前列腺癌的声像特征及血清PSA与Gleason评分、临床分期的相关性研究

目的探讨前列腺癌（PCa）患者的声像图、血清PSA与PCa Gleason评分、临床分期的相关性。方法回顾性分析经直肠超声引导下穿刺活检确诊的220例PCa患者的临床资料和声像图表现。采用Spearman等级相关分析和秩和检验,分析血清PSA水平与Gleason评分、临床分期的关系。结果超声显示有异常回声结节178例,其中145例为低回声结节,42例在声像图上未发现异常。PCa患者Gleason评分越高,临床分期越晚,PSA值越高。血清PSA水平分别与Gleason评分（r=0．275,P〈0．01）、临床分期（r=0．314,P〈0．01）呈正相关;Gleason评分与临床分期亦呈正相关（r=0．325,P〈0．01）。结论前列腺内部低回声结节是PCa主要超声表现,血清PSA与Gleason评分和PCa临床分期有关,该指标可作为判断PCa预后的指标。     

以骨痛症状为首发表现的前列腺癌临床分析：附51例报道

目的 回顾性分析以骨痛为首发症状的前列腺癌患者的临床特点.方法 收集2003～2010年我院51例以骨痛为首发症状的前列腺癌患者,均经前列腺穿刺或骨转移瘤病理证实.骨转移通过静脉注射555 ～ 925 MBq 99mTc-MDP后通过SPECT/CT采集分析证实,部分经骨肿瘤切除或骨穿刺病理证实.所有患者均接受最大限度雄激素阻断的内分泌治疗.统计其骨转移的部位分布以及前列腺特异抗原（PSA）、碱性磷酸酶（ALP）和Gleason评分对骨转移的预测,分析内分泌治疗对骨痛缓解的有效性和生存分析.结果 患者年龄55 ～ 85岁,平均（72.5±8.5）岁.初诊时骨转移的发生率为92.2％ （47/51）.骨盆转移占21.5％,腰椎转移占29.0％,胸椎转移占15.0％,颈椎转移占3.7％.其中PSA ≥20 ng/ml者44例（86.2％）,其骨转移率达100％;DRE检查阳性者39例（76.5％）;Gleason≥8分者20例（39.2％）;cTNM分期≥T3期者39例（76.5％）.经治疗后80％的患者骨痛症状缓解.1年、3年、5年生存率分别为88.7％、67.8％、54.1％.结论中老年男性以骨痛为首发症状的要考虑发生前列腺癌的可能,若患者PSA≥20 ng/ml,DRE触及结节,Gleason≥8分,cTNM分期≥I3期,发生骨转移的机会大.转移以骨盆、腰椎转移率最高.内分泌治疗可有效缓解骨痛和转移进展.PSA与骨转移有关.     

减瘤性前列腺癌根治术联合内分泌治疗在寡转移前列腺癌患者中的疗效及预后观察

目的 探讨减瘤性前列腺癌根治术（cytoreductive radical prostatectomy,CRP）联合内分泌治疗（androgen deprivation therapy,ADT）在寡转移前列腺癌中的手术效果及预后。方法 纳入2015年6月至2021年3月收治的寡转移前列腺癌患者67例，32例行CRP联合ADT治疗（CRP组），35例行单纯ADT治疗（ADT组）。记录CRP组围手术期数据、两组进展至CRPC时间及肿瘤特异性生存期（cancer specific survival,CSS），运用Kaplan-Meier法比较。结果 两组（PSA）水平，Gleason评分，临床T、N分期差异无统计学意义。CRP组Clavien-DindoⅠ级并发症2例，Ⅱ级并发症9例，并发症发生率为34.38%。CRP组20例进展至CRPC，中位进展时间为26个月，ADT组21例进展至CRPC，中位进展时间为19个月。两组激素依赖性生存期差异有统计学意义（P <0.001）。Cox多因素回归分析显示CRP是延长寡转移前列腺癌进展至CRPC的独立保护因素（HR=0.276,95%CI:0...     

以骨痛为首发症状的前列腺癌生存预后分析

目的回顾性分析以骨痛为首发症状骨转移性前列腺癌患者的临床特点,统计分析年龄、穿刺前前列腺特异抗原（PSA）、Gleason评分、有无转移及骨转移数目、临床分期、碱性磷酸酶等对患者整体生存预后的影响。方法收集2003至2010年51例以骨痛为首发症状的骨转移性前列腺癌患者,均经前列腺穿刺或骨转移瘤病理证实。骨转移通过静脉注射555-925MBq 99mTc—MDP后通过SPECT／CT采集分析证实,部分行骨转移肿瘤切除或骨穿刺病理证实。所有患者均接受最大限度的雄激素阻断的内分泌治疗（手术去势或药物去势联合抗雄激素（氟他胺50mg／d,比卡鲁胺50mg／d）。结果以骨痛为首发症状的前列腺癌发生骨转移率较高,为92．2％（47／51）,骨盆、腰椎转移率较高,分别为21．5％、29．0％。中位随访时间为32．1个月,至随访结束有20例患者死亡,中位整体生存期为24．4个月。患者年龄（≥71岁vs．〈71岁）与生存预后存在相关性（23．1个月VS．29．1个月,P=0．0169）：穿刺前PSA值（≤100ng／ml vs．〉100ng／m1）与生存预后无相关性（36．7个月坩．19．4个月,P=0．1797）;Gleason评分（2～6,7,8～10）与整体生存预后有明显的相关性（62．4个月vs．35．1个月w．12．5个月,P=0．0173）,骨转移数目（〈6个vs．≥6个）与患者整体生存时间具有相关性（36．1个月vs．4．4个月,P=0．0144）;仅有骨转移及骨转移伴有精囊侵犯、肺、淋巴等转移与患者整体生存有相关性（25．7个月1;S．4．4个月,P=0．0304）;临床分期（≤T2w．≥T3）与患者生存预后具有相关性（62．4个月vs．23．1个月,P=0．0257）;碱性磷酸酶（正常坩．升高）与整体生存期明显相关（37．0个月VS．19．0个月,P=0．0151）。一线治疗生化复发的时间为（17．6±8.3）个月,一线治疗失败后予更换成比卡鲁胺治疗后治疗有效率为54．5％（24／44）。结论对于以骨痛为首发症状的骨转移性前列腺癌患者,年龄、骨转移的数目、脏器、淋巴转移、临床分期、碱性磷酸酶、Gleason评分能预测患者的整体的生存预后（P〈0．05）。MAB是较为有效的治疗方式,一线治疗生化复发后二线内分泌治疗部分患者仍可获益。     

经直肠超声造影联合MRI评估前列腺癌骨转移的应用价值

目的 探讨经直肠超声造影联合MRI评估前列腺癌骨转移的应用价值。方法 选取我院经超声引导下前列腺穿刺活检证实的95例前列腺癌患者,均行经直肠超声、超声造影、MRI及骨扫描检查,根据骨扫描结果分为骨转移组38例和非骨转移组57例,比较两组临床资料、经直肠超声造影参数、表观弥散系数（ADC）的差异。采用多因素Logistic回归分析前列腺癌骨转移的影响因素;绘制受试者工作特征（ROC）曲线分析经直肠超声造影联合MRI评估前列腺癌骨转移的价值。结果 两组年龄、体质量指数、前列腺体积及上升时间、达峰时间、平均渡越时间、上升支斜率比较差异均无统计学意义;骨转移组Gleason评分、前列腺特异性抗原（PSA）水平、血清碱性磷酸酶（ALP）水平、峰值强度（PI）、曲线下面积（AUC）均高于非骨转移组,强度降半时间（IHT）及ADC均低于非骨转移组,差异均有统计学意义（均P<0.05）。多因素Logistic回归分析显示,Gleason评分、PSA水平、ALP水平、PI、AUC均为前列腺癌骨转移的独立危险因素（OR=1.549、1.224、1.102、1.189、1.006,均P<0.05...     

PSAD用于前列腺癌危险因素分析的价值

[目的]探讨血清前列腺特异性抗原密度（PSAD）与前列腺癌危险因素之间的相关性,评估其用于分析前列腺癌危险因素的价值.[方法]检测70例前列腺癌患者血清前列腺特异性抗原（PSA）水平,利用经直肠B超测定患者的前列腺体积,根据PSA与前列腺体积的比值计算出PSAD,依据PSAD值将其分为：0.01～0.15,0.16～0.20,0.21～0.5 和大于0.51 ng/（mL·cm3）四组.根据Gleason评分和临床分期将以上70例患者分为低、中、高危三组,分别分析PSAD与Gleason评分、临床分期之间的相关性.[结果]PSAD与Gleason评分、临床分期呈显著正相关,随着PSAD的升高,前列腺癌的危险度也相应升高（P〈0.05）;同时,PSAD值升高,其骨显像阳性率也相应升高.[结论]PSAD可作为临床参考指标用于前列腺癌危险因素的分析,用于判断前列腺癌预后     

重视激素难治性前列腺癌的化学治疗

前列腺癌是老年男性中较为常见的疾病,主要治疗方法是内分泌治疗,经治疗后大部患者可获得病情好转,然而,在经过中位时间为18～24个月的缓解期后,原来对内分泌治疗敏感的前列腺癌,常常转为激素难治性前列腺癌（hormonal refractory prostate cancer,HRPC）。HRPC的定义必须同时满足以下条件：①血浆睾酮达到去势水平（通常定义去势水平为〈50ng／ml）;②连续3次间隔2周测得的血清PSA递次上升;③停用抗雄药物至少4周（康士得需停药至少6周）;④在应用二线内分泌治疗的情况下,PSA仍持续上升;或出现骨或软组织病灶继续进展。过去,由于晚期前列腺癌对化疗不敏感,且缺乏确切的疗效评价指标以及受化疗本身的毒副作用等因素的限制,HRPC的化疗一直不为人们所重视。近5年来,由于对前列腺癌的发病机制以及化疗药物的作用机理有了进一步的认识,化疗再次成为HRPC的研究热点,并已成为目前治疗HRPC的主要方法。本文将就这方面的进展作一介绍。     

2型糖尿病患者微量白蛋白尿进展为严重肾病的危险因素分析

目的：探讨2型糖尿病患者微量白蛋白尿进展为严重肾病的危险因素。方法：随机选取2型糖尿病患者114例,按尿白蛋白／肌酐（UA1b／Cr）分为4组,健康对照组77例,采用免疫比浊法测定尿白蛋白／肌酐,采用高分辨率彩色多普勒超声仪测量颈动脉内膜-中层厚度（IMT）,用简化MDRD方程计算肾小球滤过率（GFR）,并对各组数据进行统计分析。结果：Logistic回归分析显示：矫正年龄、病程因素后,在微量白蛋白尿期,糖化血红蛋白（HBA1C）、收缩压（SBP）为UA1b／Cr的独立危险因素,Exp（B）分别为1．028（95YooCI1．009—1．047P：0．004）、1．314（95％CI 1．102—1．567P=0．002）;在临床蛋白尿期,SBP、餐后2h血糖（PPG）、胆固醇（TC）、GFR、IMT为UA1b／Cr的独立危险因素,Exp（B）分别为：1．057（95％CI 1．017—1．099P：0．005）、1．228（95％CI 1．027—1．469,P=0．024）、2．666（95％CI 1．296—5．485,P=0．008）、0．95（95％CI 0．932—0．978,P=0．00）、22．703（95％CI2．199—234．35,P：0．009）。结论：IMT是促进2型糖尿病肾病进展的极强的危险因素,IMT的增厚是微量蛋白尿向临床蛋白尿转化的关键因素。     

影响进展期胃癌根治术后早期复发的相关因素分析

【目的】分析影响进展期胃癌根治术后早期复发的相关因素,为临床干预工作提供依据。【方法】选取2008年3月至2011年4月本院收治的195例进展期胃癌患者作为研究对象,所有患者均接受胃癌根治术治疗,根据患者术后1年内复发与否将上述患者分为早期复发组（n=103）与对照组（n=92）。先后采用χ2检验、非条件Logistic回归分析确定影响进展期胃癌根治术后早期复发的独立相关因素。【结果】①单因素分析发现,两组患者的肿瘤直径、Borrmann分型、Lauren分型、T分期、N分期、TNM分期、新辅助化疗、术后化疗等指标相比差异有统计学意义（P〈0．05）,两组患者的性别、年龄、体质指数、肿瘤位置、分化程度、手术方式、腹腔镜手术等指标相比差异无统计学意义（P〉0．05）。②非条件Logistic回归发现,N分期、TNM分期是影响进展期胃癌根治术后早期复发的独立危险因素,而新辅助化疗是独立保护因素。【结论】进展期胃癌的N分期、TNM分期是其术后早期复发的独立危险因素,采取而新辅助化疗可降低进展期胃癌根治术后早期复发率。     

前列腺癌组织肝激酶B1，Rab鸟嘌呤核苷酸交换因子-5mRNA表达水平与临床病理特征和预后的相关性研究

目的　研究前列腺癌患者癌组织中肝激酶B1（liver kinase B1,LKB1）及Rab鸟嘌呤核苷酸交换因子-5 (Rab guanine nucleotide exchage factor-5,Rab EX-5) mRNA表达及临床意义。方法　应用实时荧光定量PCR（qRT-PCR）检测92例前列腺癌组织和80例良性前列腺增生组织中LKB1及RabEX-5 mRNA的表达,比较LKB1,RabEX-5 mRNA表达组间差异及与临床病理特征的关系。Pearson线性相关分析LKB1与RabEX-5 mRNA表达的相关性。Kaplan-Meier生存分析LKB1,RabEX-5 mRNA表达与前列腺癌患者生存预后的关系。多因素COX回归分析影响前列腺癌患者生存预后的危险因素。结果　与前列腺增生组织相比,前列腺癌组织中RabEX-5 mRNA表达明显升高（1.311±0.374 vs 0.457±0.083）,差异有统计学意义（t=20.758,P=0.000）,而LKB1 mRNA表达显著降低（0.373±0.052 vs 1.234±0.268）,差异有统计学意义（t=30.181,P=0.000）。LKB1,RabEX-5 mRNA表达与Gleason评分、骨转移、TNM分期有关（t=2.419~9.965,均P<0.05）,与年龄、前列腺特异抗原（PSA）水平无关（t=0.379~1.453,均P>0.05）。前列腺癌组织中LKB1与RabEX-5 mRNA的表达呈显著负相关（r=-0.402,P=0.000）。低LKB1表达组3年总体生存率低于高LKB1表达组（χ2=55.605,P=0.000）,高RabEX-5表达组3年总体生存率低于低RabEX-5表达组（χ2=29.435,P=0.000）。多因素COX回归分析结果表明,Gleason评分≥7分（OR=2.671,P=0.018）、骨转移（OR=1.528,P=0.031）、TNM分期为Ⅲ期（OR=1.634,P=0.037）,LKB1 mRNA低表达（OR=1.764,P=0.008）及RabEX-5 mRNA高表达（OR=2.587,P=0.000）是影响前列腺癌患者生存预后的危险因素（P<0.05）。结论　前列腺癌组织中RabEX-5 mRNA表达升高,而LKB1 mRNA表达降低,二者共同参与前列腺癌的发生发展,有望成为评估前列腺癌患者预后的组织肿瘤标志物。     

癌组织lncRNA H19和血清前列腺特异抗原水平与前列腺癌病理特征及预后的相关性

目的分析癌组织长链非编码RNA(lncRNA)H19和血清前列腺特异抗原(PSA)水平与前列腺癌(PCa)病理特征及预后的相关性。方法选取89例PCa患者作为病例组,选取同期100例良性前列腺增生患者作为对照组,对两组患者术中切除前列腺组织lncRNA H19相对表达量和血清PSA水平进行检测。结果病例组患者病灶组织中lncRNA H19相对表达量和血清PSA水平均高于对照组。高lncRNA H19表达组患者的总生存期(OS)和无进展生存期(PFS)均低于低lncRNA H19表达组(P<0.05)。Cox风险回归模型分析结果显示,前列腺患者术后OS与病灶组织lncRNA H19相对表达量、临床分期、淋巴结转移情况、Gleason评分、分化程度具有相关性;术后PFS与病灶组织lncRNA H19相对表达量、淋巴结转移情况、Gleason评分具有相关性(P<0.05)。结论PCa癌组织中存在lncRNA H19相对表达量上调,其表达水平与肿瘤的病理特征和患者的预后具有相关性,可作为预测患者预后的辅助指标和潜在治疗靶点,患者术前血清PSA水平虽与病理特征具有相关性,但与患者的预后缺乏相关性。     

Stratification of patient risk based on prostate-specific antigen doubling time after radical retropubic prostatectomy

OBJECTIVE: To assess the risk of local recurrence, systemic progression, and death from cancer among patients who experience biochemical relapse after radical retropubic prostatectomy and to stratify those patients by prostate-specific antigen (PSA) doubling time (DT). PATIENTS AND METHODS: We identified patients who experienced biochemical recurrence (defined as a PSA level < or =0.4 ng/mL) after radical prostatectomy from January 1, 1990, to December 31, 1999, for prostate adenocarcinoma. The PSA-DT was calculated by log linear regression using all PSA values within 2 years of biochemical recurrence. Local recurrence- and systemic progression- free survival and cancer-specific survival were estimated using the Kaplan-Meier method and analyzed by the log-rank test and Cox models. RESULTS: Biochemical recurrence was noted in 1521 (27%) of 5533 men during the follow-up period. Of the 1064 patients with a calculable PSA-DT, 322 (30%) had a PSA-DT of less than 1 year, 357 (34%) had a PSA-DT of 1 to 9.9 years, and 385 (36%) had a PSA-DT of 10 years or more. Patients with a PSA-DT of 10 years or more were less likely to have a higher preoperative PSA level, Gleason score, advanced pathologic stage, and seminal vesicle invasion. Patients with a PSA-DT of 10 years or more were at low risk of local recurrence (hazard ratio [HR], 0.09; 95% confidence interval [CI], 0.06-0.14; compared with patients with a PSA-DT of <1 year), systemic progression (HR, 0.05; 95% CI, 0.02-0.13), or death from cancer (HR, 0.15; 95% CI, 0.05-0.43). CONCLUSIONS: Prostate-specific antigen DT is an independent predictor of clinical disease recurrence and mortality after surgical biochemical failure. Risk stratification into high-, intermediate-, and low-risk categories based on the PSA-DT provides helpful clinical information and assists in the development of salvage therapy trials.     

PSA doubling time as a predictor of clinical progression after biochemical failure following radical prostatectomy for prostate cancer

OBJECTIVES: To characterize the clinical progression of disease in men who have undergone prostatectomy for clinically localized prostate cancer and have postoperative biochemical failure (elevated prostate-specific antigen [PSA] level) and to identify predictors of clinical disease progression, including the possible effect of PSA doubling time (PSADT). PATIENTS AND METHODS: Between 1987 and 1993, 2809 patients underwent radical retropubic prostatectomy for clinically localized (< or =T2) disease. In our database, all patients with postoperative biochemical failure (PSA level > or =0.4 ng/mL) were identified. The PSADT was estimated using log linear regression on all PSA values (excluding those values determined after administration of hormonal therapy) within 15 months after biochemical failure. All patients had regular PSA measurements from the time of surgery through the follow-up period. Systemic progression (SP) was defined as evidence of metastatic disease on a bone scan. Local recurrence (LR) was defined on the basis of digital rectal examination, transrectal ultrasonography, and biopsy. The SP-free survival and LR/SP-free survival (survival free of both LR and SP) after biochemical failure was estimated with use of the Kaplan-Meier method. Patients with prostate cancer treatment after biochemical failure had their follow-up censored from this study at the time of treatment. RESULTS: Postoperative biochemical failure occurred in 879 men (31%). The mean follow-up from time of biochemical failure was 4.7 years (range, 0.5-11 years). The mean time to biochemical failure was 2.9 years (median, 2.4 years). The overall mean SP-free survival from time of biochemical failure was 94% and 91% at 5 and 10 years, respectively. The mean LR/SP-free survival was 64% and 53% at 5 and 10 years, respectively. By using univariate analysis on the 587 patients with PSADT data, significant risk factors for SP were PSADT (P<.001) and pathologic Gleason score (P=.005); for LR/SP, significant risk factors included PSADT (P<.001) and pathologic Gleason score (P<.001). In multivariate Cox models analysis, only PSADT remained a significant risk factor for both SP and LR/SP (P<.001). Mean 5-year SP-free survival was 99%, 95%, 93%, and 64% for patients with PSADT of 10 years or longer, 1.0 to 9.9 years, 0.5 to 0.9 year, and less than 0.5 year, respectively; the respective mean LR/SP-free survivals were 87%, 62%, 46%, and 38%. The percentage of patients with PSADT of less than 0.5 year was considerably higher if the type of first clinical event was SP (48%) compared with LR (18%) (P<.001). CONCLUSIONS: For patients who have undergone radical prostatectomy, a rising PSA level suggests evidence of residual or recurrent prostate cancer. Many men remain free of clinical disease for an extended time after biochemical failure following radical prostatectomy for clinically localized prostate cancer. The PSADT appears to be an important predictor of SP and also of any clinical progression (local or systemic). These data may be useful when counseling men regarding the timing of adjuvant therapies.     

基于PI-RADS V2.1评分构建诺莫图预测PSA“灰区”前列腺癌的价值研究

目的探讨基于前列腺影像报告和数据系统版本2.1(PI-RADS V2.1)评分联合前列腺特异性抗原(PSA)及其他临床变量构建诺莫图对PSA"灰区"前列腺癌的预测价值。方法回顾性分析陕西省人民医院2016年10月~2021年10月204例行多参数MRI检查并有病理学结果的患者资料。单因素和多因素Logistic回归分析患者的年龄、体质指数(BMI)、总PSA(tPSA)、游离PSA(fPSA)、游离/总PSA(f/tPSA)、PSA密度(PSAD)、前列腺体积、直肠指诊(DRE)、PI-RADS V2.1评分与前列腺癌的相关性。确定预测PSA"灰区"前列腺癌的独立危险因素,使用R软件构建诺莫图预测模型。并通过绘制ROC曲线比较诺莫图模型与其他独立预测因素的诊断效能。结果PSAD、体积、PI-RADS V2.1评分、年龄和tPSA是预测"灰区"前列腺癌的独立危险因素。基于上述5个临床指标构建的诺莫图模型AUC值最高,为0.896。其他临床独立指标中,PI-RADS V2.1评分AUC值最高(0.854),年龄、体积、PSAD、tPSA的AUC值分别为0.625、0.706、0.739、0.615。结论基于PI-RADS V2.1联合临床指标建立的个体化诺莫图预测模型,可用于预测血清PSA处于"灰区"的前列腺癌,有助于减少不必要的穿刺。     

前列腺癌近距离治疗疗效

  目的  探讨前列腺癌患者近距离治疗疗效及并发症。  方法  前列腺癌患者27例, 年龄63~81岁, 平均75岁。临床分期:T1cN0M016例, T2aN0M011例; Gleason评分:5分14例, 6分13例; 血清前列腺特异性抗原(prostate specific antigen, PSA)2.8~14.6 μg/L, 平均8.5 μg/L。采用¹²⁵I粒子近距离治疗, 治疗剂量D90为140~155 Gy, 观察治疗疗效及并发症。27例患者治疗前后均未使用内分泌治疗。  结果  27例患者随访12~74个月, 平均44个月。近距离治疗后27例前列腺癌患者最低血清PSA中位数为0.18 μg/L, 2例患者最低血清PSA在1.0 μg/L以上; 治疗后1年患者血清PSA中位数为0.71 μg/L, 平均为0.92 μg/L, 17例患者血清PSA在1.0 μg/L以下; 2例患者分别于治疗后30及48个月出现生化复发, 复发率7%(2/27)。治疗后2例患者出现急性尿潴留, 予保留导尿1周后好转; 24例治疗后出现不同程度的尿路刺激症, 均在治疗后6~12个月内好转; 无1例出现前列腺直肠瘘。治疗前17例有勃起功能; 治疗后10例仍保留不同程度的勃起功能, 7例出现勃起功能障碍(占41%)。  结论  前列腺癌近距离治疗对于中低危前列腺癌疗效肯定, 并发症少, 多数患者可以保留性功能。     

Chemotherapy for prostate cancer

The clinical significance of chemotherapy for patients with hormone refractory prostate cancer(HRPC) is still controversial. Some randomized-controlled trials represented that mitoxantrone combined with prednisone (or hydrocortisone) provided palliative benefit to patients with HRPC. These treatments are well tolerated by elderly patients. On the other hand, the high PSA response rates have been observed in trials with both estramustine and taxane, however, higher toxicity was also recognized. The most relevant endpoint is not only palliative efficacy but also survival in these trials. Recently, the improvement of survival with docetaxel-based chemotherapy was reported. Further studies with chemotherapeutic agents will be needed to provide patients of HRPC good quality of life and longer survival.     

Evidence-based medical perspectives: the evolving role of PSA for early detection, monitoring of treatment response, and as a surrogate end point of efficacy for interventions in men with different clinical risk states for the prevention and progression of prostate cancer

Following FDA approval and introduction into the clinic in the mid-1980s, PSA testing has become arguably the most versatile serum tumor marker in urologic oncology with clinical use for early detection (screening) of prostate cancer (PC), risk stratification for clinical staging, prognosis, intermediate biomarker for monitoring tumor recurrence, and more recently as an intermediate biomarker for assessing therapeutic response to antiandrogens, radiation therapy, and chemotherapy. PSA now routinely guides health care providers for the clinical management of PC over a wide range of clinical risk states for men at risk of PC, after local definitive therapy and after systemic therapy to prevent progression to metastatic bone disease, and to palliate men with hormone refractory prostate cancer (HRPC). To further assess the evidence that supports these clinical applications, this commentary reviews and critically evaluates the emerging body of new data focusing on several recently published seminal articles by D'Amico et al and Thompson et al, the new National Comprehensive Cancer Network 2004 recommendations for starting PSA testing at the age of 40 years old, the latest results from 2 phase 3 randomized, controlled trials of taxane-based regimens showing improved survival for men with HRPC, and the recent US FDA Public Workshop on Clinical Trial Endpoints in Prostate Cancer that helped to distill and synthesize the current state of the art and the progress toward validation of PSA metrics (eg, PSA velocity) as a surrogate end point (SE) for treatment efficacy with taxane-based regimens. Furthermore, several randomized, controlled chemoprevention trials in progress evaluating agents such as selenium and vitamin E in high-risk cohorts are well poised to confirm the validity of PSA as an SE for clinical efficacy for the prevention and progression of PC. Although there continues to be a need to validate better biomarkers before diagnosis of PC (more sensitive and specific) and after diagnosis to discern between indolent and aggressive forms of PC, it is very likely that some metric of PSA as a biomarker alone or as part of a panel of other serum proteomic markers or tissue-derived multiplex gene expression arrays will be around for years to come as a useful tool for risk stratification, early detection, prognosis, prediction, and as an SE of efficacy for prevention and treatment of PC.     

Fluorescence in situ hybridization aneuploidy as a predictor of clinical disease recurrence and prostate-specific antigen level 3 years after radical prostatectomy

OBJECTIVE: To determine if fluorescence in situ hybridization (FISH) analysis of fresh-tissue biopsy specimens obtained at the time of radical prostatectomy is able to predict prospectively clinical disease progression or prostate-specific antigen (PSA) level in patients 3 to 4 years after surgery. MATERIALS AND METHODS: FISH analysis was performed on fresh-tissue touch preparations obtained from 90 randomly selected radical prostatectomy specimens. Cut surface touch preparations from 40 specimens resected in 1992 were analyzed with DNA probes for chromosomes 4, 6-12, 17, 18, X, and Y. Needle-biopsy specimens were obtained from 50 tumors resected in 1993, and touch preparations from these specimens were studied with DNA probes for chromosomes 7, 8, 11, and 12. Serum PSA levels and clinicopathologic data were recorded, and each patient was followed up from the time of surgery to determine cancer progression. RESULTS: Of 90 patients undergoing radical prostatectomy in 1992 and 1993, 89 returned for follow-up. Three patients received preoperative hormonal therapy, and in 2 patients, antiandrogen therapy was continued postoperatively. Fifteen patients underwent intraoperative orchiectomy immediately after radical prostatectomy, while 9 patients had postoperative adjuvant hormonal therapy. Six patients underwent postoperative radiation therapy. Fourteen patients (15.7%) demonstrated systemic, local, or PSA progression. Only 2 (4.7%) of 43 patients with FISH diploid tumors demonstrated cancer progression. Conversely, 10 (30.3%) of 33 FISH aneuploid and 12 (26.1%) of 46 FISH nondiploid tumors demonstrated cancer progression (P=.004 and P=.006, respectively). Unlike FISH, flow cytometric aneuploidy was not associated with early cancer progression. Elevated preoperative PSA concentration, increased preoperative and postoperative Gleason score, and increased preoperative and postoperative T or N stage were not statistically significantly associated with cancer progression. While chromosome 7 and 8 aneusomies were not statistically associated with cancer progression, 2 of 5 (P=.04) chromosome 12 aneusomic tumors demonstrated cancer progression. CONCLUSION: Early (within 4 years) local, systemic, or PSA progression occurred more frequently (P<.05) in radical prostatectomy patients with FISH aneuploid, nondiploid, and chromosome 12 aneusomic tumors. Flow cytometric ploidy status, preoperative serum PSA concentration, and clinical or pathologic grade or stage, including seminal vesicle involvement, margin status, and capsular perforation status, were not associated with early prostate cancer progression in this group of 89 patients. FISH analysis appears to be a useful preoperative tool for predicting aggressive vs indolent prostate cancer.     

Delay in the progression of low-risk prostate cancer: rationale and design of the Reduction by Dutasteride of Clinical Progression Events in Expectant Management (REDEEM) trial

PURPOSE: Men with prostate cancer may live as long as men their age without prostate cancer. Those with low-risk disease may benefit from expectant management, which actively monitors disease progression. Dutasteride, a dual 5alpha-reductase inhibitor (5ARI), may delay prostate cancer progression or extend the time to initiation of more aggressive therapy. MATERIALS AND METHODS: The Reduction by Dutasteride of Clinical Progression Events in Expectant Management (REDEEM) trial will evaluate whether dutasteride decreases time to prostate cancer progression. Three hundred candidates for expectant management with biopsy-proven, low-risk, localized prostate cancer will receive dutasteride 0.5 mg/day or placebo for 3 years. Eligible men are between 50 and 80 years of age, have clinical stage T1c-T2a prostate cancer, a Gleason score of less than or equal to 6, and serum prostate-specific antigen (PSA) less than or equal to 10 ng/mL. Entry biopsy of at least 10 cores had to be performed within 6 months of screening and will be repeated at 1.5 and 3 years. Men will complete questionnaires to measure symptoms, quality of life (QOL), and anxiety. Because PSA is an important monitoring tool in expectant management that may impact patients' comfort levels, actual PSA values will be provided to physicians and subjects. Time-to-disease progression (primary therapy for prostate cancer or pathologic progression), positive cores, change in Gleason score, and QOL assessments will be compared between groups. RESULTS: The trial completed recruitment of 302 subjects in March 2007. The study will be completed in 2010. CONCLUSIONS: The REDEEM study will evaluate the potential for dutasteride to delay disease progression in men with low-risk, localized prostate cancer. This study will better define which patients with prostate cancer can be managed with less invasive and potentially less debilitating therapy.