国人前列腺炎、前列腺增生与前列腺癌的关系

目的:探讨国人前列腺炎、前列腺增生与前列腺癌的关系,为预防决策提供依据.方法:分别以"前列腺炎"、"前列腺增生"、"前列腺癌"等为检索词,收集1979年1月～2007年6月国内公开发表的关于国人前列腺疾患与前列腺癌的研究文献,并用RevMan 4.2软件对这些文献进行Meta分析;根据固定效应模型和随机效应模型计算结果的一致程度进行敏感性分析.结果:纳入本次Meta分析的文献共有4篇,累计病例487例,对照1850例.前列腺炎、前列腺增生与前列腺癌发生的并发相对危险度(OR)值为4.69及95%可信区间(95%CI)为0.60～6.10(P<0.05).结论:前列腺炎,前列腺增生是国人前列腺癌发病的危险因素.     

胰腺癌联合动脉切除术的安全性与疗效Meta分析

目的 系统评价胰腺切除术中采用联合动脉切除对围术期风险及预后的影响。方法 在PubMed、Embase、The Cochrane Library、知网、万方数据库中检索所有比较联合动脉切除的胰腺切除和单纯胰腺切除的回顾性队列研究。按照拟定的纳入标准与排除标准对文献进行筛选；文献质量评价参考纽卡斯尔-渥太华量表标准进行评价；Meta分析运用RevMan 5.2 版软件，采用固定模型分析。结果 共纳入13 篇文献。Meta分析结果显示：与单纯胰腺切除组相比，联合动脉切除组总并发症发生率更高（OR1.66，95%CI 1.25～2.21，P=0.0005），围术期病死率更高（OR 2.91，95%CI 1.43～5.95，P=0.003），术中输血率更高（OR 2.72，95%CI 1.75～4.23，P＜0.00001），切缘阴性率更低（OR 0.45，95%CI 0.31～0.65，P＜0.0001），术后生存率更低（1年：OR 0.57，95%CI 0.39～0.84，P=0.005；3年：OR 0.37，95%CI 0.21～0.65，P=0.0006）。结论 本次Meta分析表明，胰腺癌联合动脉切除术将面临更高的围术期风险和更差的生存率，需谨慎、有针对性地应用该技术。     

放化疗与化疗对局部进展期胰腺癌治疗的Meta分析

目的 :使用Meta分析技术评价放化疗联合治疗与单独化疗对局部进展期胰腺癌(LAPC)的效果。方法:通过数据库检索相关文献到2016年8月,选择治疗组为放化疗联合组,对照组为单独化疗组的LAPC随机对照试验(RCT),由3位评价者分别检索收集资料,按纳入标准筛选文献。应用RevMan5.3.5软件对生存率及并发症发生率进行分析。使用随机效应模型或固定效应模型计算合并的相对危险度(OR)及其95%可信区间(95%CI)。结果:5个研究符合纳入标准,共593例,其中295例为联合放化疗组,298例为单纯化疗组。两组6、12、18、24个月的总生存率相比差异无统计学意义(OR=1.13、1.15、1.13、1.07,95%CI:0.60～2.17、0.53～2.5、0.43～2.95、0.67～1.72)。但放化疗联合组却有较高的3～4级副作用发生率(恶心及呕吐:OR=2.74,95%CI:1.36～5.52;腹泻:OR=4.28,95%CI:1.16～15.71)。结论:在治疗LACP中放化疗联合并不优于单纯化疗,且副作用较多。但由于数据有限,临床应用中应谨慎对待。     

经直肠剪切波弹性成像对前列腺癌诊断价值的Meta分析

目的采用Meta分析评价经直肠剪切波弹性成像在前列腺癌诊断中的应用价值。方法检索2016年12月以前有关经直肠剪切波弹性成像诊断前列腺癌的中、英文文献,按照诊断性试验的纳入标准筛选文献,采用Meta-Disc 1.4及Stata 12.0软件对纳入的文献进行Meta分析。结果共纳入8篇文献,其中经直肠剪切波弹性成像诊断前列腺癌的研究有5篇,汇总分析后,其诊断前列腺癌的合并敏感度(SEN)为0.80[95%CI(0.75,0.84)],合并特异度(SPE)为0.75[95%CI(0.71,0.79)],阳性似然比(PLR)为3.60[95%CI(2.57,5.05)],阴性似然比(NLR)为0.17[95%CI(0.08,0.37)],SROC曲线下面积(AUC)为0.895。经直肠剪切波弹性成像辅助下穿刺诊断前列腺癌的研究亦是5篇,汇总分析后,其合并SEN为0.86[95%CI(0.83,0.88)],SPE为0.84[95%CI(0.82,0.85)],PLR为5.81[95%CI(3.07,10.99)],NLR为0.14[95%CI(0.04,0.49)],SROC曲线下面积(AUC)为0.924。结论经直肠剪切波弹性成像在前列腺癌诊断中有较好临床应用价值,且可作为经直肠超声引导下前列腺穿刺的辅助方法。     

血清前列腺健康指数在前列腺癌诊断中预测活检结果价值的Meta分析

目的:系统评价血清前列腺健康指数(PHI)在前列腺癌(PCa)诊断中预测前列腺穿刺活检的临床价值。方法:检索PubMed(1966~2014年)、中国学术期刊全文数据库(CNKI,1982~2014年),维普期刊资源整合服务平台(1989~2014年)、Cochrane图书馆(1999~2014年)等数据库,检索年限均从建库至2014年2月,收集数据库中血清PHI在PCa诊断中预测活检结果的相关文献;制定相关文献的纳入、排除标准及检索策略,并对纳入文献进行数据提取和质量评价;采用MetaDise 1.4软件进行Meta分析。结果:共检索到相关文献64篇,排除52篇,符合纳入标准的12篇文献进行Meta分析,其中PCa病例组为1 430例,正常或前列腺增生对照组为2 159例。各研究之间存在异质性。按照随机效应模型计算,血清PHI检测在PCa诊断中预测前列腺穿刺活检结果的合并敏感性、特异性、阳性似然比、阴性似然比、诊断比值比、汇总受试者工作特征曲线下面积SROC、Q*指数分别为:55.1%(95%CI:0.525~0.577)、71.5%(95%CI:0.695~0.734)、2.379(95%CI:1.922~2.943)、0.515(95%CI:0.428~0.619)、5.268(95%CI:3.870~7.170)、0.757 8、0.699 9。结论:血清PHI检测在PCa诊断方面能够起到一定的辅助诊断作用,可以成为一种新型的可预测前列腺穿刺活检结果的检测方法。     

多西他赛单药或联合血管内皮生长因子抑制剂治疗去势抵抗性前列腺癌疗效和安全性的Meta分析

目的系统评价多西他赛联合血管内皮生长因子抑制剂治疗去势抵抗性前列腺癌的疗效和安全性。方法计算机检索EMbase、PubMed、Cochran,查找多西他赛单独与联合血管内皮生长因子抑制剂(inhibition of VEGF Agents)比较治疗前列腺癌的随机对照试验(RCT),检索时限均从建库至2014年9月1日。按照纳入/排除标准对纳入研究进行资料提取、方法学质量评价后,采用RevMan 5.2软件进行Meta分析,并采用Jadad评分进行文献质量评估。结果共纳入4个RCT,2 386例患者。Meta分析结果显示,多西他赛联合血管内皮生长因子抑制剂治疗组与多西他赛单药组比较,前列腺特异性抗原(PSA)反应率[RR=0.94,95%CI(0.77,1.15),P=0.56],客观反应率[RR=0.91,95%CI(0.46,1.80),P=0.79],在中位总生存时间方面[HR=0.94,95%CI(0.85,1.04),P=0.23],和无疾病进展时间[HR=1.13,95%CI(0.53,2.38),P=0.76],两组差异无统计学意义;但治疗相关病死率[RR=2.70,95%CI(1.51,4.85),P=0.0009]联合组高于单药组,血栓发生率[RR=0.55,95%CI(0.39,0.78),P=0.0008],联合组低于单药组。结论目前有限证据显示多西他赛联合血管内皮生长因子抑制剂用于治疗去势抵抗性前列腺癌患者方面,并不能提高患者中位总生存和无疾病进展时间,且可能增加治疗相关病死率。上述结论尚需更多高质量大样本RCT加以验证。     

前列腺疾患与前列腺癌关系研究的Meta分析

目的：探讨中国人群前列腺疾患（前列腺炎和前列腺增生）与前列腺癌的关系．为预防决策提供依据。方法：分别以“前列腺炎”、“前列腺增生”和“前列腺癌”等为检索词,收集1979年1月～2005年6月国内公开发表的关于中国人群前列腺疾患与前列腺癌的研究文献,并用RevMan4．2软件对这些文献进行Meta综合定量;根据固定效应模型和随机效应模型计算结果的一致程度及失效安令系数进行敏感性分析。结果：纳入本次Meta分析的文献共有4篇．累计病例487例．对照1850例。前列腺疾患与前列腺癌发生的合并相对危险度（OR）值为4．69及95％可信区间（95％CI）为0．60～6．10,P〈0．05。结论：前列腺炎、前列腺增生是前列腺癌发生的危险因素。     

输精管结扎术与前列腺癌发病风险关系的Meta分析

目的:评价输精管结扎术与前列腺癌发病风险的关系。方法:以"前列腺癌"、"输精管结扎术"及其同义、近义词为关键词,在CBMDisc、CMCC、CMAC、CNKI(1978年至2009年1月6日)和PubMed(1965年至2009年1月6日)等国内外数据库上进行全面检索,按文献纳入及剔除标准筛选出符合要求的文献,提取出相关数据,以RevMan4.2进行一致性检验后采取随机效应模型对纳入研究的文献进行综合定量分析,求出合并OR值及95%CI,并分层分析结扎年限<20年和≥20年与前列腺癌发病风险的OR值及95%CI。结果:共有27篇文献纳入研究,其中队列研究7篇,病例对照研究20篇,共收集研究对象252594例,其中病例20088例,对照232506例。合并OR值(95%CI)为1.10(0.97～1.24),分层分析显示结扎年限<20年和≥20年的合并OR值(95%CI)分别为0.94(0.83～1.06)和1.05(0.90～1.23)。结论:现有研究表明输精管结扎术不会增加前列腺癌的发病风险。     

前列腺癌树突状细胞疫苗的安全性、有效性评价及其临床效果相关因素分析

目的:对文献进行Meta分析,评价树突状细胞疫苗(DC疫苗)治疗前列腺癌的安全性及临床有效性,探讨疫苗临床获益率相关性的因素。方法:根据Cochran协作网制定的策略,使用Medline数据库进行英文检索,根据纳入和排除标准,收集前列腺癌DC疫苗治疗的随机对照试验(RCT),对符合检索条件的文献进行系统评价,文献质量评价和数据提取由2名评价员独立完成,使用RevMan 5.0和SPSS17.0软件进行分析。结果:共有10篇RCT的文献共179例前列腺癌患者临床资料纳入Meta分析,前列腺癌DC疫苗临床获益率(CBR)为54.2%,客观缓解率(完全缓解+部分缓解+混合疗效)为7.7%;仅有轻微不良反应,多为注射部位的局部反应、发热、流感样症状等。分析结果显示:前列腺癌患者给予DC疫苗后出现细胞免疫反应(OR=31.12,95%CI=5.52～175.6,P<0.01)和PSA对数斜率降低(OR=4.38,95%CI=1.17～16.35,P=0.03)与临床获益呈正相关,疫苗剂量(OR=5.98,95%CI=1.45～24.62,P=0.01)对临床获益率有显著影响;患者年龄(P=0.53)与临床获益无相关性。此外,密度富集法获得的DC临床获益率更高;给药途径与临床获益率无相关性。结论:前列腺癌DC疫苗是治疗前列腺癌的有效手段,安全性高,耐受性良好。研究发现前列腺癌DC疫苗介导的细胞免疫反应对临床获益率有显著影响,免疫反应可作为疫苗疗效评价的主要指标。但由于可纳入研究的文献数较少,需要大样本多中心、研究质量高的RCT以明确更好的循证证据。     

PSA及F/T对中国人群前列腺癌早期诊断的系统评价

目的 评价前列腺特异性抗原(prostate-specific antigen,PSA)及游离PSA与总PSA的比值(F/T)在中国人群前列腺癌早期诊断中的价值. 方法 以MEDLINE、中国生物医学文献数据库、中国生物医学期刊文献数据库、中国学术期刊全文数据库与中文科技期刊全文数据库为主进行文献检索,再根据已发表文献中的参考文献追溯进行手工检索.检索期限为1990年1月到2005年6月.按确定的纳入标准筛选文献,对纳入的文献进行质量评价,运用Cochrane协作网诊断与筛查小组推荐的SROC曲线法,对PSA分别以＞4 ng/ml、＞10 ng/ml以及F/T＜0.15作为临界点的敏感度、特异度、准确性、SROC曲线下面积(AUC)等指标行Meta分析. 结果 共检索到69篇中文文献,4篇英文文献.其中10篇文献,共2 256例病例符合纳入标准.PSA分别以＞4 ng/ml、＞10 ng/ml以及F/T＜0.15作为临界点对诊断前列腺癌的敏感度分别为90%、65%和69%;特异度分别为58%、87%和82%;SROC AUC分别为80%、85%和86%. 结论 以PSA F/T＜0.15作为诊断前列腺癌的界值,具有较高的鉴别准确性,尚可应用于中国人群.     

Neoadjuvant hormonal therapy before radical prostatectomy and risk of prostate specific antigen failure

PURPOSE: To date there is little information on the long-term effect of neoadjuvant hormonal therapy on prostate cancer progression. We performed a prospective study to determine whether patients with prostate cancer receiving neoadjuvant hormonal therapy before radical prostatectomy (hormonal therapy group) have a lower risk of prostate specific antigen (PSA) failure than those treated with radical prostatectomy alone (prostatectomy group). We also evaluated whether type of neoadjuvant hormonal therapy and duration were associated with the risk of PSA failure. MATERIALS AND METHODS: We followed 680 men initially treated for prostate cancer with radical prostatectomy between January 1988 and December 1997 at our university hospital. Of the patients 292 received neoadjuvant hormonal therapy. Median followup was 38 months. Cox regression analysis was used to assess the association between neoadjuvant hormonal therapy and PSA failure (greater than 0.3 ng./ml.) controlling for age, clinical stage, grade, initial PSA and adjuvant therapies. RESULTS: Surgical margins were positive less often in the hormonal therapy (25%) than the prostatectomy (47%) group (p = 0.0001). PSA failure was observed in 163 patients and the 5-year failure rate was 33%. No difference in risk of PSA failure was observed overall between the hormonal therapy and prostatectomy groups (hazards ratio 0.94, 95% confidence interval 0.68 to 1.30). Treatments with antiandrogen alone for any duration, and those combining antiandrogen and luteinizing hormone-releasing hormone analogue for 3 months or less were not associated with improved survival. However, patients receiving combined therapy for more than 3 months had a significantly lower risk of PSA failure than those treated with radical prostatectomy alone (hazards ratio 0.52, 95% confidence interval 0.29 to 0.93). CONCLUSIONS: Prolonged neoadjuvant hormonal therapy combining antiandrogen and luteinizing hormone-releasing hormone analogue may improve disease-free survival after radical prostatectomy.     

ROLE OF EARLY ADJUVANT HORMONAL THERAPY AFTER RADICAL PROSTATECTOMY FOR PROSTATE CANCER

PURPOSE: Recent prospective randomized studies have shown that adjuvant hormonal therapy combined with local treatment can significantly improve overall survival in patients with locally advanced disease. This finding challenges the previous belief that adjuvant hormonal therapy may not be beneficial for minimal stages TxN + M0 or less prostate cancer, particularly when combined with local treatment. We reviewed the benefits of adjuvant hormonal therapy in patients at risk for disease progression, especially when administered after radical prostatectomy. MATERIALS AND METHODS: We retrospectively reviewed the current literature and evaluated clinical information on stage pT3b cancer from a large single institution prostate cancer database to determine the current role of adjuvant hormonal therapy after radical prostatectomy for prostate cancer. RESULTS: Retrospective experimental and clinical studies have proved the impact of adjuvant hormonal therapy for decreasing prostate specific antigen (PSA) and clinical disease progression in patients with regionally limited prostatic cancer. This finding applies to stage pT3b as well as to lymph node positive cancer. Our literature review and current data from the Mayo Clinic database show that adjuvant hormonal therapy after prostatectomy has a significant impact on prostate specific antigen (PSA) progression but it also decreases systemic progression and cause specific death in patients with stage pT3b and lymph node positive disease. After adjusting for preoperative PSA, margins, grade, ploidy and patient age the risk ratio for stage pT3b disease in 707 cases was 0.3 (95% confidence interval 0.2 to 0.7). A recent prospective randomized trial showed a significant decrease in cancer death in N+ cases when adjuvant hormonal therapy was administered after radical prostatectomy, supporting previous Mayo Clinic data on N+ disease that favors combination therapy. In the PSA era, that is 1987 and after, our database data on stage pTxN+ cancer indicates that radical prostatectomy and hormonal therapy for single node positive disease resulted in 94% 10-year cause specific survival, which was not significantly different from the rate in patients with N0 disease after adjusting for local stage, Gleason grade, margins, ploidy, PSA and adjuvant hormonal therapy. CONCLUSIONS: Our literature review, including prospective randomized studies, and more recent results in the PSA era from our database indicate that early adjuvant hormonal therapy has a significant impact on time to progression and cause specific survival in patients with seminal vesicle invasion and limited lymph node disease who undergo radical prostatectomy, although in a retrospective nonrandomized study. Future prospective studies with longer followup are needed to evaluate the potential benefit of adjuvant treatment in regard to survival for stages pT2 and pT3a disease with unfavorable pathological variables.     

Radical prostatectomy for pathological Gleason 8 or greater prostate cancer: influence of concomitant pathological variables.

PURPOSE: We evaluated the long-term outcome of radical prostatectomy for pathological Gleason score 8 or greater prostate cancer and characterized the prognostic significance of other pathological variables. MATERIALS AND METHODS: A total of 6,419 patients underwent radical prostatectomy between 1987 and 1996. There were 407 patients classified as having pathological Gleason 8 or greater, including 8 in 48%, 9 in 49% and 10 in 3%. Adjuvant treatment was used in 45% of patients and adjuvant hormonal therapy was administered to 155 (38%). Progression-free, including local or systemic, and/or prostate specific antigen (PSA) 0.4 ng./ml. or greater, and cancer specific survival were determined by the Kaplan-Meier method. The effect of pathological grade and stage, preoperative PSA, DNA ploidy, margin status, tumor dimension, seminal vesicle invasion, and adjuvant treatment was assessed with the univariate and multivariate analyses. RESULTS: Pathological stage distribution was pT2 in 26% of patients, pT3 48% and pTxN+ 27%. Overall and progression-free survival at 10 years was 67% and 36%, respectively, compared to cancer specific survival 85%. Adjuvant treatment, pathological stage, preoperative PSA and pathological grade were significant (less than 0.05) univariate predictors of progression-free survival. Pathological stage, margin status and ploidy were univariately associated with cancer specific survival. Progression-free survival at 10 years of those patients who did and did not receive adjuvant treatment was 52% and 23%, respectively. In the multivariate analysis pathological grade (p=0.02), preoperative PSA (p <0.0001), adjuvant therapy (p <0.0001) and pathological stage (p=0.036) were significant independent predictors of progression-free survival. CONCLUSIONS: High grade prostate cancer can be controlled with radical prostatectomy in some patients with disease confined pathologically, and 10-year cause specific survival is 96%. Predictors of outcome in patients with Gleason 8 disease or greater are similar to established predictors derived by using all grades. Although adjuvant hormonal therapy appears to improve disease progression rates after radical prostatectomy on the basis of this nonrandomized study, it may not affect prostate cancer death rates within 10 years in patients with high grade cancer.     

Localized prostate cancer. Local treatment and what place for lymphadenectomy

The pretreatment PSA level, the Gleason score, the presence of lymph-node metastases, the status of surgical positive margins are poor pathological risk factors for patients who have a pathologic stage T3 prostate cancer. The increase in PSA level during the year prior to diagnostic is associated with the risk of death due to prostate cancer following radical prostatectomy or external beam radiation therapy. The assessment of Locoregional extension is indicated for such patients. The extended pelvic lymphadenectomy remains the most accurate procedure for a correct staging of the detection of nodal involvement in these patients with high-risk localized prostate cancer. For such patients with a high-risk of progression and, whose the life expectancy is greater than 10 years, treatment must be a combined modality therapy since radical prostatectomy alone correlates with a poor clinical outcome. Adjuvant hormonal therapy following local curative treatment by prostatectomy (or radiotherapy) needs to be often considered. Collegial decision-making is by far the most appropriate setting for the discussion among medical specialists of these complex clinical cases for patients often having associated medical conditions and whose adjuvant treatment will have a significant impact of their future quality of life.     

经尿道前列腺切除术与前列腺癌根治术后生化复发的相关性

探讨经尿道前列腺切除术（TURP）与前列腺癌根治术（RP）治疗前列腺癌(PCa)患者术后生化复发（BCR）的相关性。方法 选取2013年1月至2017年12月就诊于本院的480例接受RP治疗的PCa患者。患者定期随访并完善前列腺特异性抗原（PSA）检测,术后连续2次检测PSA≥0.2 ng/mL定义为BCR,采用多因素Cox风险比例回归模型等方法探索TURP对RP术后BCR发生风险的影响。结果 480例RP患者中有400例患者未行过TURP治疗,80例患者既往行TURP治疗。行TURP治疗过的患者BCR发生时间显著缩短,与未行过TURP治疗的患者比较,差异有统计学意义（P=0.016）。有TURP手术史（HR=2.31,95%CI:1.33～4.04,P=0.003）、PSA升高（HR=1.01,95%CI:1.00～1.02,P=0.007）、T3b分期（HR=2.83,95%CI:1.16～6.87,P=0.022）、Gleason评分为7～9分（7分：HR=2.28,95%CI:1.09～4.75,P=0.028;8分：HR=2.90,95%CI: 1.24～6.80,P=0.014;9分：HR=5.55,95%CI:2.32～13.29,P<0.001）是BCR发生的独立危险因素。结论 在PCa患者中,TURP手术史、PSA升高、T3b分期及Gleason评分7～9分的患者在RP术后发生BCR的风险较高。     

GnRH analogs and prostate cancer treatment

Prostate cancer is currently the main indication of LH-RH analogs. This class, which in recent years has replaced diethylstilbestrol and surgical castration, now plays a major role at all stages of the disease. Numerous studies with contradictory results have compared total hormonal blockage, an alog combined with an anti-androgen, with analog alone in locally advanced prostate cancer. A recent metaanalysis showed a slight though globally non-significant advantage in favour of total blockage, but with a significant advantage in the case of a nonsteroidal anti-androgen. In stage T3 cancers, adjuvant hormone therapy over three years in combination with radiotherapy versus external radiotherapy alone was more effective in terms of local or metastatic progression and survival. Institution during radiotherapy and a prolonged duration of treatment gives a greater benefit though this was only significant for the subgroup of patients with a Gleason score > or = 8. For localized stages but at high risk (PSA > 15 ng / ml and\or Gleason score > 7), adjuvant hormone therapy after prostatectomy improved recurrence-free survival in comparison with prostatectomy followed-up by simple monitoring. On the other hand, the administration of analogs two or three months before radical prostatectomy did not seem to provide any additional benefit. Medical castration prolonged by LH-RH analogs engenders multiple side effects which become all the more worrying as patient survival is prolonged by this hormone therapy. In phase I-II studies, intermittent treatment is equivalent to continuous treatment for "hormone sensitive" patients (PSA nadir at six months < 0.5 ng). Phase III studies are in progress to confirm this equivalence. This intermittent hormone therapy may be a useful solution for elderly patients (> 78 years old) with a biologically highly active cancer and remains to be evaluated in relatively young subjects after radical prostatectomy or radiotherapy. Combination of analogs with chemotherapy has been used very recently for patients who have reached hormonal escape and may be a useful immediate option for patients with cancers with a high risk of progression.     

Treatment results of radical prostatectomy in clinical stage B and C prostate cancer: comparison of the neoadjuvant therapy group versus the surgery group; retrospective analysis of 80 cases

Between 1994 and 2001, 80 patients underwent radical prostatectomy without adjuvant therapy for clinical stage B and C prostate cancer. The patients were not treated with adjuvant therapy before biochemical prostate specific antigen (PSA) failure. Of all 80 patients, 35 patients (43.8%) received neoadjuvant hormonal therapy prior to radical prostatectomy (the neoadjuvant therapy group), 45 patients (56.2%) underwent prostatectomy alone (the surgery alone group). Retrospective analysis to evaluate the effects of neoadjuvant therapy was performed from clinicopathological findings and the biochemical PSA failure-free rate. Of all patients, 58 (72.5%) were in clinical stage B and 22 (27.5%) were in clinical stage C. Of 58 patients in clinical stage B, 19 (32.8%) underwent prostatectomy combined with neoadjuvant therapy. Of the 22 patients in clinical stage C, 17 (77.3%) underwent prostatectomy combined with neoadjuvant therapy. Pathologically, 37 (46.3%) were in stage B, 38 (47.5%) in stage C and 2 (2.5%) in stage D1. Three patients in the neoadjuvant therapy group had no malignant findings in specimens of prostatectomy. In comparison with the clinical stage, pathologically 8 (22.9%) showed overstaging, 4 (5.0%) understaging and 23 (28.8%) accurate staging in the neoadjuvant therapy group, respectively, 0 (0.0%), 20 (44.4%), and 25 (55.6%) in the surgery alone group. In clinical stage B and C, there was no significant difference in the biochemical PSA failure-free rate between the neoadjuvant therapy group and the surgery alone group. On the other hand, in pathological stages B, the 5-year PSA failure-free rate was 63.2% in the neoadjuvant therapy group, but 100% in the surgery alone group. Although neoadjuvant therapy may have some effect on downstaging, our retrospective analysis suggests that it has no significant effect on PSA failure-free rate.     

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.     

Predictive factors of radiation therapy for patients with prostate specific antigen recurrence after radical prostatectomy

OBJECTIVE: To assess the efficacy of salvage/adjuvant radiation therapy (RT) for patients with prostate-specific antigen (PSA) recurrence after radical prostatectomy (RP). PATIENTS AND METHODS: Between 1997 and 2001, 52 patients were treated in our institution with RT for PSA recurrence after RP. The mean (range) delay between RP and RT was 30.5 (0.16-105.6) months. Eighteen patients received no hormonal therapy before RT. The failure of RT was defined as three consecutive increases in PSA levels with intervals of > or = 6 weeks. RESULTS: Within a mean (range) follow-up of 27.7 (6-69) months, 18 patients presented with biochemical progression. The 3-year biochemical progression-free survival was 51%. Using univariate analysis, an age < 65 years (P = 0.0262), a Gleason score on the RP specimen of > or = 8 (P = 0.0024), stage pT3 (P = 0.02), a detectable nadir PSA after RT (P < 0.001) and the absence of hormonal therapy (P = 0.0359) were associated with a lower biochemical progression-free survival. However, only the Gleason score (P = 0.0395) and nadir serum PSA after RT (P = 0.028) remained independent predictive factors on multivariate analysis. CONCLUSION: Half of the present patients treated with RT for an isolated high serum PSA level after RP were free of biochemical relapse at 3 years of follow-up. RT may be proposed to selected patients with mild morbidity. However, definitive evidence of the beneficial effect of adjuvant RT for patients with PSA recurrence after RP awaits the conclusion of randomized clinical trials.     

PSA relapse prostate cancer: the importance of tailored therapy

Prostate specific antigen (PSA) is an invaluable tumor marker in the detection of early prostate cancer as well as a predictor of recurrence after treatment of localized disease. Current practice entails the use of factors such as pretherapy grade, stage and PSA, PSA doubling time, nature of previous therapy and patient age and functional status for a treatment recommendation. For a PSA relapse post radical prostatectomy, radiation therapy to the prostatic fossa is a primary therapeutic consideration. With careful patient selection, about 30 to 40% of patients are rendered disease free using this approach. For patients with radiation therapy as the primary treatment for their prostate cancer, salvage prostatectomy can be considered, but is rarely feasible. Systemic therapy with hormones is standard if patients are not candidates for the above mentioned salvage local therapies or if they relapse after exhaustive local therapies. Unfortunately androgen suppressive therapy is unlikely to induce cure, or prolonged remissions in PSA relapse prostate cancer. The strategy of addition of chemotherapy or biologic therapy to androgen suppressive therapy is under active investigation. The goal of this therapy is to make an impact on the time to progression to metastatic prostate cancer and correspondingly decrease prostate cancer related mortality. Preliminary results of studies incorporating early chemotherapy in combination with androgen suppressive therapy are encouraging, with improvement in time to progression and overall survival. The evaluation of biologic agents and agents with better toxicity profiles is ongoing. This is very important to make therapy widely applicable and to enable prolonged administration especially in a disease such as prostate cancer with a relatively long natural history. Strategies of adjuvant and neoadjuvant therapy in locally advanced prostate cancer are exploring the possibility of reducing the chance of PSA relapse by treating micrometastatic disease. This review discusses the current practices in risk stratification and management of PSA relapse prostate cancer. It also highlights the major clinical trials and areas of active investigation in this field.