前列腺癌的内分泌治疗

前列腺癌是男性泌尿生殖系统肿瘤中极为重要的一种，本文概述了新近前列癌的内分泌治疗的有关原理，基础研究及临床应用现状。     

晚期转移性前列腺癌内分泌治疗分析

目的 探寻晚期转移性前列腺癌内分泌治疗效果及生存预后的预测因子. 方法 1996年12月至2008年3月收治前列腺癌患者820例,其中晚期转移性前列腺癌患者364例,均接受内分泌治疗并且具有完整临床病理资料.364例患者,末次随访时间2008年3月31日,中位随访时间24(3～135)个月.患者随访期间进展为雄激素非依赖性前列腺癌250例.对364例患者的内分泌治疗效果及生存预后进行分析.生存函数分析运用Kaplan-Meier法,单因素和多因素分析运用Cox回归,采用Log-rank法进行显著性检验. 结果 364例患者内分泌治疗有效率98%(357/364),中位无进展生存时间20(1～113)个月,1、2、3年无进展生存率分别为69%、39%、27%.多因素分析结果 显示:基线PSA>20 nglml(HR 2.279,95%CI 1.239～4.190)、临床分期(HR 6.879,95%CI 2.480～19.083)、内分泌治疗过程中PSA最低值≥1 ng/ml(HR 6.838,95%CI 4.263～10.967)和达到PSA最低值时间≤5个月(HR 0.366,95%CI 0.236～0.570)为晚期转移性前列腺癌内分泌治疗无进展生存时间的不良预后因素. 结论 基线PSA、临床分期、内分泌治疗过程中PSA最低值和达到PSA最低值时间为晚期转移性前列腺癌内分泌治疗无进展生存时间的独立预后因素.     

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。     

前列腺癌内分泌治疗的副作用

前列腺癌的内分泌治疗可以采用不同的方法，这些方法都会产生副作用，它们以不同的方式影响患者的健康和生活质量。本文就内分泌治疗的主要副作用，发病机理和可能的避免方法及治疗作一综述。     

间歇性内分泌治疗前列腺癌

前列腺癌是欧美国家男性最常见的恶性肿瘤,也是全球男性继肺癌之后第二位的恶性肿瘤.随着人口老龄化及诊断水平的提高,我国前列腺癌总体发病率也有增高的趋势,另外,也有发病年龄年轻化及更早期发现的趋势.对于已失去根治机会的晚期前列腺癌,内分泌治疗已成为首选治疗方式.间歇性内分泌治疗(intermittent hormone thempy,IHT)因其有可能提高生活质量、延长雄激素抵抗及存活时间,在近十多年得到广泛关注.     

老年晚期前列腺癌的超低温冷冻联合辅助内分泌治疗

目的:探讨超低温冷冻(CSAP)联合术前新辅助内分泌治疗(NHT)及术后辅助内分泌治疗(AHT),对老年局部晚期前列腺癌患者治疗的安全性和有效性。方法:对65岁以上的29例确诊为局部晚期(T3,T4N0M0)前列腺癌患者,术前3个月行NHT,然后在CT定位下行经会阴前列腺穿刺,应用氩氦超导刀冷冻前列腺组织,术后行AHT。观察综合治疗开始后3周、3个月、1年血清PSA值及前列腺容积的变化、生化复发及临床分期变化的情况。结果:29例围手术期的主要并发症为尿道絮状物脱落梗阻、盆腔痛、尿失禁。治疗后1年血清PSA平均值降至(0.2±0.7)μg/L,前列腺平均容积降至(28±10.97)ml。生化复发4例,临床分期恶化2例。结论:CSAP联合术前NHT及术后AHT的综合治疗老年局部晚期前列腺癌,是一种可选择的安全、有效的方法。     

前列腺癌内分泌治疗的合理选择

自从1941年首次报道以来，前列腺癌的内分泌治疗即在临床上得到广泛应用。经过长期的观察和研究，目前其适用范围已不仅仅局限于对晚期患者的缓解治疗，还包括对早期患者根治术前的新辅助治疗、术后的辅助治疗以及对治愈性治疗后生化复发患者的治疗等。内分泌治疗本身并无治愈效果，甚至其能否延长患者寿命也没有定论，因此对前列腺癌患者选择内分泌治疗时，必须权衡不同治疗方式的利弊，以及对患者生活质量可能造成的影响，方可作出合理决策。     

前列腺癌的内分泌治疗现状及研究进展

目的:前列腺癌发病的流行病学上的改变,导致前列腺癌内分泌治疗的治疗指征和治疗时机也随之改变。本文综述了在新的前列腺癌流行病学背景下,前列腺癌内分泌治疗的现状;同时对内分泌治疗中现存的争议,诸如单纯去势治疗与雄激素联合阻断治疗、间断性雄激素阻断治疗与持续性雄激素阻断治疗、早期内分泌治疗与推迟内分泌治疗等方面的相关研究进展进行了讨论。     

PSA谷值对预测前列腺癌内分泌治疗预后的意义

为了评估前列腺癌内分泌治疗后的PsA谷值是否可预测肿瘤已发展为非激素依赖性。作者回顾性分析了177例经过内分泌治疗的c期或D期前列腺癌患者的进展状况和生存率，运用多因素回归分析方法对PsA谷值与生存率、非激素依赖性前列腺癌的发生率及其进展时间进行了分析。中位随访时间为39个月(3—89个月)，85．4％的患者(151     

前列腺癌内分泌治疗的几个热点问题

1941年Huggins和Hodges首先报道了去势和注射雌激素在转移性前列腺癌患者中的益处。随后的研究证实前列腺癌细胞广泛表达雄激素受体,且依赖于雄激素而生长,从而确立了内分泌治疗的生物学基础。目前内分泌治疗的手段包括手术去势和药物治疗,国内广泛使用的药物是促黄体激素释放激素激动剂(LHRHa)和非甾体类抗雄药。内分泌治疗是晚期前列腺癌的主要治疗方式,如何提高疗效、减少副作用并最终治愈疾病成为近年来的研究热点。本文就几个热点问题进行探讨。一、最大雄激素阻断(maxi mumandrogen blockage,MAB)去势治疗和抗雄药物的联合构成了M…     

射频消融联合内分泌治疗对中晚期前列腺癌治疗价值的初步研究

目的 探讨前列腺射频消融联合内分泌治疗对中晚期前列腺癌的治疗价值.方法 8例确诊中晚期前列腺癌患者在内分泌治疗的基础上联合经直肠超声造影引导及监测下射频消融治疗,使前列腺整体原位灭活.比较观察治疗前后超声改变和血PSA水平变化.结果 所有8例患者行射频消融术后基本达到前列腺整体消融效果,平均消融范围约96%;急性尿潴留症状均得到明显缓解;随访中,2例患者死于心肺功能衰竭(生存时间4个月和12个月),存活6例患者随访中位时间24个月(16~42个月);射频消融术后3个月内所有患者前列腺体积较术前缩小,血PSA水平均较术前下降,差异均有统计学意义(P值均为0.012),其中3例患者PSA水平降到正常范围以内;射频消融治疗1年后复查血P3A水平,3例仍在正常范围以内,3例较前升高.结论 前列腺射频消融联合内分泌治疗有望成为中晚期前列腺癌一种安全有效的综合治疗方案.     

Optimal treatment of locally advanced prostate cancer

The treatment of clinically locally advanced prostate cancer (cT3–4) is subject to controversies. Patients with lymph node metastases as well as patients with overstaged localized and thus curable disease fall into this category. Radical prostatectomy, external beam radiotherapy and early or deferred hormonal therapy are possible treatment options. Multimodal treatment (i.e., a combination of these options) is frequently used. After radical prostatectomy, Gleason score-adjusted disease-specific survival does not differ meaningfully between the tumor stages pT2 and pT3–4. In the case of lymph node metastases after radical prostatectomy, but not in node-negative disease, adjuvant hormonal treatment seems to improve survival. Adjuvant radiotherapy may improve biochemical and local control in locally advanced prostate cancer, a survival benefit has, however, not yet been proven. External beam radiotherapy alone provides unfavourable survival rates in locally advanced prostate cancer. Adjuvant hormonal treatment may improve outcome in this setting. When no curative treatment is chosen, early hormonal treatment seems to provide modest benefit compared with deferred therapy.     

Cardiovascular mortality and duration of androgen deprivation for locally advanced prostate cancer: analysis of RTOG 92-02

OBJECTIVES: Gonadotropin-releasing hormone agonists (GnRHa) are associated with greater risk of coronary heart disease and myocardial infarction in men with prostate cancer, but little is known about their potential effects on cardiovascular mortality. We assessed the relationship between duration of GnRHa therapy and cardiovascular mortality in a large randomized trial of men treated with short-term versus longer-term adjuvant goserelin and radiation therapy (RT) for locally advanced prostate cancer. METHODS: From 1992 to 1995, 1554 men with locally advanced prostate cancer (T2c-4, prostate-specific antigen [PSA] <150ng/ml) received RT and 4 mo of goserelin and then were randomized to no additional therapy (arm 1) or 24 mo adjuvant goserelin (arm 2) in a phase 3 trial (Radiation Therapy Oncology Group [RTOG] 92-02). Cox regression analyses were performed to evaluate the relationship between treatment arm and cardiovascular mortality. Covariates included age, prevalent cardiovascular disease (CVD), hypertension, diabetes (DM), race, PSA, Gleason score, and stage. RESULTS: After median follow-up of 8.1 yr, 185 cardiovascular-related deaths had occurred. No increase in cardiovascular mortality occurred for men receiving a longer duration of goserelin. At 5 yr, cardiovascular mortality for men receiving longer-term adjuvant goserelin was 5.9% versus 4.8% with short-term goserelin (Gray's p=0.16). In multivariate analyses, treatment arm was not significantly associated with increased risk of cardiovascular mortality (adjusted hazard ratio [HR]=1.09; 95% confidence interval [CI], 0.81-1.47; p=0.58; when censoring at time of salvage goserelin, HR=1.02, 95%CI, 0.73-1.43; p=0.9). Traditional cardiac risk factors, including age, prevalent CVD, and DM, were significantly associated with greater cardiovascular mortality. CONCLUSIONS: Longer duration of adjuvant GnRHa therapy does not appear to increase cardiovascular mortality in men with locally advanced prostate cancer.     

Androgen deprivation therapy for the treatment of prostate cancer: consider both benefits and risks

Context

Androgen deprivation therapy (ADT) is increasingly used for the treatment of prostate cancer (PCa), even in clinical settings in which there is no evidence-based proof of prolonged overall survival (OS). ADT, however, may be associated with numerous side effects, including an increased therapy-related cardiovascular mortality.

Objective

To discuss different clinical settings in which ADT is currently used and to critically weigh the benefits of ADT against its possible side effects.

Evidence acquisition

A MEDLINE search was conducted to identify original articles and review articles addressing the efficacy and side effects of ADT for the treatment of PCa. Keywords consisted of prostate cancer, hormonal therapy, adverse effects, radical prostatectomy, and radiotherapy. The articles with the highest level of evidence for the various examined end points were identified with the consensus of all authors and were reviewed.

Evidence synthesis

Even short-term use of ADT may lead to numerous side effects, such as osteoporosis, obesity, sarcopenia, lipid alterations, insulin resistance, and increased risk for diabetes and cardiovascular morbidity. Despite these side effects, ADT is commonly used in various clinical settings in which a clear effect on improved OS has not been shown.

Conclusions

ADT is associated with an increased risk of multiple side effects that may reduce quality of life and/or OS. Consequently, these issues should be discussed in detail with patients and their families before initiation of ADT. ADT should be used with knowledge of its potential long-term side effects and with possible lifestyle interventions, especially in settings with the highest risk–benefit ratio, to alleviate comorbidities.     

The prognostic importance of prostate specific antigen in the monitorisation of patients undergoing maximum androgen blockade for metastatic prostate cancer

Introduction The changes in serum prostate specific antigen (PSA) concentrations can be used as a prognostic factor in patients undergoing maximum androgen blockade for metastatic prostate cancer. Material and method A total of 149 patients followed up in our department were classified into 4 groups on the basis of PSA changes: group 1; those with normalisation of PSA levels within the first 3 months, group 2; those with normalisation PSA between months 3 and 6, group 3; those with a decrease in PSA but not reaching normal range, group 4; those with no decrease. The gleason scores and the number of bone metastases were also compared between the groups. Result The time to progression was significantly delayed in group 1 (mean: 23.3 months) compared to those with group 2 (mean: 16.9 months) (P < 0.02). The time to progression in group 3 (mean: 8.45 months) was significantly shorter compared to the first two groups (P < 0.001). Also, in patients with gleason scores 5–7 (grades 2) and gleason scores over 7 (grade 3) and group 1, the time to progression (mean: 21.2 months) was significantly delayed compared to those with the same gleason scores but with group 2 (mean: 13.4 months) (P < 0.001). Conclusion The decrease in PSA level is more important than gleason scores in determining the time to progression. Early normalisation of PSA delays the time to progression, and when combined with gleason scores, PSA is an important prognostic factor in predicting the success of the therapy.     

Secondary hormonal therapy for advanced prostate cancer

PURPOSE: Androgen ablation remains the cornerstone of management for advanced prostate cancer. Therapeutic options in patients with progressive disease following androgen deprivation include antiandrogen withdrawal, secondary hormonal agents and chemotherapy. Multiple secondary hormonal agents have clinical activity and the sequential use of these agents may lead to prolonged periods of clinical response. We provide a state-of-the-art review of the various agents currently used for secondary hormonal manipulation and discusses their role in the systemic treatment of patients with prostate cancer. MATERIALS AND METHODS: A comprehensive review of the peer reviewed literature was performed on the topic of secondary hormonal therapies, including oral antiandrogens, adrenal androgen inhibitors, corticosteroids, estrogenic compounds, gonadotropin-releasing hormone antagonists and alternative hormonal therapies for advanced prostate cancer. RESULTS: Secondary hormonal therapies can provide a safe and effective treatment option in patients with AIPC. The use of steroids and adrenolytics, such as ketoconazole and aminoglutethimide, has resulted in symptomatic improvement and a greater than 50% prostate specific antigen decrease in a substantial percent of patients with AIPC. A similar clinical benefit has been demonstrated with estrogen based therapies. Furthermore, these therapies have demonstrated a decrease in metastatic disease burden. Other novel hormonal therapies are currently under investigation and they may also show promise as secondary hormonal therapies. Finally, guidelines from the United States Food and Drug Administration Prostate Cancer Endpoints Workshop were reviewed in the context of developing new agents. CONCLUSIONS: Secondary hormonal therapy serves as an excellent therapeutic option in patients with AIPC in whom primary hormonal therapy has failed. Practicing urologists should familiarize themselves with these oral medications, their indications and their potential side effects.     

Plasma osteocalcin values and related hormonal parameters in patients subjected to a variety of prostate anticancer agents

Summary Circulating osteocalcin (OC) and cortisol levels were measured in blood samples from 93 patients with dissaminated prostate cancer. Among these subjects 79 had not responsed to therapy, while 14 had responded to a variety of anticancer treatment strategies (orchiectomy, cyproterone acetate (CPA), flutamide, Buserelin, diethylstilbestrol (DES), Estracyt, and polyestradiol phosphate). The control group consisted of 19 patients with benign prostatic hypertrophy. In the majority of these patients blood adrenocorticotropic hormone (ACTH), estradiol human growth hormone (hGH), and thyroid stimulating hormone (TSH) levels were also assessed. In nonresponders to therapy with DES and Estracyt subnormal circulating OC levels were measured, while normal OC values were found in nonresponders to other treatment strategies. In patient given Estracyt highly elevated estradiol levels were recorded. Subnormal and/or low-normal estradiol concentrations were found in patients subjected to CPA and DES. Elevated blood cortisol levels were assessed in subjects treated with DES and Estracyt while at the same time either subnormal and low-normal plasma ACTH concentrations were measured in these same patients. Accordingly, the decline observed in OC concentration seems to be a consequence of the well-established inhibitory effect of glucorticoids on osteoblast activity. The decline in blood cortisol levels obtained after administration of dexamethasone in patients given DES and Estracyt may be attributed both to possible changes in catabolic pathways and to the contribution of the negative neuroendocrinological feedback.