应用前列腺特异抗原筛查诊断前列腺癌的临床意义

目的 探讨应用前列腺特异抗原(PSA)筛查诊断前列腺癌的临床意义.方法 对年龄≥50岁的8562例男性体检者进行PSA筛查,对血清PSA≥4.0 ng/ml者建议进行经直肠前列腺系统活检,活检病理确诊为前列腺癌的患者人选筛查组,记录其临床病理特点,并与同时期临床诊治的82例前列腺癌患者(临床组)进行比较.结果 在8562例进行血清PSA筛查的男性中,有719例血清PSA水平≥4.0 ng/ml,其中295例接受经直肠前列腺系统活检,共检出前列腺癌58例,活检率和活检阳性率分别为41.0%和19.7%.虽然两组患者的年龄分布差异无统计学意义(P=0.176),但筛查组中有41.4%(24/58)的患者年龄＞75岁,明显高于临床组(25.6%,P=0.0491).筛查组中血清PSA水平≥20.0 ng/ml的患者所占的比例为44.8%,明显低于临床组(75.6%,P＜0.0001).筛查组中活检Gleason评分＜7分的患者所占的比例为60.3%,明显高于临床组(34.1%,P=0.0020).筛查组中临床分期为T1和T2期(局限期)患者所占的比例为87.9%,明显高于临床组(26.8%,P＜0.0001).筛查组中接受根治性前列腺切除术的患者所占的比例为50.0%,明显高于临床组(18.3%,P＜0.0001).在年龄≤75岁的患者中,筛查组患者诊断时的血清PSA水平、活检Gleason评分和临床分期均显著低于临床组(均P＜0.05);在年龄＞75岁的患者中,筛查组患者的临床分期也明显低于临床组(P=0.0002),但两组诊断时血清PSA水平和活检Gleason评分的差异并无统计学意义(均P＞0.05).结论 应用血清PSA在我国50岁以上男性中进行前列腺筛查是有效的.筛查出的前列腺癌患者在血清PSA水平、活检Gleason评分、临床分期以及根治性切除的机会等方面均较临床组有明显优势.     

前列腺特异抗原正常进展型前列腺癌的临床特点分析

 目的　探讨正常水平血清前列腺特异抗原（PSA）进展型前列腺癌的临床特点。方法　回顾性分析12例血清PSA值为0～4 ng／ml并确诊为前列腺癌患者的临床资料。患者年龄60～77岁,平均67.5岁。B型超声检查发现阳性5例,后经前列腺穿刺活组织检查确诊;5例经尿道前列腺电切术,术后病理确诊;2例骨扫描异常,后经前列腺穿刺活检确诊。结果　T1期6例,T2a期3例,T3期1例,M1b 期2例;Gleason评分：2～4分2例,5～7分3例,8～10分7例。随访11例,术后3、6、9个月内分别死亡7、10、11例。结论　血清PSA水平为0～4 ng／ml进展型前列腺癌症状相对较轻,多数肿瘤细胞分化低,病情进展快,转移早,预后差。     

TRIM29联合PSA在前列腺癌诊断中的应用

目的:探讨TRIM29在前列腺癌的表达情况,并讨论其异常表达与前列腺癌Gleason评分、骨转移等临床病理特征间的关系以及TRIM29联合前列腺癌特异性抗原(prostate specific antigen,PSA)检测在前列腺癌诊断中的应用前景。方法:56例经病理确诊的前列腺癌患者为实验组,25例良性前列腺增生(benign prostatic hyperplasia,BPH)患者为对照组。应用免疫组化和Western blot法检测TRIM29蛋白表达水平,检测患者外周血PSA水平。二元回归法分析PSA、TRIM29相关诊断性能。结果:正常前列腺基底细胞均可见TRIM29表达,而前列腺癌组织则呈低表达,Western blot结果提示前列腺组织中TRIM29表达水平明显低于正常前列腺组织(P<0.01),在前列腺伴发骨转移患者中TRIM29表达水平低于不伴骨转移患者(P=0.038),TRIM29表达水平与前列腺患者Gleason评分密切相关,TRIM29表达与PSA无相关性,其诊断效价略优于PSA(P=0.041)。结论:TRIM29低表达与前列腺癌发生关系密切,可作为前列腺诊断的潜在靶点,辅助PSA达到早期诊断前列腺的目的。     

联合间歇性内分泌与125I放射性粒子植入术治疗局部晚期前列腺癌(附20例报告)

目的:探讨联合125I放射性粒子植入术和间歇性内分泌治疗局部进展期前列腺癌的临床价值.方法:前列腺癌患者20例,年龄52～80岁,中位年龄74岁,PSA:6.83～643.8ng/mL,Gleason Score:7～9分,临床分期T3NOM0.连续硬膜外麻醉,截石位,直肠超声从前列腺基底到尖部进行扫描,图像传送至计算机计划系统进行三维重建和术中计划,根据计划行直肠超声引导下经会阴125I放射性粒子植入术,术后结合雄激素全阻断疗法.当PSA达到0ng/mL,并稳定2个月后停止内分泌治疗,当PSA连续3次上升,则重新开始内分泌治疗.结果:所有患者手术均顺利,术中使用穿刺针26～36根,植入粒子57～99粒,平均73粒.术后随访8～51个月,平均22月.1例术后16个月发生骨转移,1例术后22个月死亡.术后3～5个月所有患者的PSA都降到正常范围,其中3例PSA未达到0ng/mL,未停药.4例术后5～26个月,出现PSA反弹,再次用药3～5个月PSA值达到0ng/mL:目前12例未出现PSA反弹,第一周期脱离治疗时间2～44个月,平均16.9个月.近期出现的并发症有轻至中度尿路刺激症30%(6/20),急性尿潴留5%(1/20),直肠刺激症和血便25%(5/20),多数患者症状随访1年后缓解.目前18例患者的PSA值在0～1.2ng/mL之间,其中17患者PSA≤0.17ng/mL.结论:对于局部晚期前列腺癌,125I放射粒子植入术结合间歇性内分泌是一种安全有效的治疗方法.     

tPSA<4ng/ml前列腺癌的临床特点分析(附35例报告)

目的探讨总PSA(tPSA)<4 ng/m l的前列腺癌(PC a)患者的临床特点。方法回顾性分析35例tPSA<4 ng/m l并经病理确诊为前列腺腺癌患者的临床特征及病理特点。结果35例PC a患者年龄均>60岁,因排尿困难就医,2例伴肉眼血尿者并发膀胱肿瘤。直肠指诊(DRE)触及前列腺结节者仅1例(2.9%),前列腺质地硬者仅10例(28.6%)。B超示35例患者前列腺包膜均完整,其中16例(45.7%)前列腺回声不均匀,平均体积为34.3 m l,<40 m l者比例达82.9%(29/35)。患者临床病理分期均在T2b以下,其中T1期31例(88.6%),T2期4例(11.4%)。G leason评分2~5分30例(85.7%),6分2例(5.7%),7~8分3例(8.6%)。结论前列腺癌有可能发生于tPSA<4 ng/m l的老龄人群中,此类患者的前列腺体积一般较小,临床病理分期相对较低,分化程度相对较好。     

根治性前列腺切除术后病理大切片与常规切片的对比分析

背景与目的：在根治性前列腺切除术(radical prostatectomy,RP)组织标本中,应用病理大切片技术可以全面观察组织,其在病理诊断、形态学研究方面拥有独特的优势。但是由于制作技术、设备限制、工作量较大等原因,目前在临床上尚未常规开展。本研究通过比较RP后行常规切片及病理大切片患者的临床及病理变量,评价RP后病理大切片技术在前列腺癌诊断中的意义。方法：选择2012年12月-2014年2月在复旦大学附属肿瘤医院行RP后做病理大切片的229例前列腺癌患者作为研究组,同时选取2010年1月-2012年6月行RP后做常规病理切片的393例前列腺癌患者作为对照组,对比分析包括两组患者年龄,术前PSA值,术前是否接受新辅助内分泌治疗,前列腺癌确诊方式,确诊时Gleason评分、临床分期,RP后Gleason评分、病理分期、手术切缘、前列腺包膜外侵犯、精囊侵犯、术后盆腔淋巴结转移等变量。结果：两组患者术前临床及病理变量：RP后病理Gleason评分、病理分期、前列腺包膜外侵犯情况、术后盆腔淋巴结转移差异均无统计学意义(P>0.05),但是研究组患者手术切缘及精囊侵犯的阳性率明显高于对照组,差异有统计学意义(26.2% vs 17.6%,P=0.010;23.1% vs 17.0%,P=0.025)。结论：应用病理大切片技术可明显提高前列腺标本切缘阳性及精囊侵犯的阳性检出率,因此病理大切片技术值得在前列腺癌病理诊断中推广。     

误诊为膀胱癌的前列腺癌12例临床分析

目的:提高对前列腺癌基底部肿瘤的正确认识,规范前列腺癌的诊断,避免前列腺基底部肿瘤误诊为膀胱肿瘤。方法:收集并回顾性分析2003年4 月～2010年4 月本院收治的12例入院前误诊为膀胱癌的前列腺癌患者的临床资料。结果:本组患者平均年龄70.5 ± 7.8 岁,PSA 平均为43.62ng/mL。12例均行直肠指诊（DRE ）发现前列腺质硬8 例,质韧4 例,Ⅱ° 肿大者7 例,Ⅲ°肿大5 例,可及结节5 例。9 例行MRI 检查其中8 例考虑为前列腺癌累及膀胱,1 例考虑为前列腺癌。12例行前列腺穿刺活检（6 针法）结果均为前列腺腺癌,Gleason评分:7～8 分。临床分期T4N1M1b 7 例,T4N0M0 5 例。结论:多方位、多角度的影像学检查,重点观察前列腺结构是否紊乱,对称性是否消失,包膜是否完整,膀胱壁连续性是否存在,并联合PSA 、DRE 等检查,必要时行前列腺穿刺活检,有助于前列腺基底部肿瘤的正确诊断,对前列腺癌与膀胱癌鉴别诊断有重要价值。      

PSA、FPSA检测和骨显像对前列腺癌骨转移的诊断价值

目的:探讨联合应用前列腺特异性抗原(PSA)、游离PSA(FPSA)检测和全身骨显像诊断前列腺癌骨转移的意义.方法:回顾性分析70例经临床确诊的前列腺癌患者,全部行血清PSA、FPSA测定,并作全身骨显像.结果:PSA<4ng/ml在14例病人中,发生骨转移者7例,诊断阳性率为50%;PSA 4ng/ml～20ng/ml共7例,发生骨转移者6例,诊断阳性率为87%;PSA＞20ng/ml组49例,发生骨转移45例,阳性率为92%.结论:PSA、FPSA检测结合全身骨显像,可尽早、全面地发现前列腺癌患者全身骨转移.     

海南地区Gleason评分≥7分的前列腺癌患者血清PSA和睾酮水平与预后相关性探讨

目的:分析海南地区Gleason评分≥7分的前列腺癌（prostatic cancer,PCa）患者血清前列腺特异性抗原(prostate specific antigen,PSA)和总睾酮（total testosterone,TT）水平与5年总生存率的相关性。方法:回顾性分析2009年01月至2019年12月我院收治的前列腺癌患者106例作为PCa组,选取同期良性前列腺增生症（benign prostatic hyperplasia,BPH）患者120例作为BPH组,比较两组患者临床资料、血清PSA、TT水平;再根据PCa组患者5年生存情况分为生存组（n=81）和死亡组（n=25）,比较两组患者临床资料、Gleason评分、血清PSA、TT水平;采用多因素COX回归分析影响前列腺癌患者预后的独立危险因素;绘制受试者工作特征曲线（receiver operating characteristic curve,ROC）,分析血清PSA、TT水平早期评估前列腺癌患者预后的预测价值;采用Spearman相关性模型分析血清PSA、TT水平与病理Gleason评分的相关性。结果:PCa组患者年龄、前列腺体积、血清PSA水平高于BPH组,血清TT水平低于BPH组,差异具有统计学意义（P＜0.05）;生存组患者Gleason评分、血清PSA水平、骨转移发生率、TNM分期低于死亡组,血清TT水平高于死亡组,差异具有统计学意义（P＜0.05）;Spearman相关性分析显示,血清PSA水平与病理Gleason评分呈正相关（r=0.634,P＜0.05）,血清TT水平与病理Gleason评分呈负相关（r=-0.755,P＜0.05）;多因素COX回归分析显示,高PSA水平（HR=1.352）、高Gleason评分（HR=4.576）、高TNM分期(HR=2.937)和骨转移（HR=1.258）是前列腺癌患者预后的独立危险因素（P＜0.05）,高TT水平（HR=0.063）是前列腺癌患者预后的保护因素（P＜0.05）;ROC曲线显示,血清PSA、TT水平及两者联合早期预测前列腺癌患者预后的曲线下面积（area under curve,AUC）为0.811、0.887和0.934,敏感度为88.00%、96.00%和92.00%,特异度为68.73%、72.84%和82.72%,截点值分别为21.51 ng/mL和3.74 ng/mL。结论:前列腺癌患者血清PSA、TT水平可作为早期评估患者预后的重要指标,其与病理Gleason评分存在高度相关性。     

术前低PSA的Gleason 8~10分前列腺癌患者临床特点

背景与目的:前列腺癌的发病率逐渐上升,其中有些患者在诊断为高级别前列腺癌甚至转移性前列腺癌时,其前列腺特异性抗原(prostate-specific antigen,PSA)数值却处于很低的水平。探讨术前低血清PSA的Gleason 8~10分前列腺癌患者临床特点。方法:收集2013年1月-2018年1月江苏省苏北人民医院收治的72例接受前列腺癌根治术的高Gleason评分前列腺癌患者的临床资料。根据术前血清PSA水平分为4组:A组<4.0 ng/mL(9例)、B组4.0~10.0 ng/mL(12例)、C组10.0~20.0 ng/mL(15例)和D组>20.0 ng/mL(36例)。4组平均年龄分别为(68.8±8.6)、(68.9±6.0)、(71.6±6.0)和(68.4±6.4)岁。平均随访时间分别为(21.6±12.1)、(18.8±7.2)、(25.0±13.4)和(24.8±12.5)个月。切缘阳性例数分别为3例(33.3%)、5例(41.7%)、5例(33.0%)和15例(41.7%)。精囊侵犯例数分别为6例(66.7%)、2例(16.7%)、2例(13.3%)和14例(38.9%)。淋巴结转移例数分别为2例(22.2%)、3例(25.0%)、4例(26.7%)和13例(36.1%)。预后评价指标为无生化复发天数(biochemical progression-free day,bPFD)与前列腺癌特异性死亡(prostate cancer-specific death,PCSD)。4组平均PFD分别为(90.00±38.40)、(306.17±79.00)、(223.14±63.30)和(145.03±62.50)d。PCSD例数分别为4例(44.4%)、0例(0.0%)、1例(6.7%)和5例(13.9%)。组间年龄、随访时间、PFD使用单因素方差分析,进一步两两比较采用最小显著差别(least significant difference,LSD)法;组间临床病理学特征采用χ2检验、Fisher精确检验;PCSD使用Kaplan-Meier生存分析,生存曲线间比较使用log-rank检验。结果:A组与其余3组相比,年龄、随访时间、切缘阳性、淋巴结转移的差异均无统计学意义(P>0.05)。A组与B、C两组相比,精囊侵犯、PFD的差异均有统计学意义(P<0.05)。但A组与D组相比,精囊侵犯、PFD的差异无统计学意义(P>0.05)。生存分析显示,A组相较于B组在随访时间内生存状况更差,但差异无统计学意义(P=0.092),A组与C、D两组的生存差异有统计学意义(P<0.05)。结论:具有术前低血清PSA水平的高Gleason评分前列腺癌患者相较于PSA更高水平的患者预后更差,易出现精囊侵犯、术后生化复发快且PCSD例数多。     

Prostate-specific antigen velocity and the detection of gleason score 7 to 10 prostate cancer

BACKGROUND: An increasing prostate-specific antigen (PSA) velocity is associated with a shorter survival after local therapy for prostate cancer. In this study, the authors evaluated whether PSA velocity was associated with prostate cancer detection and grade at diagnosis after adjusting for established predictors. METHODS: Between January 1989 and December 2003, 914 men who had PSA levels >/=4 ng/mL were identified by using the Center for Prostate Disease Research (CPDR) multicenter national database, including 541 men who were diagnosed with prostate cancer. Multivariable logistic regression analyses were performed that included continuous variables (PSA velocity and level, number of prior negative biopsies, and age) along with categorical variables (ethnicity and family history) were used to identify the factors associated with prostate cancer detection and grade. RESULTS: An increasing PSA velocity was associated with Gleason scores from 7 to 10 versus Gleason scores form 2 to 6 or no cancer (adjusted odds ratio [OR], 1.04 ng/mL per year; 95% confidence interval [95% CI], 1.003-1.085 ng/mL per year; P = .035). This finding was not evident in patients who had prostate cancers with Gleason scores between 2 and 6 or for any prostate cancer. PSA level was associated with the detection of any prostate cancer (OR, 1.06 ng/mL; 95% CI, 1.03-1.10 ng/mL; P = .004) and Gleason score 4 ng/mL. These findings, in conjunction with life expectancy, may be used when deciding which men should not be recommended for prostate biopsy despite a PSA level >4 ng/mL.     

Bone scanning--who needs it among patients with newly diagnosed prostate cancer?

BACKGROUND: We evaluated the relationship between serum PSA and clinical variables to eliminate bone scanning in patients with prostate cancer having a low probability of bone metastasis. METHODS: The study included 366 patients with newly diagnosed prostate cancer between 1999 and 2005. Bone metastasis was studied for its correlation with various clinical and pathological variables in these patients. RESULTS: Bone metastasis was found in 28 (7.7%) of 366 patients. Fourteen patients had skeletal symptoms related to bone metastasis. The risk for bone metastases increased considerably with increases of PSA level, clinical T stage and Gleason score. The metastasis was not found in 161 patients with serum PSA concentration of 10 ng/ml or lower. In 95 patients with the concentration between 10 and 20 ng/ml only two had the metastasis. These two patients had T2 disease and Gleason scores of 7 or greater. In 204 patients with clinical stage T1 disease, one (0.5%) had the metastasis. In 117 patients with Gleason scores of 6 or less, the metastasis was found in two (1.7%). CONCLUSIONS: For patients with serum PSA levels of 10 ng/ml or lower, bone scanning may be eliminated because of the negligible risk of bone metastases. In addition, scanning may not be necessary for those with PSA levels between 10 and 20 ng/ml, when they have T1 disease and Gleason scores of 6 or lower.     

以尿潴留为首发表现的前列腺癌临床分析（附43例）

目的:回顾分析以尿潴留为首发表现的前列腺癌患者的临床特点。方法:收集我院2001年7月至2014年7月以尿潴留为首发症状的前列腺癌患者43例,均经前列腺穿刺活检确诊。3例患者接受腹腔镜下腹膜外前列腺癌根治术,其余40例患者均接受经尿道前列腺电切术（transurethral resection of prostate,TURP）联合内分泌治疗［（最大限度雄激素阻断（maximal androgen blockade,MAB）］。统计其年龄分布、前列腺特异性抗原（prostate specific antigen,PSA）、直肠指检(digital rectal examination,DRE)阳性率、经直肠前列腺穿刺阳性针数、Gleason评分、骨转移、肿瘤分期、治疗后排尿恢复情况、IPSS评分及1年、3年、5年生存率。结果:43例患者的年龄中位数为69岁;直肠指检阳性率达81.4%（35/43）;PSA＞20 ng/ml者占62.8%（27/43）;经直肠前列腺穿刺（12+X针穿刺法）超过7针以上阳性的占76.7%（33/43）;Gleason评分≥7分占95.3%（41/43）;骨转移患者占76.7%（33/43）;临床分期T3b-T4期占88.4%（38/43）;治疗后6个月全部患者恢复了自主排尿,1年生存率为97.7%,3年生存率为79.1%,5年生存率为55.8%。结论:老年男性发生尿潴留应当考虑有前列腺癌的可能性,该类前列腺癌患者病程往往多为晚期且为高危患者,肿瘤压迫侵犯尿道及膀胱颈是排尿困难的主要原因,经尿道前列腺电切术联合内分泌治疗,可有效解除下尿路梗阻,控制肿瘤进展,提高患者生活质量。     

Prostate-specific antigen velocity and prostate cancer gleason grade and stage

BACKGROUND: Increased preoperative prostate-specific antigen (PSA) velocity (PSAV) has been associated with increased prostate cancer mortality and higher Gleason scores. The authors evaluated the relation between PSAV, biopsy Gleason score, and pathologic stage in men who were enrolled in a prostate cancer screening trial. METHODS: Data were analyzed from 1441 men who were enrolled in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial who received > or =2 PSA screens and were diagnosed with prostate cancer within 1 year of the last screen. PSAV was estimated by using all screening PSA values within 6 years prediagnosis. RESULTS: Both PSA and PSAV were related to biopsy Gleason score. The multivariable odds ratios (OR), controlling for PSA and demographics, for having a Gleason score of 7 to 10 were 1.3 (95% confidence interval [95% CI], 0.9-1.9), 2.2 (95% CI, 1.5-3.3), and 2.3 (95% CI, 1.4-3.9) for men with PSAV values from 0.5 to 1 ng/mL per year, from 1 to 2 ng/mL per year, and >2 ng/mL per year, respectively, compared with men who had PSAV values <0.5 ng/mL per year. The median PSAV was 0.60 ng/mL per year for men with Gleason scores from 2 to 6 versus 0.84 ng/mL per year for men with Gleason scores from 7 to 10 (P < .0001). Among 658 men who underwent prostatectomy, both PSA and PSAV were associated with advanced pathologic stage in univariate analyses; however, when the analysis controlled for clinical stage and biopsy Gleason score, the associations of PSA and PSAV were no longer statistically significant. CONCLUSIONS: PSAV and PSA levels were associated independently with biopsy Gleason score. Among men who underwent prostatectomy, PSAV and PSA were not predictive of advanced pathologic stage when the analysis was controlled for biopsy Gleason score and clinical stage. It cannot be determined yet whether PSAV is predictive of long-term prostate cancer outcome in this cohort.     

Australian prostate‐specific antigen outcome and toxicity following radiation therapy for localized prostate cancer

The objective of the present study was to examine prostate‐specific antigen relapse free survival (PSA‐RFS) and morbidity following ‘conventional’ radical radiation therapy for prostate cancer in two Australian regional treatment services. Four hundred and eighty men with clinically localized prostate cancer were treated between 1993 and 1997 at Liverpool and Westmead Hospitals using a standardized 4‐field, CT‐planned radiotherapy technique. Principal endpoints were PSA‐RFS (American Society for Therapeutic Radiology and Oncology guidelines definition) and late rectal and urinary morbidity (Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer criteria). The median follow up of patients from the end of RT was 55 months. Prospectively, they were divided into three prognostic categories: (i) high risk T3 or 4 and/or PSA > 20 ng/mL and/or Gleason score 8?10 (40% of cohort); (ii) intermediate risk T1 or 2 and PSA 10?20 ng/mL and/or Gleason score 7 (33% of cohort); and (iii) low risk T1 or 2 and PSA < 10 ng/mL and Gleason score < 6 (27% of cohort). The 5‐year actuarial PSA‐RFS was 53% for the whole patient group. The 4‐year rates were 32, 56 and 75% for high, intermediate and low risk groups, respectively. On multivariate analysis, T‐stage, Gleason score, pre‐RT‐PSA were strong independent predictors of PSA‐defined outcome. Late (grade 2) rectal and urinary morbidity occurred at some point in time in the post‐RT period in 8.0 and 5.8% of patients, respectively. These results confirm that low Gleason score, low T stage, presenting PSA < 10 ng/mL and nadir < 1 ng/mL remain the strongest predictors of a good outcome. Long‐term toxicity was very acceptable. However, further improvement in outcome is desirable, and with the adoption of new technology allowing escalation of radiotherapy doses such an expectation might be achieved.     

Phase II trial of neoadjuvant docetaxel and gefitinib followed by radical prostatectomy in patients with high‐risk,locally advanced prostate cancer

BACKGROUND:

Prostate cancer trials investigating neoadjuvant hormonal therapy, followed by surgery, have demonstrated that elimination of all tumor cells from the primary site is rare. The authors report a phase 2 trial assessing the efficacy and toxicity of docetaxel and gefitinib in patients with high‐risk localized prostate cancer as neoadjuvant therapy before radical prostatectomy (RP).

METHODS:

Thirty‐one patients with high‐risk prostate cancer were treated with docetaxel and gefitinib for 2 months before RP. All patients met the criteria of clinical stage T2b‐3 or serum prostate‐specific antigen (PSA) level >20 ng/mL, or Gleason score of 8 to 10. The primary endpoint was pathologic complete response. Secondary objectives included clinical response. When available, endorectal coil magnetic resonance imaging (eMRI) was performed as part of clinical response evaluation. Immunohistochemical staining of epidermal growth factor receptor and HER‐2/neu was performed on prechemotherapy and postchemotherapy prostate tissue.

RESULTS:

The median age of the patients was 60 years, the median pretreatment PSA level was 7.43 ng/mL, and the median Gleason score was 8. Clinical staging prior to treatment consisted of: T1 in 4 patients, T2 in 17 patients, and T3 in 10 patients. One patient with enlarged pelvic adenopathy and T4 disease did not undergo RP. Thirty patients received all scheduled therapies including RP. Grade 3 toxicities included asymptomatic liver function test elevation in 4 (13%) patients, diarrhea in 1 (3%) patient, and fatigue in 1 (3%) patient. One patient experienced grade 4 toxicity with elevated alanine aminotransferase. RP specimen pathology demonstrated residual carcinoma in all cases. Twenty‐nine (94%) patients achieved a clinical partial response, including 35% of patients who demonstrated radiographic improvement on eMRI.

CONCLUSIONS:

No pathologic complete response was noted in 31 patients treated with docetaxel and gefitinib. This combination was well tolerated, and did not result in increased surgical morbidity. Cancer 2009. © 2009 American Cancer Society.     

PSA nadir predicts biochemical and distant failures after external beam radiotherapy for prostate cancer: a multi-institutional analysis

PURPOSE: To determine the significance of prostate-specific antigen (PSA) nadir (nPSA) and the time to nPSA (T(nPSA)) in predicting biochemical or clinical disease-free survival (PSA-DFS) and distant metastasis-free survival (DMFS) in patients treated with definitive external beam radiotherapy (RT) for clinical Stage T1b-T2 prostate cancer. METHODS AND MATERIALS: Nine participating institutions submitted data on 4839 patients treated between 1986 and 1995 for Stage T1b-T2cN0-NxM0 prostate cancer. All patients were treated definitively with RT alone to doses > or =60 Gy, without neoadjuvant or planned adjuvant androgen suppression. A total of 4833 patients with a median follow-up of 6.3 years met the criteria for analysis. Two endpoints were considered: (1) PSA-DFS, defined as freedom from PSA failure (American Society for Therapeutic Radiology and Oncology definition), initiation of androgen suppression after completion of RT, or documented local or distant failure; and (2) DMFS, defined as freedom from clinically apparent distant failure. In patients with failure, nPSA was defined as the lowest PSA measurement before any failure. In patients without failure, nPSA was the lowest PSA measurement during the entire follow-up period. T(nPSA) was calculated from the completion of RT to the nPSA date. Results: A greater nPSA level and shorter T(nPSA) were associated with decreased PSA-DFS and DMFS in all patients and in all risk categories (low [Stage T1b, T1c, or T2a, Gleason score < or =6, and PSA level < or =10 ng/mL], intermediate [Stage T1b, T1c, or T2a, Gleason score < or =6, and PSA level >10 but < or =20 ng/mL, or Stage T2b or T2c, Gleason score < or =6, and PSA level < or =20 ng/mL, or Gleason score 7 and PSA level < or =20 ng/mL], and high [Gleason score 8-10 or PSA level >20 ng/mL]), regardless of RT dose. The 8-year PSA-DFS and DMFS rate for patients with nPSA <0.5 ng/mL was 75% and 97%; nPSA > or =0.5 but <1.0 ng/mL, 52% and 96%; nPSA > or =1.0 but <2.0 ng/mL, 40% and 91%; and nPSA > or =2.0 ng/mL, 17% and 73%, respectively. The 8-year PSA-DFS and DMFS rate for patients with T(nPSA) <6 months was 27% and 66%; T(nPSA) > or =6 but <12 months, 31% and 85%; T(nPSA) > or =12 but <24 months, 42% and 94%; and T(nPSA) > or =24 months, 75% and 99%, respectively. A shorter T(nPSA) was associated with decreased PSA-DFS and DMFS, regardless of the nPSA. Both nPSA and T(nPSA) were significant predictors of PSA-DFS and DMFS in multivariate models incorporating clinical stage, Gleason score, initial PSA level, and RT dose. The significance of nPSA and T(nPSA) was supported by landmark analysis, as well as by analysis of nPSA and T(nPSA) as time-dependent covariates. A dose > or =70 Gy was associated with a lower nPSA level and longer T(nPSA) in all risk categories, and a greater dose was significantly associated with greater PSA-DFS and DMFS in multivariate analysis. Regression analysis confirmed that higher clinical stage, Gleason score, and initial PSA were associated with a greater nPSA level. Conclusion: The results of this large, multi-institutional analysis of 4833 patients have provided important evidence that nPSA and T(nPSA) after definitive external beam RT are not only predictive of a predominantly PSA endpoint (PSA-DFS), but are also predictive of distant metastasis in all clinical risk categories. Greater RT doses were associated with lower nPSA, longer T(nPSA), and improved PSA-DFS and DMFS.     

Phase 2 study of neoadjuvant docetaxel plus bevacizumab in patients with high-risk localized prostate cancer : A Prostate Cancer Clinical Trials Consortium trial

BACKGROUND:

Treatment of high‐risk localized prostate cancer remains inadequate. The authors performed a phase 2 multicenter trial of neoadjuvant docetaxel plus bevacizumab before radical prostatectomy.

METHODS:

Eligibility included any of the following: prostate‐specific antigen (PSA) >20 ng/mL or PSA velocity >2 ng/mL/y, cT3 disease, any biopsy Gleason score 8 to 10, and Gleason score 7 with T3 disease by endorectal magnetic resonance imaging (MRI) at 1.5 T. Also, those with ≥50% biopsy cores involved and either Gleason score 7, PSA >10, or cT2 disease were eligible. Patients were treated with docetaxel 70 mg/m² every 3 weeks for 6 cycles and bevacizumab 15 mg/m² every 3 weeks for 5 cycles. The primary endpoint was partial response by endorectal MRI.

RESULTS:

Forty‐one patients were treated. Median age was 55 years (range, 40‐66 years). Baseline characteristics included: median PSA, 10.1 ng/mL; cT2, 49%, cT3, 32%; and Gleason score 8 to 10, 73%. Thirty‐eight of 41 (93%) patients completed all 6 cycles. Grade ≥3 adverse events were rare, although 3 of 41 (7%) experienced febrile neutropenia. Twelve patients (29%; 95% confidence interval [CI], 16%‐45%) achieved a >50% reduction in tumor volume, and 9 patients (22%; 95% CI, 11%‐38%) achieved a >50% post‐treatment decline in PSA. Thirty‐seven of the 41 patients underwent radical prostatectomy; there were no complete pathologic responses.

CONCLUSIONS:

Neoadjuvant docetaxel and bevacizumab is safe, and results in reductions in both tumor volume and serum PSA, in men with high‐risk localized prostate cancer. The role of neoadjuvant chemotherapy in prostate cancer, and perioperative antiangiogenic therapy in general, requires further elucidation through ongoing and planned trials. Cancer 2012. © 2012 American Cancer Society.     

Histological diagnosis of prostate cancer in Korean men aged 70-79 years

BACKGROUND: The objective of this study was to evaluate the value of the prostate-specific antigen (PSA) in the diagnosis of prostate cancer in elderly Korean men, aged 70-79 years. METHODS: Patients with an abnormal digital rectal examination (DRE) and/or a serum PSA level greater than 2.0 ng/ml underwent a biopsy. A total of 344 men (median age 73 years) constituted the study cohort. RESULTS: Of 344 men, 163 (47.4%) were diagnosed with prostate cancer upon initial biopsy. The positive predictive value (PPV) for cancer was 48.4% for a PSA cutoff of 4 ng/ml, 65.3% for a cutoff of 10 ng/ml, and 87.0% for a cutoff of 20 ng/ml. When combined with an abnormal DRE, the predictive values for these PSA cutoffs increased to 79.3, 87.3 and 100%, respectively. When 10 ng/ml was chosen as a PSA cutoff level, about 50% of patients were found to have a Gleason score of 7 or higher. When 4 ng/ml was chosen as a PSA cutoff level, more than 50% of patients with an abnormal DRE were found to have a Gleason score of 7 or higher. CONCLUSIONS: In elderly men, more than 50% of patients are found to have cancers with a Gleason score of 7 or higher when their PSA level is greater than 10 ng/ml. This threshold may be lowered to 4 ng/ml in the presence of an abnormal DRE. Our findings provide a rationale for recommending a prostate biopsy in elderly patients with an abnormal DRE and/or an elevated serum PSA level. However, at present, it is not clear whether elderly men have better outcomes when they undergo cancer screening.