前列腺摘除术与去势术前后雄激素变化的研究

目的探讨和研究前列腺摘除术与去势术对血清中雄激素(T、FT、DHT)的变化。方法39例研究对象,其中23例前列腺摘除术,16例去势术在手术前后分别采集血清样本,用放射免疫法测定血清中T、FT、DHT浓度。结果 前列腺摘除术后血清中T、FT、DHT分别较术前下降34.45％,33.53％,50.41％;去势术后血清中T、FT、DHT分别较术前下降92.27％,92.26％,58.36％。两种手术前后血清中T、FT、DHT的变化都有显著的统计学意义(P<0.001)。结论 前列腺摘除术后血清中雄激素会发生明显的变化,以DHT改变为显著。而去势术能够去除绝大部分T、FT,而DHT仅下降58.36%,在雄激素依赖的前列腺癌病例应当继续使用雄激素受体竞争剂,阻止残存的雄激素作用。     

前列腺癌经去势术加中药治疗后PSA和性激素变化的意义

目的：探讨外科去势术加中药为主的综合疗法治疗前列腺癌(PCa)转变为雄激素非依赖型PCa的出现时间、机制以及可采取的延缓其出现的措施。方法：对27例晚期PCa患者在行双侧睾丸切除术后行10％鸦胆子油乳等治疗，并动态检测前列腺特异抗原(PSA)和性激素水平，观察临床表现的变化。结果：PSA由治疗前89．8μg／L降至治疗后第4周的2．63μg／L，且维持至2．5年以内，睾酮由治疗后第2周降至正常值以下，一直维持至3年，而卵泡刺激素、黄体生成素持续在正常值水平以上。余性激素雌二醇、黄体酮、催乳素等均在正常范围内波动。当PSA正常时，临床表现明显好转；而当PSA倍增出现时，临床病情恶化。结论：外科去势术加中药鸦胆子油乳等治疗中、晚期PCa可在2．5年后开始转变为雄激素非依赖型PCa，且有延缓其发生和出现的意义。     

前列腺癌患者去势术后的睾酮水平

目的 探讨进展期前列腺癌患者去势术后平均睾酮水平，以指导内分泌治疗。方法 进展期前列腺癌患者40例，去势术后，未用任何抗雄激素药物，分别于术前、术后1周及1、3、6、9、12个月，观察血清总睾酮和PSA变化。结果 去势术后6个月，40例患者血清睾酮平均水平〈1．9nmol／L（95％可信区间1．2～1．9nmol／L）；13例患者睾酮〉1．9nmol／L，平均Gleason评分为6．8分。术后6个月，36例患者PSA〈1ng／ml，平均Gleason评分为6．3分；4例患者PSA〉1ng／ml，平均Glcason评分为8．0分。结论 前列腺癌患者去势术后，平均血清睾酮水平〈1．9nmol／L，部分患者需继续抗雄激素药物治疗。术后PSA逐渐下降，6个月降至最低值。     

药物去势和手术去势对前列腺癌患者性激素的影响

目的比较药物去势与手术去势对前列腺癌患者血清性激素水平的影响。方法对40例行手术去势、22例药物去势(黄体生成素释放激素类似物,LHRH-A;每4周皮下注射1次)的前列腺癌患者治疗前及治疗后1、3个月血清睾酮(T)、雌二醇(E2)、孕激素(P)、卵泡刺激素(FSH)、黄体生成素(LH)、泌乳素(PRL)水平进行检测,统计学分析比较2组患者去势后性激素变化情况。结果手术去势组治疗前及治疗后1、3个月T为(19.3±10.6)、(1.1±0.8)、(0.9±0.7)nmol/L,E2为(104.3±58.4)、(53.4±36.9)、(50.7±37.5)pmol/L,P为(2.6±1.6)、(1.8±1.3)、(1.7±1.4)nmol/L,FSH为(10.8±6.5)、(73.8±31.4)、(75.1±28.7)IU/L,LH为(11.2±7.5)、(38.3±20.6)、(37.4±30.5)IU/L,PRL为(14.5±8.9)、(12.8±7.6)、(13.2±7.9)μg/L;药物去势组治疗前及治疗后1、3个月T为(21.1±11.7)、(1.2±0.7)、(1.0±0.6)nmol/L,E2为(110.5±62.7)、(36.5±30.4)、(34.7±28.6)pmol/L,P为(2.7±1.4)、(0.8±0.6)、(0.7±0.6)nmol/L,FSH为(11.2±7.0)、(5.5±4.3)、(5.8±4.0)IU/L,LH为(12.0±6.7)、(0.8±0.4)、(0.7±0.4)IU/L,PRL为(15.2±7.6)、(13.8±8.2)、(14.2±9.4)μg/L。2组治疗1个月后,T值均显著下降。药物去势治疗后FSH、LH明显下降,而手术去势后FSH、LH明显上升。药物去势组治疗后E2、P下降程度大于手术去势组。结论药物去势与手术去势对前列腺癌患者的性激素水平可产生不同影响。     

LHRH-A治疗前列腺癌去势后复发转移疗效的探讨(附5例报告)

作者报告自1994年以来,用LHRH-A治疗前列腺癌做去势术后复发或转移的病人,其中2例为用过缓退瘤(Flutamide)和1例为用过Estramustine控制一时期后复发的病人。5例皆有效,其中4例已控制2年以上。这一事实提示LHRH-A不只是具有“药物去势”作用;去势后促使前列腺癌细胞生长的雄性激素来自肾上腺和其他组织;雄性激素作用于前列腺癌细胞的受体;长期使用LHRH-A起到选择性“药物切除垂体”,达到全雄性激素阻断的作用。建议对LHRH-A在人类前列腺癌治疗作用机制,应作进一步的前瞻性研究。     

去势抵抗性前列腺癌治疗进展

大部分前列腺癌经过治疗终将进展为临床难治的去势抵抗性前列腺癌,目前的治疗手段均难以提高其2~3年的生存期。近年来通过不同作用机制治疗去势抵抗性前列腺癌的许多新型有效的药物投入临床或进入临床试验。本文就这方面的研究进展作一综述。     

前列腺癌内分泌治疗后进展为去势抵抗性前列腺癌的危险因素研究进展

内分泌治疗是进展期前列腺癌(PCa)的主要治疗方法之一。然而,大部分患者在1~3年内分泌治疗后将逐渐进展为去势抵抗性前列腺癌(CRPC)。CRPC目前仍是不可治愈的,而且预后不良。因此,研究PCa内分泌治疗后进展为CRPC的危险因素,可为PCa的治疗及促进康复提供一定的理论依据。本文综合国内外现有研究报道,对PCa内分泌治疗后进展为CRPC的相关危险因素进行综述。     

手术去势治疗药物去势抵抗性前列腺癌的临床研究

<正>药物去势是晚期转移性前列腺癌的一线治疗方案,但是经过中位18~24个月后,几乎所有患者病变都将复发及进展演变为药物去势抵抗性前列腺癌(medical castration resistant prostate cancer,CRPC),对于此类病变,患者中位生存20个月[1-2]。目前标准CRPC治疗方案为多西他赛/泼尼松方案化疗,但化疗不良反应较大,加上给药期间患者生活质量明显降低,许多患者不能耐受或拒绝化疗[3],因此,     

前列腺癌患者手术去势与药物去势的去势效果及相关不良反应比较的真实世界研究

目的:通过回顾性分析总结真实世界中手术去势与药物去势对前列腺癌患者的去势效果以及相关不良反应的影响,从而为前列腺癌患者内分泌治疗的选择提供现实指导。方法:收集2014年1月—2019年1月在川北医学院附属医院行手术去势(130例)和药物去势(114例)的前列腺癌患者资料,包括患者治疗前体重指数(body mass index, BMI)、空腹血糖(fasting blood glucose, FBG)、甘油三酯(triglyceride, TG)、血清总胆固醇(serum total cholesterol, TC)、尿酸(uric acid, UA)、高密度脂蛋白(high-density lipoprotein, HDL)、低密度脂蛋白(low-density lipoprotein, LDL)、前列腺特异性抗原(prostate specific antigen, PSA)、睾酮(testosterone, T)及Gleason评分等检验指标,并使用国际前列腺症状评分(IPSS)以及前列腺癌患者生活质量子量表(QLQ-PR25)进行相关评分,以手术日或第1次注射促黄体生成激素释放...     

去势抵抗性前列腺癌的治疗新进展

随着人们生活方式的改变以及前列腺特异性抗原筛查的普及,前列腺癌的诊断和治疗更为重要。尽管内分泌治疗对于进展性前列腺癌有治疗效果,但最终会进展为去势抵抗性前列腺癌,从而严重影响患者的生存期。近年来,研究者对于去势抵抗性前列腺癌的治疗做出了巨大努力,包括新的内分泌治疗、细胞毒性的化学治疗、免疫治疗以及以骨转移为靶点的治疗方式逐步问世,本文就这些新的治疗进展进行综述,以期为临床医生及进展性前列腺癌患者提供更多的治疗选择,延长总体生存期,提高生活质量。     

Androgen Deprivation Therapies and Changes in Comorbidity: A Comparison of Gonadotropin-releasing Hormone Agonists and Antiandrogen Monotherapy as Primary Therapy in Men with High-risk Prostate Cancer

Background

Some studies suggest that gonadotropin-releasing hormone (GnRH) agonists are associated with higher risk of adverse events than antiandrogens (AAs) monotherapy. However, it has been unclear whether this is due to indication bias.

Androgen Deprivation Therapy and Overall Survival for Gleason 8 Versus Gleason 9–10 Prostate Cancer

Background

While the addition of androgen deprivation therapy (ADT) to external beam radiation therapy (EBRT) is known to improve overall survival (OS) in Gleason 8–10 (Grade Group 4–5) prostate cancer (PCa), it has been hypothesized that Gleason 9–10 disease, which is less differentiated than Gleason 8 disease, may be less sensitive to ADT.

Effect on Survival of Androgen Deprivation Therapy Alone Compared to Androgen Deprivation Therapy Combined with Concurrent Radiation Therapy to the Prostate in Patients with Primary Bone Metastatic Prostate Cancer in a Prospective Randomised Clinical Trial: Data from the HORRAD Trial

Background

The cornerstone of standard treatment for patients with primary bone metastatic prostate cancer (mPCa) is androgen deprivation therapy (ADT). Retrospective studies suggest a survival benefit for treatment of the primary prostatic tumour in mPCa, but to date, no randomised-controlled-trials (RCTs) have been published addressing this issue.

Testosterone Measurement in Patients with Prostate Cancer

Context

Serum testosterone measurement has no widely accepted place in the management of patients with prostate cancer (PCa). However, several potential clinical applications of serum testosterone determination can be envisaged.

Objective

To review the role of testosterone and the androgen axis in the natural history of PCa and evaluate the evidence for the clinical application of serum testosterone measurement in patient screening, diagnosis, and management.

Evidence acquisition

A Medline search retrieved original research and review articles relating to the androgen axis in PCa and the use of testosterone measurement for (1) assessing PCa risk in the general population, (2) adding to the specificity of prostate-specific antigen (PSA) testing, (3) determining tumour aggressiveness, (4) assessing the efficacy of androgen-deprivation therapy (ADT), and (5) optimising the scheduling of intermittent ADT. Relevant data were reviewed during a roundtable discussion, and consensus recommendations were agreed.

Evidence synthesis

A body of data implicates the androgen axis in PCa throughout its natural history. Based on current evidence, serum testosterone measurement cannot be recommended for determining PCa risk, increasing specificity of PSA testing, or assessing tumour aggressiveness. In contrast, for patients receiving ADT, there is a clear rationale for serum testosterone monitoring to ensure that castration levels are achieved. Practical recommendations for testosterone measurement during ADT are outlined. If PSA is rising while on ADT, castration levels of serum testosterone must be demonstrated before hormonal independence can be assumed. Serum testosterone levels might be considered an additional trigger for therapy reinitiation in intermittent ADT schedules. Finally, future prospective studies should further evaluate the potential relevance of testosterone measurement as an independent assessment of prognosis and treatment decision in different disease stages.

Conclusions

As a therapeutic target, serum testosterone levels should be monitored to verify response to ADT and confirm suspected castration independence.     

Degarelix as an Intermittent Androgen Deprivation Therapy for One or More Treatment Cycles in Patients with Prostate Cancer

Background

Guidelines for prostate cancer treatment suggest that intermittent androgen deprivation (IAD) can be considered for certain patients.

Objective

To evaluate the efficacy and safety of degarelix as IAD for one or more treatment cycle(s) in prostate cancer patients requiring androgen deprivation.

Design, setting, and participants

This open-label uncontrolled multicenter study included patients with prostate-specific antigen (PSA) >4 to 50 ng/ml or PSA doubling time <24 mo. Induction included 7-mo treatment. Off-treatment period started when PSA was ≤4 ng/ml and lasted up to 24 mo based on PSA and testosterone levels. Treatment was reinitiated when PSA was >4 ng/ml.

Intervention

Each induction period included a starting dose of degarelix 240 mg, and thereafter 80 mg once a month for 6 mo, followed by off-treatment periods.

Outcome measurements and statistical analysis

The primary end point was time to PSA >4 ng/ml. Secondary end points were subgroup analysis of the primary end point, time to testosterone >0.5 and >2.2 ng/ml, quality of life (QoL), and sexual function during the first off-treatment period.

Results and limitations

Of 213 patients in the first induction period, 191 entered the first off-treatment period, 35 patients entered the second induction, and 30 entered the second off-treatment period. Only two patients entered the third cycle. Median time to PSA >4 ng/ml and duration of first off-treatment period was 392 d each. Significant differences in time to PSA >4 ng/ml were observed between subgroups stratified by prognostic factors (previous curative treatment, cancer stage, PSA levels, and Gleason scores). Time to testosterone >0.5 and >2.2 ng/ml was 112 and 168 d, respectively. Change in QoL remained nonsignificant, and sexual function gradually improved during the off-treatment period. Adverse events were fewer during the off-treatment period and subsequent treatment cycles.

Conclusions

IAD with degarelix resulted in an improvement in sexual function commensurate with increased testosterone levels while PSA remained suppressed. The treatment for one treatment cycle or more was well tolerated.

Patient summary

Guidelines for prostate cancer treatment suggest that intermittent androgen deprivation (IAD) can be considered for certain patients. IAD with degarelix resulted in improved sexual function commensurate with increased testosterone levels while prostate-specific antigen remained suppressed. The treatment for one treatment cycle or more was well tolerated.

Trial registration

Clinicaltrials.gov identifier NCT00801242.     

Use of Concomitant Androgen Deprivation Therapy in Patients Treated with Early Salvage Radiotherapy for Biochemical Recurrence After Radical Prostatectomy: Long-term Results from a Large,Multi-institutional Series

Background

Hormonal manipulation concomitant to salvage radiotherapy (SRT) given for biochemical recurrence (BCR) after radical prostatectomy (RP) improved outcomes in two randomized trials. However, neither of these studies focused on men treated at low prostate-specific antigen (PSA) levels.

Gonadotropin-releasing Hormone Agonists and Acute Kidney Injury in Patients with Prostate Cancer

Background

Androgen deprivation therapy (ADT) might increase the risk of acute kidney injury (AKI) in patients with prostate cancer (PCa).

Objective

To examine the impact of ADT on AKI in a large contemporary cohort of patients with nonmetastatic PCa representing the US population.

Design, setting, and participants

Overall, 69 292 patients diagnosed with nonmetastatic PCa between 1995 and 2009 were abstracted from the Surveillance Epidemiology and End Results–Medicare database.

Outcomes measurements and statistical analyses

Patient in both treatment arms (ADT vs no ADT) were matched using propensity-score methodology. Ten-year AKI rates were estimated. Competing-risks regression analyses tested the association between ADT and AKI, after adjusting for the risk of death during follow-up.

Results and limitations

Overall, the 10-yr AKI rates were 24.9% versus 30.7% for ADT-naive patients versus those treated with ADT, respectively (p < 0.001). When patients were stratified according to the type of ADT, the 10-yr AKI rates were 31.1% versus 26.0% for men treated with gonadotropin-releasing hormone (GnRH) agonists and bilateral orchiectomy, respectively (p < 0.001). In multivariable analyses, the administration of GnRH agonists (hazard ratio [HR]: 1.24; 95% confidence interval [CI], 1.18–1.31; p < 0.001), but not bilateral orchiectomy (HR: 1.11; 95% CI, 0.96–1.29; p = 0.1), was associated with the risk of experiencing AKI. Our study is limited by its retrospective design.

Conclusions

ADT is associated with an increased risk of AKI in patients with nonmetastatic PCa. In particular, the administration of GnRH agonists, but not surgical castration, may substantially increase the risk of experiencing AKI. These observations should help provide physicians with better patient selection to reduce the risk of AKI.

Patient summary

The administration of gonadotropin-releasing hormone agonists, but not bilateral orchiectomy, increases the risk of acute kidney injury (AKI) in patients with prostate cancer (PCa). These observations should help provide physicians with better patient selection to reduce the risk of AKI in PCa patients.     

去势治疗对前列腺癌患者骨密度的影响

目的 :探讨去势治疗对前列腺癌患者骨密度 (BMD)的影响。　方法 :4 9例完成BMD测定的前列腺癌患者分为 2组 :非去势组 2 1例 ,在去势治疗前即已完成BMD测定 ;去势组 2 8例 ,均为去势治疗 1年以上者。BMD测定采用双能X线吸收法 (DEXA法 ) ,测定部位为腰椎 (L2～ 4)和股骨颈。为校正年龄、性别和体重因素对BMD的影响 ,与年龄、种族等相配对的Z评分被用于结果评估。　结果 :13例 (6 2 % )非去势组患者和 2 3例 (82 % )去势组患者均存在不同程度的BMD水平下降。在非去势组 ,腰椎 (L2～ 4)Z评分为 - (0 .9± 0 .7)分 ,股骨颈Z评分为 - (0 .6± 0 .5 )分 ;而在去势组 ,腰椎 (L2～ 4)Z评分为 - (1.8± 1.1)分 ,股骨颈Z评分为 - (1.6± 1.0 )分。与非去势组相比 ,去势组患者BMD水平明显偏低 ,差异有显著性 (P <0 .0 1)。　结论 :去势治疗前 ,前列腺癌患者常伴有不同程度的骨量减少和骨质疏松 ,去势治疗与前列腺癌患者BMD水平下降明显相关。在对前列腺癌患者采用去势治疗之前 ,BMD测定是必要的。     

Potential Benefits of Intermittent Androgen Suppression Therapy in the Treatment of Prostate Cancer: A Systematic Review of the Literature

Context

The well-known side-effect profile of androgen-deprivation therapy (ADT) has significant quality-of-life (QoL) implications. Intermittent androgen deprivation (IAD) alternates androgen blockade with treatment cessation to allow hormonal recovery between treatment cycles, thus potentially improving tolerability and QoL.

Objective

To evaluate available evidence regarding the efficacy and tolerability of IAD and assess its value in the treatment of prostate cancer (PCa).

Evidence acquisition

Key phase 2/3 clinical trials of IAD in PCa published within the last 10 yr were identified on Medline using the terms prostatic neoplasms [MeSH], intermittent androgen suppression, intermittent hormonal deprivation, intermittent androgen deprivation, and intermittent hormonal therapy. Abstracts from trials reported at 2008–2009 conferences were also included.

Evidence synthesis

Data from 19 phase 2 studies are discussed with respect to prostate-specific antigen values for treatment suspension/reinitiation, treatment regimens, cycle lengths, testosterone normalisation, and tolerability. Outcome data were promising: Most trials reported an improvement in QoL during the off-therapy periods. Interim data from eight phase 3 trials comparing IAD and continuous androgen deprivation (CAD) support the phase 2 results. IAD generally showed comparable efficacy to CAD with respect to various outcomes, including biochemical progression, progression-free survival, and overall survival. However, IAD was significantly better than CAD with respect to 3-yr risk of progression in one study, and it demonstrated tolerability benefits, particularly with respect to sexual function. Patients most likely to benefit from IAD and factors predictive of poor response are also discussed.

Conclusions

IAD seems to be as effective as CAD while showing tolerability and QoL advantages, especially recovery of sexual potency; however, there are as yet insufficient data to determine whether IAD has the potential to prevent or reverse the long-term complications associated with ADT.