即刻辅助内分泌治疗在高危局限期或局部晚期前列腺癌根治性手术后的应用价值

目的:以术后2年PSA复发率评价高危局限期或局部晚期前列腺癌根治性手术后即刻辅助内分泌治疗(AHT)的疗效。方法:回顾性总结在2010年9月至2012年3月在我院泌尿外科确诊为高危局限期或者局部晚期的62例前列腺癌患者。所有患者在术前(腹腔镜或耻骨后前列腺癌根治术)均行MRI、ECT(全身骨显像检查),均未发现有区域盆腔淋巴结及骨转移。其中32例患者(A组)在手术后2周至1个月内给予辅助内分泌治疗(AHT),包括口服及注射药物;30例患者(B组)术后未采取任何处理措施。所有患者在术后每3个月复查1次PSA,每6个月行1次ECT检查,每3个月随访1次(包括患者的药物不良反应、用药持续时间及剂量、生存质量),共计2年。结果:A组中有7例患者生化复发,其2年的总体无生化复发率为78.13%。B组中有14例生化复发,其2年的总体无生化复发率为53.33%(P0.05)。结论:高危局限期或局部晚期前列腺癌根治性手术后即刻AHT可以提高患者无生化复发生存率,对控制该疾病的进一步发展甚至术后的转移有重要意义。     

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。     

Early hormonal data from a multicentre phase II trial using transdermal oestrogen patches as first-line hormonal therapy in patients with locally advanced or metastatic prostate cancer

OBJECTIVE

To assess the hormonal effects of Fem7® (Merck, KGaA, Darmstadt, Germany) 100 µg transdermal oestrogen patches on men undergoing first‐line androgen‐deprivation therapy for prostate cancer.

PATIENTS AND METHODS

PATCH is a multicentre, randomized, phase II trial for men with locally advanced or metastatic prostate cancer, comparing luteinizing hormone‐releasing hormone agonist therapy with oestrogen patches. To assess the dosing schedule for the patches, as this was the first time that this brand of patch had been used in men, and to reassure patients and participating clinicians, the Independent Data Monitoring Committee agreed to early release of hormonal data from this study.

RESULTS

Oestradiol, testosterone and prostate‐specific antigen (PSA) levels are presented for the first group of 14 patients who received the patches (with 1 withdrawal) and for whom there were ≥12 weeks of follow‐up by March 2007. After 12 weeks, testosterone levels (nmol/L) in eight of the 13 patients were <1.7, two were 1.7–2 and three were >2. The median (range) serum oestradiol levels was 442 (52.1–1542) pmol/L and all patients had a PSA response, with eight having a PSA level of <4 ng/mL.

CONCLUSION

These results confirm that oestrogen patches produce castrate levels of testosterone and concomitant PSA responses. They also highlighted the potential differences between different brands of oestrogen patches, and the need to monitor hormonal response, toxicity and efficacy until more experience with oestrogen patches for this clinical indication is obtained. The number of patches recommended in the PATCH study has now been increased.     

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.     

Efficacy of primary hormonal therapy for patients with localized and locally advanced prostate cancer: A retrospective multicenter study

AIM: A retrospective review of patients with localized and locally advanced prostate cancer was performed to evaluate the efficacy of primary hormonal therapy and predict long-term prognosis in these patients. METHODS: A total of 628 patients who were diagnosed with stage T1c to T3 prostate cancer were treated with primary hormonal therapy at participating institutions. The patients were classified based on pretreatment prostate-specific antigen (PSA) level, Gleason score, and time to nadir PSA level. Disease-specific and progression-free survival rates were investigated, and compared among the subgroups. RESULTS: The mean age of patients was 74.5 years, and median pretreatment PSA level was 14.0 ng/mL. A total of 399 patients (63.5%) were treated with combined androgen blockade (CAB), and 229 patients (36.5%) were treated with castration monotherapy. The disease-specific survival rate of all 628 patients was 89.1% at 8 years. The group that showed a good response to primary hormonal therapy (Group G, pretreatment PSA level < or =20 ng/mL, Gleason score < or =7, and time to nadir PSA < or =6 months) accounted for approximately one-third of the total number of T1c-T3 patients. Disease-specific and progression-free survival rates at 8 years in Group G were 98.9% and 82.0%, respectively. These rates increased to 100% and 87.3%, respectively, in patients receiving CAB treatment in Group G. CONCLUSIONS: The results indicate the usefulness of primary hormonal therapy, especially CAB treatment, for patients showing a good response to hormonal therapy in long-term control of localized and locally advanced prostate cancer.     

Hormone therapy for locally advanced prostate cancer

PURPOSE: We assessed cause specific and all cause survival in men with locally advanced prostate cancer after hormone therapy. MATERIALS AND METHODS: Between February 1991 and November 2000, 208 men with locally advanced prostate cancer were treated with gonadal androgen ablation or gonadal androgen ablation and an antiandrogen at a single medical center. Median PSA was 46 ng./ml. (range 2 to 748). Median potential followup was 78 months (range 4 to 122) and the median observation period was 46 months (range 3 to 122). RESULTS: Of the patients 14 (7%) died of causes related to cancer and 71 (34%) died of competing co-morbid disease. Actuarial cause specific survival at 5 and 8 years was 92% and 80%, respectively. The only demographic or tumor related variable that influenced cause specific survival was Gleason score less than 8 versus 8 or greater (p = 0.02). Actuarial all cause survival at 5 and 8 years was 59% and 41%, respectively. The only variable that influenced all cause survival was a Charlson weighted co-morbidity score of less than 2 versus 2 or greater (p <0.0001). Major morbidity from the primary tumor, including bothersome obstructive voiding symptoms requiring transurethral prostate resection, ureteral obstruction or persistent hematuria, developed in 13 patients (6%), while major treatment related morbidity, including flutamide hepatotoxicity and hip fracture, developed in 4. CONCLUSIONS: Hormone therapy for locally advanced prostate cancer is associated with minimal morbidity from the primary tumor and from treatment. All cause survival parallels that reported for integrated hormone and radiation therapy.     

Bicalutamide as immediate therapy either alone or as adjuvant to standard care of patients with localized or locally advanced prostate cancer: first analysis of the early prostate cancer program

PURPOSE: We determine the efficacy and tolerability of bicalutamide as immediate therapy, either alone or as adjuvant to treatment of curative intent, in patients with clinically localized or locally advanced prostate cancer. MATERIALS AND METHODS: This international program consists of 3 ongoing, randomized, double-blind, placebo controlled clinical trials (trials 23, 24, and 25). Men with localized or locally advanced (T1-T4, Nx/N0, M0) prostate cancer were randomized to receive 150 mg. bicalutamide daily or placebo, in addition to standard care with radical prostatectomy, radiotherapy or watchful waiting. Primary end points are time to objective progression and overall survival. In this first analysis data from the trials were combined in a single overview analysis according to protocol. RESULTS: Data are available for 8,113 patients (4,052 randomized to bicalutamide, 4,061 to standard care alone) at a median followup of 3.0 years. Treatment with bicalutamide provided a highly significant reduction of 42% in the risk of objective progression compared with standard care alone (9.0% versus 13.8%, hazards ratio 0.58; 95% confidence interval 0.51, 0.66; p <0.0001). The overall result was reflected in 2 of the 3 trials (trials 24 and 25) with trial 3 (trial 23) showing a nonsignificant difference at this time. Reductions in the risk of disease progression were seen across the entire patient population, irrespective of primary treatment or disease stage. Overall survival data are currently immature and longer followup will determine if there is also a survival benefit with bicalutamide. The most frequently reported side effects of bicalutamide were gynecomastia and breast pain. CONCLUSIONS: Immediate treatment with 150 mg. bicalutamide daily, either alone or as adjuvant to treatment of curative intent, significantly reduces the risk of disease progression in patients with localized or locally advanced prostate cancer. This benefit must be balanced with the morbidity associated with long-term hormonal therapy. Followup is ongoing to determine potential survival benefits of this treatment approach.     

新辅助治疗的优势:机器人辅助腹腔镜下前列腺癌根治术治疗局部进展期前列腺癌

目的探讨术前新辅助内分泌治疗(NHT)是否能使接受机器人辅助腹腔镜前列腺癌根治术(RLRP)治疗的局部进展期前列腺癌患者临床获益。方法回顾性研究中国医科大学附属第一医院泌尿外科自2018年5月至2019年8月根治术前通过穿刺活检及MRI诊断为局部进展期前列腺癌患者31例。其中术前行新辅助内分泌治疗12例,年龄(65.67±5.123)岁,未经内分泌治疗19例,年龄(66.58±8.520)岁。比较两组患者手术时间、术中出血量、术后住院时间、术后切缘阳性率、淋巴结阳性率、术后吻合口漏尿等情况。结果 31例手术均无中转开放及二次手术。新辅助治疗组手术时间[(176.84±54.875)min vs.(66.58±8.520)min,P=0.032]和术后住院时间[(9.50±2.505)min vs.(13.87±5.987)min,P=0.048]缩短,术中失血量[(165.68±79.746)mL vs.(13.87±5.987)mL,P=0.013]减少。治疗组肿瘤切缘阳性率(8.33%vs.26.32%,P=0.001)和清扫淋巴结阳性率(17.14%vs.38.18%,P=0.037)也明显低于对照组。术前辅助内分泌治疗并不能降低术后Gleason评分和临床分期(P>0.05)。结论术前新辅助内分泌治疗在RLRP治疗局部进展期前列腺癌患者中可能在一定程度上降低手术难度并且减少术中出血,使患者受益。     

Radiation therapy in the management of locally advanced prostate cancer

Locally advanced prostate cancer generally refers to those patients with clinical stages T3-4 disease. Patients with locally advanced cancer frequently are included in clinical trials that examine treatment for patients at high risk for relapse based on presenting prostate-specific antigen, high Gleason score, or advanced clinical stage. There is a growing body of evidence that suggests that men with localized prostate cancer benefit from high-dose radiation therapy delivered with three-dimensional conformal radiation therapy, intensity-modulated radiation therapy, or proton beam therapy. Most importantly, neoadjuvant and adjuvant androgen-deprivation therapy have significantly improved outcomes in men with locally advanced or high-risk prostate cancer. Although questions remain regarding the optimal timing and duration of adjuvant hormonal therapy, a combination of long-term androgen deprivation started before radiation therapy and continued for 2 years represents a North American standard of care for this patient population.     

氩氦刀冷冻术联合间歇性内分泌治疗治疗局部晚期前列腺癌的初步研究

目的探讨氩氦刀冷冻术(argon-helium cryoablation,AHC)联合间歇性内分泌治疗(intermittent hormonal therapy,IHT)治疗局部晚期前列腺癌(locally advanced prostate cancer,LAPC)的疗效和安全性。方法回顾性分析经直肠超声引导下经会阴前列腺穿刺AHC联合IHT治疗的21例LAPC患者的临床资料,并与18例单纯行IHT治疗的LAPC患者进行对照。评估的指标包括血清总前列腺特异性抗原(total prostate specific antigen,tPSA)、最大尿流率(Qmax)、国际前列腺症状评分(IPSS)、前列腺体积、前列腺MRI和全身骨扫描,生活质量调查采用欧洲癌症研究与治疗组织的QLQ-C30总量表和QLQ-PR25子量表,并记录不良反应。结果 AHC治疗患者的tPSA提前达到最低值,Qmax和IPSS评分改善明显,前列腺体积明显缩小,第一轮停用内分泌药物的时间也明显延长;躯体功能和性功能的明显下降以及局部的疼痛,对患者的生活质量造成一定的影响。AHC术后主要并发症为阴囊水肿、盆腔疼痛、闭孔神经炎、尿道腐肉和后尿道狭窄,但未出现尿失禁、尿道直肠瘘等严重并发症。结论 AHC联合IHT治疗LAPC是一种可选择的安全、有效的方法。     

不同时间新辅助内分泌治疗联合调强放疗对局部晚期前列腺癌疗效的影响作用

目的 探讨局部晚期前列腺癌联合治疗中新辅助内分泌治疗( neoadjuvant hormonal therapy,NHT)的理想方案. 方法 诊断明确的局部晚期(T3 - T4N0M0)前列腺癌患者60例,均采用NHT联合调强放疗(intensity modulated radiotherapy,IMRT)的治疗方案,随机分为3组,每组20例.根据放疗前NHT时间不同,分为2周NHT(A组)、3个月NHT(B组)和6个月NHT组(C组).内分泌治疗持续时间为NHT开始至IMRT结束后12个月.NHT结束后检测血清PSA、经直肠超声下前列腺体积和Qmax.放疗结束后每3个月检查上述指标. 结果 3组患者NHT后PSA中位数分别下降至24.88、0.20和0.07 μg/L,与治疗前比较差异有统计学意义(P＜0.05);B、C组前列腺体积明显缩小(P＜0.05),其中B组缩小20.8％,C组缩小39.5％;B组、C组Qmax分别为(11.70±2.81)和( 14.45±2.61)mL/s,与治疗前比较明显增加(P＜0.05).内分泌联合放疗后12个月,3组间PSA比较差异均有统计学意义(P＜0.01),C组＜B组＜A组;B、C组前列腺体积缩小较A组明显(P＜0.01),B组与C组比较差异无统计学意义(P＞0.05);组间Qmax值比较差异有统计学意义(P＜0.01),C组＞B组＞A组. 结论 NHT联合IMRT是治疗局部晚期前列腺癌的理想方法,放疗前NHT治疗时间至少应达到3个月.     

Recent progress in hormonal therapy for advanced prostate cancer

PURPOSE OF REVIEW: Primary androgen deprivation therapy and secondary hormonal therapy remain the cornerstones of treatment for advanced prostate cancer. This review outlines the basic evidence for use of hormonal therapy while highlighting major research developments made in the past year. RECENT FINDINGS: Recent research on androgen deprivation therapy has suggested that patients with high-risk features may have longer metastasis-free survival with early initiation of androgen deprivation therapy. Fracture risk has been shown to be significantly increased in patients on androgen deprivation therapy and is correlated with duration of treatment. In the treatment of androgen-independent prostate cancer, oral premarin has been shown to induce of prostate specific antigen responses more than 50% in 32% of patients, though thromboembolism remains a risk despite prophylactic low-dose warfarin. Transdermal estradiol has been associated with virtually no cardiovascular toxicity, but induced of prostate specific antigen responses more than 50% in only 12.5% of patients. Clinical studies of nilutamide, flutamide, and ketoconazole have further clarified efficacy of these secondary hormonal treatments. SUMMARY: Optimal timing of androgen deprivation therapy awaits the results of randomized trials, but available evidence indicates that patients with high-risk features may benefit from early androgen deprivation therapy. New estrogen-based therapies have shown promising efficacy in the treatment of androgen-independent prostate cancer, with significantly less cardiovascular toxicity than traditional estrogens.     

Primary hormone therapy for locally advanced prostate cancer

Locally advanced prostate cancer is a treatment dilemma. As with prostate cancer in general, there is no clear evidence that aggressive intervention (ie, surgery or radiation) is superior to noninvasive interventions (eg, delayed treatment or androgen ablation). Because patients with locally advanced prostate cancer have a high risk of local and systemic recurrence, there is some argument to proceed with androgen ablation as the sole modality of treatment. The data using this approach are limited, but an understanding of the degree and duration of response is helpful in selecting patients for primary androgen ablation.     

晚期前列腺癌内分泌治疗药物的疗效观察

目的 观察比较晚期前列腺癌内分泌治疗中比卡鲁胺与氟他胺的药物疗效及不良作用情况.方法 回顾分析行内分泌治疗的晚期前列腺癌患者136例,其中黄体生成素释放激素类似物(LHRHa)联用比卡鲁胺间歇性内分泌治疗52例(A组);行LHRHa联用氟他胺间歇性内分泌治疗60例(B组);单纯行睾丸切除24例(C组).分析比较3组患者在临床症状、血清PSA值、疾病进展风险、生存率、药物不良反应等方面的差异.结果 A、B组症状缓解率分别为80.8%(42/52)和81.7%(49/60),高于C组的70.8%(17/24);A、B组PSA平均值分别由治疗前的133.3(17.9～982.8)、142.6(20.2～1001.0)ng/ml下降到15.8(0.02～28.9)、16.1(0.07～53.8)ng/ml,较C组由治疗前的142.3(27.1～988.0)ng/ml下降到27.6(6.0～62.1)ng/ml下降得更多;A、B组生化复发率分别为34.6%(18/52)和36.7%(22/60),低于C组的58.3%(14/24);A、B组平均生化复发时间为22(5～52)和22(6～65)个月,长于C组的11(5～54)个月;A、B组病死率分别为26.9%(14/52)和31.7%(19/60),低于C组的66.7%(16/24).服用比卡鲁胺组持续用药的患者占88.5%(46/52),服用氟他胺组持续用药者占66.7%(40/60).比卡鲁胺组药物不良反应发生率低于氟他胺组.结论 氟他胺和比卡鲁胺均可以有效治疗前列腺癌,降低治疗前列腺癌进展的风险;比卡鲁胺治疗前列腺癌更安全、有效,值得临床推广.     

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.     

Photodynamic therapy in localised prostate cancer

Photodynamic therapy is based on the administration of an energy source in form of light of a specific wavelength, on a previously photosensitized tissue by a chemical compound, in the presence of oxygen, so that the great deal of free radicals and oxygen derivatives generated (hydroxyl compounds) produces necrosis of the treated tissue. Technique improvement during the last years has allowed its recent development as a therapeutic method for localised prostate cancer. At present, several clinical trials are ongoing in patients with organ-confined prostate cancer both as a first line and salvage treatment. There is no risk either of cancer dissemination in surrounding tissues or accumulative pharmaco-toxicity. Therefore, the technique can be repeated as often as needed and can be administered on a previously irradiated tissue. The literature review shows that photodynamic treatment will become a therapeutic option for patients with prostate cancer in the very near future.     

晚期前列腺癌内分泌治疗后血清PSA、f-PSA含量的变化

目的探讨前列腺癌(PCa)患内分泌治疗后前列腺特异抗原(PSA)、游离前列腺特异抗原与总前列腺特异抗原比值(f／tPSA)变化的临床意义。方珐测定PCa患内分泌治疗前及治疗后1、3、6个月血清PSA、游离前列腺特异抗原(f-PSA)变化。砖杲治疗后1个月与治疗前相比血清PSA下降明显，治疗后6个月较治疗后1个月血清PSA下降亦有显意义；治疗后患血清f-PSA水平明显下降。f／tPSA值的变化无显意义。结论血清PSA、f-PSA可作为判断PCa内分泌治疗效果的标准．如血清PSA、f-PSA复又升高提示肿瘤复发。