Vaccine therapy for prostate cancer

Immunotherapy with vaccines represents a novel, targeted nontoxic modality for the therapy of prostate cancer. Systemic immune responses to candidate prostate cancer antigens have been induced in a tumor that has been conventionally viewed as refractory to immunotherapy. Autologous dendritic cell vaccines expressing prostate-specific antigens have shown promising clinical outcomes in a randomized trial in metastatic androgen independent prostate cancer. Other vaccine approaches include granulocyte-macrophage colony-stimulating factor modified tumor cell vaccines and poxvirus vaccines. A combination of vaccines with chemotherapy, radiotherapy, and other biologic agents is also being evaluated. Efforts to optimize vaccine approaches and select ideal patient populations need to continue because there is no evidence supporting a single superior approach.     

Indication for nuclear medicine therapy in advanced cancer of the prostate

Summary For patients with advanced prostate cancer efficient therapy of painfull bony lesions is the primary goal of interdisciplinary treatment strategies. Preservation of quality of life appears to be the main aim rather than prolongation of life. Apart from oral pain relief and local irradiation systemic treatment with radionuclides offers low-risk radiotherapeutic strategies for the palliation of painful, multifocal osteoplastic bone metastases. Depending on the radiopharmaceutical substance chosen response and reduction of pain are described in 65–80 %. The duration of pain relief lasts between 6–12 weeks. During this time the morphine based medication can be reduced and in some cases withdrawn which positively effects quality of life. After improvement of myelosuppression treatment with radionuclides can be repeated. Patients have to be hospitalized for two days because of protection from radiation procedures.      

Advances in specific immunotherapy for prostate cancer

OBJECTIVES: The absence of effective therapies for advanced prostate cancer has entailed an intensive search for novel treatments. This review presents an overview of specific immunotherapeutic strategies for prostate cancer. METHODS: Current literature was reviewed regarding the identification of tumor antigens and the design of T-cell- and antibody-based immunotherapy for prostate cancer. The PubMed database was searched using the key words antibodies, clinical trials, dendritic cells, immunotherapy, prostate cancer, and T cells. RESULTS: T cells and antibodies are powerful components of the specific antitumor immune response. CD8+ cytotoxic T lymphocytes (CTLs) efficiently destroy tumor cells. CD4+ T cells improve the antigen-presenting capacity of dendritic cells (DCs) and support the stimulation of tumor-reactive CTLs. Monoclonal antibodies exhibit their antitumor effects via antibody-dependent cellular cytotoxicity and complement activation. Consequently, much attention has been given to the identification of tumor antigens that represent attractive targets for specific immunotherapy. Several prostate cancer-related antigens were described and used in clinical trials. Such studies were based on the administration of peptides, proteins, or DNA. Furthermore, men with prostate cancer were vaccinated with peptide-, protein-, or RNA-loaded DCs, which display an extraordinary capacity to induce tumor-reactive T cells. Monoclonal antibodies directed against surface antigens were also used. Clinical trials revealed that immunotherapeutic strategies represent safe and feasible concepts for the induction of immunologic and clinical responses in men with prostate cancer. CONCLUSIONS: Specific immunotherapy represents a promising treatment modality for prostate cancer. Further improvement of the current approaches is required and may be achieved by combining T-cell- and antibody-based vaccination strategies with radio-, hormone-, chemo-, or antiangiogenic therapy.     

Genetic predisposition to prostate cancer: Update and future perspectives

ObjectiveProstate cancer is the second most frequent cancer in men worldwide and kills over 250,000 men worldwide every year. Prostate cancer is a heterogeneous disease at the clinical and the molecular level. The Scandinavian Twin Registry Study demonstrated that in contrast to most malignancies where environment was the overriding influence, heritable factors account for more than fifty percent of prostate cancers.Methods and materialsWe review the literature on prostate cancer risk variants (rare and common) including SNPs and Copy Number Variants (CNVs) and discuss the potential implications of significant variants for prostate cancer patient care.ResultsThe search for prostate cancer susceptibility genes has included both family-based studies and case-control studies utilizing a variety of approaches from array-based to sequencing-based studies. A major challenge is to identify genetic variants associated with more aggressive, potentially lethal prostate cancer and to understand their role in the progression of the disease.ConclusionFuture risk models useful in the clinical setting will likely incorporate several risk loci rather than single variants and may be dependent on an individual patient’s ethnic background.     

Androgen and prostate cancer: the role of primary androgen deprivation therapy in localized prostate cancer

BackgroundThe basic mechanisms and clinical efficacy of primary androgen deprivation therapy (PADT), especially combined androgen blockade (CAB) for localized or locally advanced prostate cancer (PCa) have been outlined. An important point relates to which patients are suitable candidates for PADT.MethodsA retrospective review of the efficacy of PADT in 628 patients with localized or locally advanced PCa treated with PADT at seven institutions in Japan was carried out.ResultsIt was found that more than 30% of low- or intermediate-risk localized PCa patients could have their disease controlled over the long-term by PADT alone. Short-term or intermittent PADT could not be recommended because of the possibility of character change in the cancer cells as a result of incomplete androgen ablation.ConclusionAlgorithms are proposed for the treatment of localized PCa not only in low- and intermediate-risk groups, but also in the high-risk group. Future research directions are indicated.     

晚期前列腺癌患者行间歇性内分泌治疗的疗效分析

目的探讨间歇性内分泌治疗在晚期前列腺癌患者中的疗效,并分析影响疗效的相关因素。方法2004年9月到2012年7月间收治晚期前列腺癌患者首先进行6-9个月的内分泌治疗,然后进行疗效评估,将对内分泌治疗敏感的患者随机分为间歇治疗组和持续治疗组,观察两组的疗效、毒副作用及患者的生活质量评分等指标,并分析间歇治疗组中影响患者预后的相关因素。结果共收治174例晚期前列腺癌患者,有130例患者对内分泌治疗敏感,其中58例患者接受间歇性内分泌治疗,72例患者接受持续性内分泌治疗。间歇治疗组患者的生活质量KPS评分明显高于持续治疗组（80vs70,P〈0．05）,相关并发症发生率也低于持续治疗组。但两组患者的5年内发展成为非激素依赖性前列腺癌的比例（37％vs41％）及患者的5年生存率（72％vs63％）无明显差异。Cox多因素分析显示晚期前列腺癌患者的Gleason评分及第一次治疗后PSA水平与患者的预后密切相关,可作为判断能否行间歇性内分泌治疗及预后的重要指标。结论对于晚期前列腺癌患者行间歇性内分泌治疗安全可行、疗效确切,对患者的生活质量影响小,同时也可减少患者的经济压力。     

Contemporary role of androgen deprivation therapy for prostate cancer

Context

Androgen deprivation therapy (ADT) for prostate cancer (PCa) represents one of the most effective systemic palliative treatments known for solid tumors. Although clinical trials have assessed the role of ADT in patients with metastatic and advanced locoregional disease, the risk-benefit ratio, especially in earlier stages, remains poorly defined. Given the mounting evidence for potentially life-threatening adverse effects with short- and long-term ADT, it is important to redefine the role of ADT for this disease.

Objective

Review the published experience with currently available ADT approaches in various contemporary clinical settings of PCa and reported serious treatment-related adverse events. This review addresses the level of evidence associated with the use of ADT in PCa, focusing upon survival outcome measures. Furthermore, this paper discusses evolving approaches targeting androgen receptor signaling pathways and emerging evidence from clinical trials with newer compounds.

Evidence acquisition

A comprehensive review of the literature was performed, focusing on data from the last 10 yr (January 2000 to July 2011) and using the terms androgen deprivation, hormone treatment, prostate cancer and adverse effects. Abstracts from trials reported at international conferences held in 2010 and 2011 were also evaluated.

Evidence synthesis

Data from randomized controlled trials and population-based studies were analyzed in different clinical paradigms. Specifically, the role of ADT was evaluated in patients with nonmetastatic disease as the primary and sole treatment, in combination with radiation therapy (RT) or after surgery, and in patients with metastatic disease. The data suggest that in men with nonmetastatic disease, the use of primary ADT as monotherapy has not shown a benefit and is not recommended, while ADT combined with conventional-dose RT (<72 Gy) for patients with high-risk disease may delay progression and prolong survival. The postoperative use of ADT remains poorly evaluated in prospective studies. Likewise, there are no trials evaluating the role of ADT in patients with biochemical relapses after surgery or RT. In patients with metastatic disease, there is a clear benefit in terms of quality of life, reduction of disease-associated morbidity, and possibly survival. Treatment with bilateral orchiectomy, luteinizing hormone-releasing hormone agonist therapy, with and without antiandrogens has been associated with various serious adverse events, including cardiovascular disease, diabetes, and skeletal complications that may also affect mortality.

Conclusions

Although ADT is an effective treatment of PCa, consistent long-term benefits in terms of quality and quantity of life are predominantly evident in patients with advanced/metastatic disease or when ADT is used in combination with RT (<72 Gy) in patients with high-risk tumors. Implementation of ADT should be evidence based, with special consideration to adverse events and the risk-benefit ratio.     

Hormonal therapy and chemotherapy in hormone-naive and castration resistant prostate cancer

The management of advanced castration resistant prostate cancer (CRPC) has been rapidly changing and is still evolving. In the last years, there has been an increasing knowledge of prostate cancer biology. New therapeutic agents and approaches have been evaluated demonstrating benefits in survival and quality of life in patients with metastatic prostate cancer.     

The effects of prostate cancer on intimate relationships

Prostate cancer (PCA) represents an intensely ‘personal’ medical condition. PCA and its treatments affect intimate aspects of a man's bodily and psychological function, aspects that only the man himself and his partner can fully appreciate. There is growing evidence that the diagnosis of PCA has important adverse psychosocial effects on both the patient and his partner. An understanding of the ways in which a patient's female partner is affected by PCA is beginning to emerge. In this review several key issues for future psychosocial research are outlined and discussed: adjusting to the challenge of the PCA diagnosis, the impact on the couples’ relationship, the dilemma of treatment choice, the desire to conceal treatment side-effects, the effect of gender on the reaction of patients and female partners, and the unique problems facing same-sex couples. Pulling these issues together, the conclusion is drawn that psychosocial interventions designed to help the couple face this ‘relationship disease’ together are the most likely to be acceptable and effective for those affected by this common cancer.     

放射性粒子组织间植入治疗局限性前列腺癌

目的：探讨放射性粒子组织间植入治疗局限性前列腺癌的安全性和有效性。方法：采用实时直肠超声引导经会阴穿刺放射性^125I粒子组织间植入治疗T1～T2c期前列腺癌患者45例。结果：45例患者手术均顺利完成,手术时间60～120（平均90）min,植入^125I粒子数40～75（平均56）枚。术后随访12～48个月,血PSA〈1μg／L29例,血PSA为1～2μg／L 11例,血PSA≥2μg／L5例。结论：放射性粒子组织间植入治疗局限性前列腺癌安全有效。     

缓退瘤治疗晚期前列腺癌(附10例报道)

目的：探讨缓退瘤治疗晚期前列腺癌的效果。方法：行去势手术加口服缓退瘤治疗晚期前列腺癌１０例。结果：生存８例,死亡２例。生存者转移灶消失,原发灶缩小。结论：对晚期前列腺癌行去势术加缓退瘤的治疗效果较好。     

前列腺体积和前列腺特异抗原密度与前列腺穿刺阳性率的关系

目的:探讨前列腺体积及前列腺特异抗原密度与前列腺穿刺阳性率的关系并分析其原因.方法:选择2004～2007年间于我院行超声引导下经直肠前列腺系统8针穿刺的患者192例.以前列腺体积<30 ml、30～50 ml、>50 ml为界,计算并比较各组问前列腺穿刺的阳性率及PSAD≥0.15时,前列腺穿刺阳性率的变化.结果:前列腺体积与前列腺穿刺阳性率呈负相关(r＝0.237,P<0.01),前列腺体积<30 ml组,穿刺阳性率为39.1%(18/46);30～50 ml组,阳性率为21.7%(13/60);>50 ml组,阳性率为9.3%(8/86).各组间差异有统计学意义(P<0.01,P<0.05).前列腺特异抗原密度≥0.15时,三组间阳性率差异仍有统计学意义(P<0.01).但三组漏诊率分别为11.1%(2/18)、30.8%(4/13)、62.5%(5/8),差异有统计学意义(P<0.01).结论:前列腺体积是前列腺穿刺阳性率的独立影响因素,应根据前列腺体积制定穿刺方案.     

Screening for prostate cancer

Carcinoma of the prostate gland is the secondmost common cancer among men with anage-adjusted incidence of 635 cases per 100,000men aged 65 and older. While there are severalproven methods for detecting prostate cancer,debate continues as to the best way to detectit early as well as who should receiveparticular screening. There are differingopinions as to proven benefit even when canceris detected. Fortunately, newer methodscontinue to be developed that will hopefullyreduce false positive detection rates whileinsuring an adequate level of screeningprotection.     

Nomograms are key decision-making tools in prostate cancer radiation therapy

Background

The use of nomograms for predicting clinical endpoints has been well documented. Nomograms provide an individualized prognosis and help clinicians determine the effectiveness of treatment for a given patient. Early identification of potential treatment failure or toxicity allows alternative approaches to be considered, reducing unnecessary treatment, morbidity, and cost. This review aims to evaluate clinical potential of nomogram use for the management of prostate cancer radiotherapy patients.

Molecular markers of prostate cancer

Although prostate-specific antigen (PSA) has evolved as a very useful tool for detection of prostate cancer, there remains an urgent need for more accurate biomarkers to diagnose prostate cancer and predict cancer-related outcomes. Recent advances in the study of proteomics and high throughput techniques have led to the discovery of many potential biomarkers for prostate cancer. This article briefly reviews the current status of PSA testing and discusses several candidate protein biomarkers for prostate cancer, as well as highlighting some recent proteomic discoveries with the potential to supplement or even replace PSA for the diagnosis and prognosis of prostate cancer.     

Adjuvant therapy in lymphnode positive prostate cancer

Summary Few patients with prostate cancer metastatic to the lymphnodes can be cured by radiotherapy, radical prostataectomy or androgen deprivation. Inevitably serum PSA levels will rise after a few years whereas the clinical recurrence appears after 5 to 10 years. Prospective trials regarding adjuvant treatment of lymphnode positive prostate cancer do not exist. Retrospective studies involving adjuvant endocrine treatment reveal a prolonged disease free survival time. Scientific proof of the best treatment for prostate cancer with lymphnode metastasis does not exist. The decision how to treat is based on our personal experience and philosophy as well as on our knowledge and interpretation of the available lierature. The art of medicine is the feeling for the best treatment of each individual patient.      

International variation in prostate cancer incidence and mortality rates

Context

Wide variation exists internationally for prostate cancer (PCa) rates due to differences in detection practices, treatment, and lifestyle and genetic factors.

Objective

We present contemporary variations in PCa incidence and mortality patterns across five continents using the most recent data from the International Agency for Research on Cancer.

Evidence acquisition

PCa incidence and mortality estimates for 2008 from GLOBOCAN are presented. We also examine recent trends in PCa incidence rates for 40 countries and mortality rates for 53 countries from 1985 and onward via join-point analyses using an augmented version of Cancer Incidence in Five Continents and the World Health Organization mortality database.

Evidence synthesis

Estimated PCa incidence rates remain most elevated in the highest resource counties worldwide including North America, Oceania, and western and northern Europe. Mortality rates tend to be higher in less developed regions of the world including parts of South America, the Caribbean, and sub-Saharan Africa. Increasing PCa incidence rates during the most recent decade were observed in 32 of the 40 countries examined, whereas trends tended to stabilize in 8 countries. In contrast, PCa mortality rates decreased in 27 of the 53 countries under study, whereas rates increased in 16 and remained stable in 10 countries.

Conclusions

PCa incidence rates increased in nearly all countries considered in this analysis except in a few high-income countries. In contrast, the increase in PCa mortality rates mainly occurred in lower resource settings, with declines largely confined to high-resource countries.     

Cardiovascular risk with androgen deprivation therapy for prostate cancer: Potential mechanisms

Androgen deprivation therapy (ADT) is frequently used for the treatment of advanced prostate cancer. ADT is associated with numerous side effects related to its mode of action, namely the suppression of testosterone to castrate levels. Recently, several large retrospective studies have also reported an increased risk of diabetes and cardiovascular disease in men receiving ADT, although these risks have not been confirmed by prospective randomized trials. We review the literature to consider the risk of cardiovascular disease with different forms of ADT and examine in detail potential mechanisms by which any such risk could be mediated. Mechanisms discussed include the metabolic syndrome resulting from low testosterone level and the potential roles of testosterone flare, gonadotropin-releasing hormone receptors outside the pituitary gland, and altered levels of follicle-stimulating hormone. Finally, the clinical implications for men prescribed ADT for the treatment of advanced prostate cancer are considered.