去势抵抗性前列腺癌中AR-V7的作用机制及其相关治疗

前列腺癌是全球男性生殖系统最常见的恶性肿瘤之一,同时也是男性肿瘤的主要死亡原因之一,近些年随着AR抑制剂阿比特龙以及恩杂鲁胺等药物的广泛应用,去势抵抗性前列腺癌(CRPC)的发病率也呈抬头趋势,本文就雄激素受体剪接变异体(AR-Vs)中的AR-V7的研究现状及其与AR抑制剂、紫杉烷类药物、AR-V7抑制剂的联系和CRPC治疗的研究新进展作一综述,为CRPC的治疗提供新的思路。     

雄激素受体剪接变异体7检测方法的研究进展

去势抵抗型前列腺癌(CRPC)治疗方法包括:以紫杉烷为基础的化疗、新型内分泌治疗、免疫疗法和镭233。目前尚无能预测CRPC患者治疗疗效并指导用药的临床生物标志物,大量研究显示雄激素受体剪接变异体(AR-V7)与阿比特龙、恩杂鲁胺耐药相关,而与紫杉烷类药物的耐药不相关,有望成为预测临床疗效、指导用药选择的一种临床实用的肿瘤标志物。然而,AR-V7的检测方法成为其应用于临床的挑战之一。本文就现有的AR-V7检测方法做一综述,并对AR-V7临床应用进行展望,以期推进AR-V7从实验室走向临床。     

陕西地区阿比特龙治疗去势抵抗型前列腺癌早期疗效及安全性的初步分析

目的分析陕西地区确诊为去势抵抗型前列腺癌(CRPC)患者行阿比特龙治疗的早期疗效及安全性,为后续治疗提供经验。方法纳入2015年12月至2016年9月陕西省西安市内五家大型三甲医院泌尿外科共计50例CRPC患者,选择使用阿比特龙联合强的松治疗,长期随访并记录治疗期间特异性前列腺抗原(PSA)、睾酮水来变化情况,每3个月复查全身骨显像、盆腔CT或MRI资料,观察并记录药物副作用,分析其中用药12周以上的30例有效病例的临床资料。结果按照PSA工作组(PSAWG)标准,30例患者PSA总体缓解率76%;按是否曾行多西他赛化疗分类,化疗失败后使用阿比特龙PSA缓解率为67%,未行化疗患者PSA缓解率达80%;按患者年龄分类,60~70、70~80、80岁PSA缓解率分别为85%、90%和61%;按患者PSA值分类,4~10、10~80、80ng/mL以上PSA缓解率分别为100%、66%和75%。阿比特龙总体耐受性良好,在我省以腹泻、水肿、低钾、肝损害常见,30例患者中3例患者出现轻度水肿,3例患者出现一过性肝功异常,1例患者出现罕见的横纹肌溶解和急性肾功损害,药物治疗后均恢复。结论陕西地区CRPC患者口服阿比特龙治疗早期疗效确切,安全性较高,可作为CRPC治疗的推荐方案之一。     

机器人辅助腹腔镜前列腺癌根治术联合新辅助内分泌治疗高危前列腺癌的临床研究

目的:探讨术前机器人辅助腹腔镜前列腺癌根治术(Robot-assisted laparoscopic radical prostatectomy,RALP)联合新辅助内分泌治疗(Neoadjuvant hormone therapy,NHT)治疗高危前列腺癌患者的临床疗效。方法:回顾性分析甘肃省人民医院泌尿外科自2018年6月-2020年12月前通过PSA、穿刺活检及MRI确诊的35例高危前列腺癌患者临床资料,其中术前行RALP+NHT治疗组25例,年龄为56~81(70.28±7.07)岁;RALP治疗组10例,年龄为49~86(69.20±8.77)岁。比较两组患者的手术时间、术中出血量、术后住院时间、术后切缘阳性率及术中和术后并发症等情况。结果:所有患者手术均获成功,无中转开放及二次手术。与RALP治疗组相比,RALP+NHT治疗组在手术时间[237.88±68.99d Vs (277±76.69)d,P=0.541]、术中出血量[(149.60±149.84)ml Vs (225±268.56)ml,P=0.266]、术后住院时间[(11±4.31) d Vs(11.7±4.86) d,P=0.402]、术后留置尿管时间[(28±6.81) d Vs (28±6.81) d,P=0.464]和术前PSA值[(49.97±32.22)ng/ml Vs (47.41±23.14)ng/ml,P=0.089]等方面差异均无统计学意义;RALP+NHT治疗组在总住院时间[(18.08±4.44)d Vs (25.5±10.82)d,P<0.005]和术后留置引流管时间[(10.12±3.36)d Vs(11.10±5.17)d,P=0.014]明显低于RALP组,差异具有统计学意义;RALP+NHT治疗组在Gleason评分(24%Vs10%)、肿瘤切缘阳性(12%Vs 20%)及并发症(4%Vs 10%)等方面下降明显。结论:术前RALP联合NHT可降低高危前列腺癌切缘阳性、改善病理分级,使高危患者受益。     

转移性去势抵抗性前列腺癌临床治疗标志物——雄激素受体剪接变异体7

随着越来越多的转移性前列腺癌患者对去势治疗抵抗,进入去势抵抗性前列腺癌(CRPC)阶段,治疗方案的合理选择及对治疗效果的预测变得越来越重要。大量研究发现雄激素受体变异体7(ARV7)参与CRPC发生与进展的过程。研究发现ARV7在CRPC中表达水平明显高于激素敏感性前列腺癌,在对阿比特龙、恩扎鲁胺治疗抵抗以及紫杉烷类药物化疗逃逸的机制中发挥了重要作用。此外,部分临床研究发现,ARV7的水平可提示不同治疗方案的预后:循环肿瘤细胞(CTC)ARV7阴性预示新型内分泌治疗与紫杉烷类化疗效果有效,而CTC ARV7阳性则预示新型内分泌治疗效果不佳。这些发现预示ARV7可成为临床医生对于CRPC治疗方案的选择以及判断预后等方面的生物标志物。     

新型雄激素合成抑制剂醋酸阿比特龙研究进展

前列腺癌是美国和欧洲男性癌症死亡的第二大原因,在中国前列腺癌发病率正逐年升高.雄激素剥夺已成为治疗晚期前列腺癌的标准.药物去势抑制睾丸生成睾酮和双氢睾酮,但肾上腺和前列腺癌组织产生的雄激素仍导致前列腺癌进展,这个阶段称为去势抵抗前列腺癌(CRPC).现在的雄激素拮抗剂已经成功地降低了前列腺特异抗原(PSA)的水平,但还不能延长患者生命.醋酸阿比特龙通过阻断对前列腺癌发展起关键作用的细胞色素P450 17α-羟化酶(CYP17)明显减少雄激素的生成,延长患者生命.随着阿比特龙和卡巴他赛等药物的应用,前列腺癌的治疗方式已经改变.这里我们提供一个有关醋酸阿比特龙作用机制和对CRPC治疗潜力的综述.     

膜联蛋白7在转移性激素敏感前列腺癌原发灶组织中的表达及其意义

目的检测膜联蛋白7(ANXA7)在转移性激素敏感前列腺癌(HSPC)原发灶组织中的表达,探讨对其预后意义。方法取转移性HSPC原发灶组织106例,免疫组化检测标本ANXA7蛋白表达,分析其表达与常见临床病理指标和疾病无进展生存时间(PFS)及总生存时间(OS)的相关性。对照组为前列腺增生20例,去势抵抗性前列腺癌(CRPC)22例。结果转移性HSPC原发灶组织ANXA7阳性表达率为50/106(47.2%),前列腺增生组织ANXA7全部阳性表达,CRPC组织为3/22(13.6%),差异比较均有显著统计学意义(P0.05)。ANXA7表达减少与T分期、N分期级别高及Gleason评分高相关,生存分析显示ANXA7表达减少与较短的PFS和OS相关,ANXA7阳性和阴性表达者PFS中位值分别为24.4月和15.5月,OS中位值分别为56.4月和36.1月。结论 ANXA7在转移性HSPC原发灶组织中表达减少,其参与疾病进展过程,表达异常往往与患者不良预后相关。     

经多西他赛化疗失败的mCRPC患者应用醋酸阿比特龙联合泼尼松龙治疗的疗效及预后因素分析

目的:研究经多西他赛化疗失败的转移性去势抵抗前列腺癌(metastatic castration-resistant prostate cancer, mCRPC)患者应用醋酸阿比特龙联合泼尼松龙治疗的疗效,以及分析影响预后的危险因素。方法:回顾性分析2017年2月—2018年2月邢台医学高等专科学校第二附属医院收治的145例mCRPC患者,经多西他赛化疗失败后均采用醋酸阿比特龙联合泼尼松龙治疗。收集患者的临床资料,研究联合治疗的效果以及预后情况,采用Cox单因素和多因素分析影响预后的危险因素。结果:145例患者中位随访时间为21.8(15.2,23.8)个月,mCRPC患者接受醋酸阿比特龙联合泼尼松龙治疗的中位前列腺特异性抗原无进展生存期(PSA PFS)为9.2(8.4,10.3)个月,中位总生存期(OS)为23.6(21.5,25.4)个月。患者主要不良反应为水钠潴留(28.97%)、低血钾(19.31%)、高血压(9.66%),总体耐受性良好,多为1～2度。Cox单因素、多因素分析结果显示,ECOG评分(0～1分vs.2分)、骨转移灶数(≤10个vs.10个)、肝转移是影响mCRPC患者接受醋酸阿比特龙联合泼尼松龙治疗预后(OS、PSA PFS)的独立危险因素(P0.05)。结论:经多西他赛化疗失败的mCRPC患者应用醋酸阿比特龙联合泼尼松龙治疗具有良好的治疗效果,ECOG评分、骨转移灶数、肝转移与联合治疗mCRPC患者的OS、PSA PFS显著相关。     

阿比特龙药物代谢在前列腺癌治疗中的意义及研究进展

正转移性去势抵抗性前列腺癌(metastatic Castration Resistant Prostate Cancer,m CRPC)是泌尿外科治疗棘手的难题。随着第二代抗雄激素药物阿比特龙(Abiraterone,Abi)的临床应用,m CRPC患者的生存时间显著延长~([1]),但Abi疗效及有效时间在个体上具有较大差异,报道显示20～40%的m CRPC患者对阿比特龙治疗无效,而几乎所有治疗有效患者后期会出现药物抵抗~([2]),研究已发现Abi代谢过程对药物自身疗效及疾病进展发挥着重要的作用~([3, 4])。     

新疆地区多中心阿比特龙和多西他赛治疗转移性去势抵抗性前列腺癌的临床疗效和安全性的对比分析

目的分析和比较新疆地区醋酸阿比特龙联合泼尼松+雄激素剥夺治疗(ADT)和多西他赛联合泼尼松+雄激素剥夺治疗(ADT)治疗转移性去势抵抗性前列腺癌(mCRPC)的临床疗效和安全性。方法回顾性分析新疆地区7家医院泌尿外科2016年6月至2018年1月收治的mCRPC患者的临床资料。阿比特龙组患者46名,多西他赛组患者48名,观察比较两组临床疗效和安全性的差异。结果中位随访时间15个月。中位影像学无进展生存期(rPFS)阿比特龙组和多西他赛组分别为15个月和11个月,中位前列腺特异性抗原无进展生存期(PSAPFS)阿比特龙组和多西他赛组分别为13个月和9个月。PSA反应率阿比特龙组63.04%,多西他赛组41.67%。在安全性方面,3～5级不良反应的比例阿比特龙组45.65%,多西他赛组47.92%。结论醋酸阿比特龙联合泼尼松+ADT治疗mCRPC相对于多西他赛联合泼尼松+ADT,改善患者rPFS、PSAPFS,提高PSA反应率。在不良反应方面,两种治疗方案无明显差异。     

Expression of Androgen Receptor Splice Variant 7 or 9 in Whole Blood Does Not Predict Response to Androgen-Axis–targeting Agents in Metastatic Castration-resistant Prostate Cancer

In 2014, a landmark study was published demonstrating that the expression of androgen receptor splice variant (AR-V) 7 was a negative predictive biomarker for response to abiraterone acetate and enzalutamide in metastatic castration-resistant prostate cancer (mCRPC) patients. However, these results were not supported by the recently reported ARMOR3-SV phase III clinical trial, which employed an identical circulating tumour cell assay to assess AR-V7 expression. Therefore, the predictive utility of AR-V7 expression in mCRPC remains uncertain, as does any potential association between other AR-Vs and treatment response. To further investigate, we designed a highly sensitive and specific whole blood assay for detecting AR-V7 and AR-V9. We then examined for a correlation between baseline AR-V7/V9 status and treatment outcome in 37 mCRPC patients commencing abiraterone or enzalutamide. Of the patients, 24% (9/37) were AR-V–positive. Notably, prostate-specific antigen (PSA) response rates did not significantly differ between AR-V–positive (6/9) and AR-V–negative (18/28) patients (66% vs 64%, p = 0.9). Likewise, median PSA progression-free survival was not significantly different between AR-V–positive and AR-V–negative patients (9.2 mo vs not reached; p = 0.9). These data, which support the findings of the pivotal ARMOR3-SV clinical trial, suggest that baseline AR-V expression does not predict outcomes in mCRPC patients receiving abiraterone or enzalutamide.

A Multicohort Open-label Phase II Trial of Bipolar Androgen Therapy in Men with Metastatic Castration-resistant Prostate Cancer (RESTORE): A Comparison of Post-abiraterone Versus Post-enzalutamide Cohorts

BackgroundCyclic high-dose testosterone injections, also known as bipolar androgen therapy (BAT), is a novel treatment strategy for patients with metastatic castration-resistant prostate cancer (mCRPC). BAT has shown clinical activity in prior studies enrolling men with mCRPC and may potentially restore sensitivity to prior androgen receptor (AR)-targeted agents.ObjectiveTo evaluate the clinical activity of BAT in patients progressing on AR-targeted therapy as well as responses to abiraterone or enzalutamide upon rechallenge after BAT.Design, setting, and participantsRESTORE is a multicohort phase II study enrolling asymptomatic mCRPC patients after abiraterone or enzalutamide at Johns Hopkins Hospital (NCT02090114). Participants (29 after abiraterone and 30 after enzalutamide) received 400 mg testosterone cypionate intramuscularly every 28 days, with ongoing luteinizing hormone-releasing hormone agonist/antagonist treatment (ie, BAT). Following progression on BAT, patients were rechallenged with their most recent AR-targeted therapy.Outcome measurements and statistical analysisCoprimary endpoints were >50% decline in PSA from baseline (PSA₅₀) responses to BAT and following AR-targeted therapy rechallenge. Outcomes in the post-abiraterone cohort are presented, as well as updated results from the post-enzalutamide cohort and an exploratory AR-V7 analysis.Results and limitationsNo statistically significant difference in PSA₅₀ response rates to BAT was observed (30% [post-enzalutamide cohort] vs 17% [post-abiraterone cohort], p = 0.4). However, PSA₅₀ responses to AR-targeted therapy rechallenge were higher in the post-enzalutamide cohort (68% vs 16%, p = 0.001). The median time from enrollment to progression following rechallenge with AR-targeted therapy (ie, progression-free survival 2; PFS2) was longer in the post-enzalutamide versus post-abiraterone patients (12.8 vs 8.1 mo, p = 0.04). Outcomes were worse in patients with detectable AR-V7 in circulating tumor cells (median PFS2: 10.3 vs 7.1 mo, p = 0.005).ConclusionsBAT shows clinical activity in mCRPC patients and may be more effective at resensitizing to enzalutamide versus abiraterone.Patient summaryBAT is well tolerated in metastatic castration-resistant prostate cancer patients. The type of prior AR-targeted therapy might affect response to BAT as well as AR-therapy rechallenge. BAT followed by AR-targeted therapy rechallenge did not improve outcomes in AR-V7–positive patients.     

Expression of AR-V7 in Circulating Tumour Cells Does Not Preclude Response to Next Generation Androgen Deprivation Therapy in Patients with Castration Resistant Prostate Cancer

The androgen receptor splice variant AR-V7 has recently been discussed as a predictive biomarker for nonresponse to next-generation androgen deprivation therapy (ADT) in patients with castration-resistant prostate cancer. However, we recently identified one patient showing a response from abiraterone despite expression of AR-V7 in his circulating tumour cells (CTC).Therefore, we precisely assessed the response in a cohort of 21 AR-V7 positive castration-resistant prostate cancer patients who had received therapy with abiraterone or enzalutamide. We detected a subgroup of six AR-V7 positive patients showing benefit from either abiraterone or enzalutamide. Their progression free survival was 26 d (censored) to 188 d. Four patients displayed a prostate-specific antigen decrease of >50%. When analysing prior therapies, we noticed that only one of the six patients had received next-generation ADT prior to CTC collection.As a result, we conclude that AR-V7 status in CTC cannot entirely predict nonresponse to next generation ADT and AR-V7-positive patients should not be systematically denied abiraterone or enzalutamide treatment, especially as effective alternative treatment options are still limited.

Novel Junction-specific and Quantifiable In Situ Detection of AR-V7 and its Clinical Correlates in Metastatic Castration-resistant Prostate Cancer

Background

Androgen receptor splice variant 7 (AR-V7) has been implicated in resistance to abiraterone and enzalutamide treatment in men with metastatic castration-resistant prostate cancer (mCRPC). Tissue- or cell-based in situ detection of AR-V7, however, has been limited by lack of specificity.

Clinical Utility of the Nuclear-localized AR-V7 Biomarker in Circulating Tumor Cells in Improving Physician Treatment Choice in Castration-resistant Prostate Cancer

BackgroundProof of the clinical utility of a biomarker is when its use informs a management decision and improves patient outcomes relative to when it is not used.ObjectiveTo model the clinical benefit of the nuclear-localized androgen receptor splice variant 7 (AR-V7) test for men with progressing metastatic castration-resistant prostate cancer (mCRPC) at the second line of therapy or greater to inform the choice of an androgen receptor signaling inhibitor (ARSI) or a taxane.Design, setting, and participantsThe study population was a cross-sectional cohort of 193 unique patients with progressing mCRPC from whom 255 samples were drawn at the time of the second line or later treatment decision who then received an ARSI or taxane, with up to 3 yr of additional follow-up Circulating tumor cells (CTCs) were identified from blood samples and tested for AR-V7. Physicians were blinded to AR-V7 status and the testing laboratory was blinded to outcomes.Outcome measurements and statistical analysesWe measured physician propensity for choosing an ARSI or taxane based on patient prognosis. We also measured overall survival (OS) adjusted for physician propensity by drug class; OS data were analyzed both without and with knowledge of nuclear-localized AR-V7 status.Results and limitationsTreating physicians had a propensity for choosing a taxane over an ARSI for patients with more advanced disease or who received an ARSI as the immediate prior therapy. After adjusting for physician propensity, discernible OS differences were not observed between taxane- and ARSI-treated patients (median 15.6 vs 14.4 mo; p =0.11). Patients with detectable nuclear-localized AR-V7 in CTCs had superior survival with taxanes over ARSIs (median 9.8 vs 5.7 mo; p = 0.041). AR-V7–negative patients had superior survival on ARSIs over taxanes (p = 0.033) but overlapping curves limit the interpretation. Mutivariable models showed a robust interaction between AR-V7 status and drug, and a lower risk of death on taxanes for AR-V7–positive men.ConclusionsUse of the nuclear-localized AR-V7 CTC test to inform treatment choice can improve patient outcomes relative to decisions based solely on standard-of-care measures.Patient summaryMen with metastatic prostate cancer who test positive for AR-V7 protein in circulating tumor cells are likely to live longer if taxane chemotherapy is used.     

前列腺液中B7-H3分子表达对t-PSA灰区内炎性PSA升高的鉴别诊断价值

目的 探讨前列腺液(EPS)中B7-H3分子对血清t-PSA灰区(4～10 ng/ml)内炎性PSA升高患者的鉴别诊断价值.方法 选择2009年12月至2010年4月收治的全部慢性前列腺炎(CP)患者和t-PSA灰区内行前列腺穿刺活检患者共116例,年龄19～80岁,平均40岁.CP 91例,年龄19～49岁,平均31岁.其中慢性细菌性前列腺炎(II型)11例、慢性炎症性非细菌前列腺炎(IIIA型)26例、慢性非炎症性非细菌前列腺炎(IIIB型)54例.t-PSA灰区内接受经直肠超声引导下前列腺穿刺活检患者25例,年龄62～80岁,平均71岁,t-PSA(7.21±2.60)ng/ml.其中穿刺病理结果阳性5例,Gleason评分6分2例、7分2例、8分1例;阴性20例,其中伴炎症细胞浸润11例.采用经直肠按摩法提取EPS.酶联免疫吸附法检测各组EPS B7-H3水平.健康男性对照11例,年龄24～46岁,平均30岁.既往无泌尿系不适症状及手术史.结果 对照组、II型组、IIIA型组、IIIB型组EPS中B7-H3水平依次为(49.81±11.54)、(19.33±13.90)、(17.67±15.76)、(25.14±13.44)ng/ml,穿刺阳性组、阴性不伴炎症组、阴性伴炎症组分别为(26.30±16.32)、(30.23±18.42)、(10.11±5.42)ng/ml.CP各组EPS B7-H3水平均低于对照组,差异有统计学意义(P＜0.01).II型组和IIIA型组间差异无统计学意义(P＞0.05),但均显著低于IIIB型组,差异有统计学意义(P＜0.05).穿刺阴性伴炎症组EPS中B7-H3水平与II型组、IIIA型组比较差异无统计学意义(P＞0.05),但显著低于穿刺阳性组及阴性不伴炎症组,差异有统计学意义(P＜0.05).EPS B7-H3表达检测在t-PSA灰区内诊断炎性PSA升高患者的ROC曲线下面积为0.883(P=0.001),当EPS B7-H3值≤16.24 ng/ml时,诊断敏感性为78.6%,特异性为81.8%.结论 EPS B7-H3表达检测可能成为t-PSA灰区内鉴别诊断炎性PSA升高的新指标,从而减少不必要的前列腺穿刺活检.

Abstract：

Objective To investigate the value of B7-H3 in expressed prostatic secretions (EPS) in differential diagnosis of patients with inflammatory elevation of PSA in t-PSA gray zone (4-10 ng/ml). Methods One hundred and sixteen patients from the ages of 19 to 80 years (mean, 40 years) were stu-died. In the group there were 91 chronic prostatitis (CP) patients (mean age 31 years, 19-49 years), including 11 chronic bacterial prostatitis (type II) patients, 26 inflammatory nonbacterial prostatitis (IIIA) patients and 54 noninflammatory nonbacterial prostatitis (IIIB) patients. Transrectal ultrsound guided prostate biopsy was performed on 25 patients (mean age 71 years, 62-80 years) with t-PSA in gray zone (7.21±2.60 ng/ml). Five had positive results, Gleason score was 6 in two cases, 7 in two cases and 8 in one case. Twenty patients had negative results, of whom 11 patients had inflammatory cell infiltration. EPS was collected by transrectal massage, and Enzyme-linked immunosorbent assays (ELISA) were performed for B7-H3 detection. In addition, 11 normal male controls with a mean age of 30 years (24-46 years) were recruited into the study. Volunteers were excluded if they had a history of genitourinary symptoms or surgery.Results The EPS B7-H3 levels of controls, II, IIIA, IIIB groups were 49.81±11.54, 19.33±13.90, 17.67±15.76, 25.14±13.44 ng/ml, respectively. The levels of EPS B7-H3 in positive biopsy, noninflammatory negative biopsy and inflammatory negative biopsy groups were 26.30±16.32, 30.23±18.42, 10.11±5.42 ng/ml, respectively. The highest levels were found in the control group (P<0.01). Compared to the IIIB, B7-H3 levels in II and IIIA groups were significantly lower (P<0.05). There was no significantly difference between II and IIIA groups (P>0.05). The EPS B7-H3 levels in the inflammatory negative biopsy group were statistically lower than in positive biopsy and noninflammatory biopsy groups (P<0.05). But no significant differences were found among inflammatory negative biopsy, II and IIIA groups (P>0.05). Receiver operating curve (AUC=0.883, P=0.001) utilizing EPS B7-H3 levels≤16.24 ng/ml identified patients with inflammatory elevation of PSA with a sensitivity of 78.6% and a specificity of 81.8% from patients with t-PSA in gray zone. Conclusion The EPS B7-H3 detection provides a new way for differential diagnosis of patients with inflammatory elevation of PSA in t-PSA gray zone resulting in a reduction of unnecessary prostate biopsy.     

^68Ga-PSMA PET-CT检查中SUVmax与前列腺癌患者临床病理特点的相关性分析

目的探讨^68Ga-PSMA PET-CT检查中前列腺局部病灶最大标准摄取值(maximum standardized uptake value,SUVmax)与前列腺癌患者临床病理特点的相关性。方法回顾性分析2016年5月至2019年8月北京大学肿瘤医院行^68Ga-PSMA PET-CT检查并行根治性前列腺切除术患者的病例资料。共31例患者。年龄(63.1±4.9)岁。体质指数(24.6±3.0)kg/m^2。血清总PSA(72.71±173.15)ng/ml。14例有基线睾酮数值,基线睾酮(4.72±1.64)ng/ml。穿刺病理Gleason评分按国际泌尿病理学会(International Society of Urological Pathology,ISUP)分级:1级5例,2级7例,3级4例,4级10例,5级5例。术前临床分期:T2a期6例,T2b期2例,T2c期17例,T3a期1例,T3b期4例,T4期1例。所有患者均行^68Ga-PSMA PET-CT检查,由2名核医学专业医生复核SUVmax。原发灶SUVmax(12.49±9.38)。分析SUVmax值与基线PSA、Gleason评分、术后病理情况的关系。结果本研究31例术后ISUP分级:1级3例,2级9例,3级4例,4级6例,5级9例。术后病理分期:T2a期1例,T2c期14例,T3a期6例,T3b期10例。术后病理诊断为切缘阳性19例,阴性12例;脉管癌栓阳性5例,阴性26例;神经侵犯阳性20例,阴性11例。D′Amico危险度分层:低危2例,中危7例,高危22例。按照PSA(≤10 ng/ml或>10 ng/ml)和Gleason评分(≤6分或>6分)分类:低PSA低Gleason评分6例,低PSA高Gleason评分5例,高PSA低Gleason评分9例,高PSA高Gleason评分11例。SUVmax与术后病理ISUP分级具有显著正相关性(r=0.434,P=0.015),与术后病理分期(r=0.232,P=209)、基线PSA(r=0.178,P=0.339)和基线睾酮(r=0.437,P=0.119)无相关性。脉管癌栓阳性组和阴性组的SUVmax分别为14.78±10.^68和8.17±2.81,差异有统计学意义(P=0.005)。病理切缘阳性组和阴性组的SUVmax分别为12.84±7.89和11.79±11.39(P=0.764),神经侵犯阳性组和阴性组的SUVmax分别为22.59±13.72和10.48±6.89(P=0.055),盆腔淋巴结阳性组和阴性组的SUVmax分别为14.50±9.64和12.13±9.32(P=0.639),D′Amico危险度低、中危组和高危组的SUVmax分别为9.39±4.60和13.^68±10.39(P=0.247),差异均无统计学意义。低PSA低Gleason组、低PSA高Gleason组、高PSA低Gleason组、高PSA高Gleason组的SUVmax分别为8.67±4.26、16.70±13.90、9.43±7.75、15.00±9.38,组间差异无统计学意义(P=0.285)。术后病理与穿刺病理ISUP分级相同者19例,SUVmax 11.92±10.61;升级者9例,SUVmax 16.01±5.40;降级者3例,SUVmax 4.98±2.11,3组差异无统计学意义(P=0.287),但升级者SUVmax显著高于降级者(P=0.007)。SUVmax对术后病理ISUP分级的诊断效能受试者工作特征(receiver operating characteristic,ROC)曲线显示,SUVmax对判断术后病理ISUP分级5级的诊断效能最大,曲线下面积0.747(P=0.033);当SUVmax≥11.34时,敏感性可达88.9%,特异性可达77.3%。结论术前^68Ga-PSMA PET-CT中前列腺局部病灶的SUVmax可辅助判断前列腺癌患者是否存在病理预后不良因素,可能具有临床指导意义。     

Nuclear-specific AR-V7 Protein Localization is Necessary to Guide Treatment Selection in Metastatic Castration-resistant Prostate Cancer

Background

Circulating tumor cells (CTCs) expressing AR-V7 protein localized to the nucleus (nuclear-specific) identify metastatic castration-resistant prostate cancer (mCRPC) patients with improved overall survival (OS) on taxane therapy relative to the androgen receptor signaling inhibitors (ARSi) abiraterone acetate, enzalutamide, and apalutamide.

前列腺特异抗原测定对女性高雄激素症的诊断价值

目的:研究前列腺特异抗原(PSA)是否可作为女性高雄激素症诊断的标志。方法:正常对照组50例,高雄激素症组45例,分别测定血清PSA、睾酮(T)、性激素结合球蛋白(SHBG)、硫酸脱氢表雄酮(DHEA-S)水平,对两组测定值进行统计学分析。结果:正常对照组血清PSA值为(3.56±0.44)pg/ml,高雄激素症组为(9.72±1.39)pg/ml,两组有显著性差异(P<0.01)。血清PSA值与T、DHEA-S值之间呈弱的正相关关系(分别为r=0.226,P<0.05;r=0.255,P<0.05);与SHBG值之间有弱负相关关系(r=-0.228,P<0.05)。结论:PSA可作为女性雄激素增高的标志物而在临床应用。     

前列腺癌肿瘤组织中E-cadherin和N-cadherin的表达及意义

目的:探讨上皮-间质转化(EMT)相关蛋白E-cadherin和N-cadherin在中低危前列腺癌和高危前列腺癌中的表达差异,以及E-cadherin和N-cadherin的表达与患者年龄、血清PSA水平、肿瘤组织Gleason评分的关系。方法:回顾性分析42例前列腺癌患者临床资料,将前列腺癌分为高危组27例和中低危组15例。免疫组化法检测两组E-cadherin和N-cadherin的表达,并比较两组有无差异;同时分析E-cadherin和N-cadherin的表达阳性率与血清PSA值、肿瘤Gleason评分及患者年龄的关系。结果:E-cadherin在中低危组的表达水平高于高危组(6.1±0.51 vs 4.2±0.37,P0.01),并且在中低危组中表达阳性率显著高于高危组(73.3%vs 25.9%,P0.01),E-cadherin在PSA20μg/L的患者中表达阳性率高于PSA≥20μg/L的患者(66.7%vs 29.6%,P0.05),在Gleason评分5~7分的患者中,其表达阳性率明显高于Gleason评分8~10分的患者(60.9%vs 21.1%,P0.05)。N-cadherin在中低危组的表达水平低于高危组(3.7±0.32 vs 7.5±0.58,P0.01),并且在中低危组中的表达阳性率低于高危组中(13.3%vs 59.3%,P0.05),在Gleason评分5~7分的患者中,其表达阳性率明显低于Gleason评分8~10分的患者(26.1%vs 63.2%,P0.05),N-cadherin在PSA20μg/L和PSA≥20μg/L的患者中表达阳性率没有差异(P0.05)。E-cadherin和N-cadherin在年龄≥70岁和70岁的患者中表达阳性率均没有明显差异(P0.05)。结论:E-cadherin和N-cadherin在高危前列腺癌和中低危前列腺癌表达阳性率及表达水平存在差异,即两者与前列腺癌的侵袭转移有关,并且E-cadherin和N-cadherin的表达可能与前列腺癌Glesaon评分、血清PSA水平有关。