhibitor plus anlotinib after the progression to standard treatments. The clinical information was extracted from the electronic medical records and 22 patients had targeted circulating tumor DNA (ctDNA) next-generation sequencing. Statistical analysis showed that 6 (24.0%) patients experienced prostate-specific antigen (PSA) response and 11 (44.0%) patients experienced PSA reduction. The relationship between ctDNA findings and outcomes was also analyzed. DNA-damage repair (DDR) pathways and homologous recombination repair (HRR) pathway defects indicated a comparatively longer PSA-progression-free survival (PSA-PFS; 2.5 months vs 1.2 months, P = 0.027; 3.3 months vs 1.2 months, P = 0.017; respectively). This study introduces the PD-1 inhibitor plus anlotinib as a late-line therapeutic strategy for terminal mCRPC. PD-1 inhibitor plus anlotinib may be a new treatment choice for terminal mCRPC patients with DDR or HRR pathway defects and requires further investigation.
Male ; Humans ; Prostate-Specific Antigen ; Treatment Outcome ; Prostatic Neoplasms, Castration-Resistant/drug therapy* ; Immune Checkpoint Inhibitors/therapeutic use* ; Retrospective Studies

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

Bipolar androgen therapy (BAT), as a new therapeutic strategy for castration-resistant prostate cancer (CRPC), can significantly reduce the level of prostate-specific antigen (PSA) for prostate cancer patients and has exhibited an excellent safety profile with no serious adverse events. Based on the clinical trials recently published at home and abroad, this article reviews the background, action mechanism, development, and prospect of BAT.
Androgen Antagonists ; therapeutic use ; Hormone Replacement Therapy ; methods ; Humans ; Male ; Prostate-Specific Antigen ; blood ; Prostatic Neoplasms, Castration-Resistant ; blood ; drug therapy ; Receptors, Androgen ; Testosterone ; administration & dosage ; blood