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前列腺癌治疗: 维生素D、欧米茄-3脂肪酸、番茄红素

时间:2021-03-01 15:02 阅读:436 来源:朴诺健康研究院

目录

一、引言

二、背景

三、病因和危险因素

四、前列腺癌的体征和症状

五、诊断

六、传统治疗

七、新兴的和新颖的治疗策略

八、饮食和生活方式注意事项

九、综合干预

十、参考文献


一、引言

摘要和速览

  1. 前列腺癌是一种常见的且在早期可以得到有效的治疗癌症。对许多男性来说,可能没有必要立即治疗。

  2. 该方案将帮助您了解前列腺癌的不同阶段以及可能需要的治疗方案。了解饮食和生活方式的改变以及补充剂作为前列腺癌的辅助治疗。

  3. 在临床试验中,各种番茄红素制剂和绿茶补充剂已被证明对前列腺癌患者有益。

在美国,大约有五分之一的男性会被诊断出患有前列腺癌(NCI 2017c; Pollock 2015)。虽然前列腺癌扩散到其他器官可能是致命的,但尽早发现是完全可以被治疗的(NCI 2018b; McLeod 2004)。前列腺癌常见的治疗方案是手术、放射和使用阻断激素的药物。(NCI 2018b; NCCN 2017b)。研究人员一直在努力优化这些治疗方法,改善前列腺癌男性的预后。(Ho 2017; Counago 2017; Montgomery 2016; Roth 2008; Holmboe 2000)。

近年来,前列腺癌诊断和治疗方面出现了许多医学创新。先进的成像技术,如多参数MRI使诊断更准确,治疗更精确(Ahmed 2017; Bagheri 2017)。新的血液检查为患者和医生提供了信息,以便他们更好地选择适当的治疗策略(Tosoian, Druskin 2017)。总的来说,免疫疗法是癌症治疗的一大进步,目前是前列腺癌研究的一个活跃且有希望的领域。(Bilusic 2017; Schepisi 2017)。

虽然很多讨论都集中在前列腺癌的具体治疗和诊断上,但在这种疾病的过程中,最重要的方面之一是患者参与其护理相关的决定。男性在前列腺癌的治疗中发挥积极,知情的作用非常重要(Baade 2012)。获得准确的信息对于前列腺癌的男性至关重要。一项研究发现,对自己的选择有更多了解的男性在治疗后六个月的生活质量更高(Orom 2016)。患者应该与其医疗团队密切合作,讨论关键的考虑因素,例如:

  1. 针对其疾病的程度有哪些治疗选择;

  2. 是否在早期前列腺癌中采用积极的治疗选择,例如手术或放射治疗,还是采取积极程度较低的方法(称为主动监测);

  3. 每种治疗方案的潜在风险和好处是什么?

该协议将为患者及其亲人提供有关前列腺健康决定时所需要的信息。您将了解目前发现和诊断前列腺癌的方法,以及该疾病不同阶段的治疗方案。该协议还包括许多正在研发的新的前列腺癌疗法,以及可能的辅助传统疗法的综合、自然干预措施。

该协议侧重于前列腺癌的治疗。有关预防的更多信息可以参阅前列腺癌预防协议。我们鼓励读者查看这两种协议以及其他的癌症相关协议:

  1. 癌症辅助疗法

  2. 癌症免疫疗法

  3. 放射治疗

  4. 化疗

  5. 癌症手术

  6. 癌症治疗:关键因素


二、背景

前列腺

前列腺是男性生殖系统的一部分并且是产生精液中重要液体成分的器官。前列腺液帮助精子通过女性生殖道到达卵子受精(NCCN 2016b; Schjenken 2015)。

前列腺位于膀胱正下方,包围部分尿道,即将尿液排出膀胱的管道(NCCN 2016b)。由于前列腺位于直肠附近,因此可以在直肠指诊的过程中感觉到。

前列腺需要睾酮才能正常工作(NCI 2017c)。特别是在青春期时期,睾酮及其代谢物双氢睾酮刺激前列腺生长(Wilczynski 2015)。

前列腺癌前和非癌前状况

随着男性年龄的增长,前列腺的生长可能导致尿道的阻塞或部分阻塞(NCI 2017a)。这种情况,称为良性前列腺增生(BPH),常见于在老年男性中,但并不是癌症的一种形式。前列腺炎或前列腺炎症,是另一种在年轻男性中更常见的非癌性疾病(Mayo Clinic 2016)。前列腺炎通常是由细菌感染引起的,但包括自身免疫过程在内的其他因素也可能导致前列腺炎(Mayo Clinic 2016; Vaidyanathan 2008)。

前列腺细胞可以在一种被称为前列腺上皮内瘤变(简称PIN)的情况下具有癌细胞的一些特征,这种情况是可以通过前列腺活检诊断出来(Voltaggio 2016; Packer 2016)。高级别PIN表示细胞看起来异常,被认为是癌前病变。在活检中检测到多个高级别PIN位点的男性比没有PIN位点的男性患前列腺癌的可能性高两倍多(Bjurlin 2014; Cicione 2016)。虽然估计值不同,但诊断为多部位高级别PIN后发生前列腺癌的风险可能高于30%(Cicione 2016)。

由于其癌前性质,通常建议在高级别PIN病例中进行仔细监测(Bjurlin 2014;Cicione 2016)。患有PIN的男性可能会从生活方式和饮食变化以及旨在预防癌症发展的靶向补品中受益(Cheetham 2011)。

前列腺癌

大多数前列腺癌属于腺癌(NCCN 2016b)。当正常的腺细胞癌变时,前列腺中就会出现腺癌(Packer 2016)。基因突变积累并促进前列腺细胞异常分裂,最终导致癌症的发展。随着肿瘤的进展,它会引起周围组织的改变使其更容易生长(Yu 2017; Levesque 2017)。

当肿瘤不再局限于前列腺时,它可能扩散到附近的其他组织如精囊(Small 2015)。它也可以扩散到尿道、直肠和膀胱(Zardawi 2016; Abbas 2011; Hallemeier 2010)。在晚期阶段,前列腺癌发现于淋巴结和身体远处的部分,如骨头,肺,或肝脏(Rycaj 2017; Macedo 2017)。该疾病在所有男性中进展的方式和速度都不相同(Pollard 2017;Peisch 2017)。


三、原因和危险因素

和其他癌症一样,前列腺癌的风险也随着年龄的增长而增加。40岁的男性在60岁前被诊断出患有前列腺癌的几率为2.3%。对于70岁的男性,20年内患前列腺癌风险为9.5%(CDC 2015)。

非裔美国男性比白人男性患前列腺癌的风险更高(Wells 2010; Zhang 2013)。在一项对近300万军人的研究中,非裔美国男性几乎是普通人的三倍(Wells 2010)。根据美国疾病控制和预防中心(CDC)的数据,非洲裔美国人死于前列腺癌的人数约为高加索人的两倍(CDC 2017年)。相比之下,亚裔美国人患前列腺癌的风险较低(Tran 2016; CDC 2017)。

有前列腺癌家族史的男性和有特定基因突变的男性患前列腺癌的风险增加(Helfand 2015; Chen 2017; Cheng 2017)。例如,BRCA1或BRCA2基因突变会增加前列腺癌的风险(Lecarpentier 2017)。BRCA2基因突变的男性在65岁之前患前列腺癌的可能性是常人的8倍多。BRCA2基因突变的存在则预示着有30-40%的可能会终生具有患前列腺癌风险,并且BRCA2基因突变与更具侵袭性的癌症形式相关。虽然BRCA1突变也与前列腺癌风险增加相关,但其相关性不如BRCA2突变那么强(Costa 2017; Mateo 2017)。

肥胖可能与晚期前列腺癌风险增加有关(Vidal 2017; Rundle 2017)。在一项对25000多名男性的大型前瞻性研究中,肥胖与非西班牙裔白人男性和非洲裔美国男性前列腺癌风险增加有关,但非洲裔男性的相关性高于其他种族的男性(Barrington 2015)。

饮食因素与前列腺癌风险有关。摄入更多的红肉(特别是高温烹饪的红肉)和动物脂肪与前列腺癌风险增加有关(Nelson 2014)。另一方面多项研究表明,健康饮食与降低前列腺癌风险和改善预后有关。研究表明富含植物性食物的饮食可能对前列腺癌有保护作用(Perez-Cornago, Travis 2017;Peisch 2017)。为了更全面地评估饮食对前列腺癌风险的影响,请回顾前列腺癌预防方案,特别是“饮食对前列腺癌风险和死亡率的影响”这一章节。

研究表明,吸烟是许多癌症的危险因素,包括前列腺癌(Tang 2017; Sato 2017; Jones, Joshu 2016)。吸烟者更容易被诊断出患有晚期前列腺癌(Ho 2014),在使用多西他素(泰索帝)(一种用于治疗前列腺癌的化疗药物)时出现疲劳(Bergin 2017),并且有并发症如前列腺手术后肺炎和计划外插管(Byun 2017)。

淋病(一种性传播感染)与前列腺癌风险增加有关(Lian 2015; Wang, Chung 2017; Vazquez-Salas 2016)。


四、前列腺癌的四个体征和症状

随着前列腺癌筛查测试的广泛使用,超过60%的前列腺癌患者在诊断时可能没有任何症状。相反,这种疾病的唯一表现可能是前列腺特异性抗原(PSA)水平升高。对于一些男性,可以在直肠指诊中感受到肿瘤的存在(Small 2015)。

晚期前列腺癌的男性可能有诸如排尿困难、盆腔区不适和精液中有血等症状(Mayo Clinic 2018)。扩散到其他器官的癌症会引起其他症状,如骨痛(NCI 2018b)。


五、诊断

筛选测试

PSA和直肠指诊。直到2008年,医生建议大多数50岁以上的男性每年进行前列腺癌筛查即PSA检测和直肠指诊(NCI 2017d; USPSTF 2008; NCI 2018a)。PSA是一种由前列腺细胞产生的蛋白(NCI 2018a;Malatest 2000),在前列腺癌患者中常见高水平的PSA。然而,前列腺特异性抗原水平也可能因良性前列腺疾病而升高,如前列腺炎和前列腺增生(USPSTF 2008;NCI 2018a)。

争议和新准则。前列腺癌筛查指南一直存在争议(Wilt 2015; Etzioni 2014; Payton 2012; Tabayoyong 2015)。随着越来越多的男性接受筛查,反对者们开始担心,太多的男性接受侵入性诊断后却发现自己没有患癌症(NCI 2017d;USPSTF 2008;USPSTF 2017)。第二个担忧是,在常规筛查中发现的某些癌症可能在该男子的一生中没有临床意义(Howrey 2013; Etzioni 2002; Andriole 2012)。

在2008年,美国预防服务工作队(USPSTF)建议不要对75岁以上的男性进行常规筛查(USPSTF,2008)。2012年,他们将这项建议扩大到所有年龄段的男子(Moyer,2012)。回顾2012-2016年文献的发现,PSA检测的使用有所下降,进行前列腺活检的人数也不如以前(Lee, Mallin 2017)。

随着常规筛查的减少,人们担心男性将在前列腺癌的晚期和较难治疗的阶段被诊断出来(Lee, Mallin 2017;Eapen 2017;Fleshner 2017)。USPSTF在2017年发布的最新前列腺癌筛查指南草案指出,“是否筛查前列腺癌的决定应该是一个人的决定”(Bibbins-Domingo 2017;USPSTF 2017)。这项声明强调了在前列腺癌筛查时个人和知情决策的重要性(Eapen 2017)。

新的筛查方法。PSA检测和直肠指诊已成为主要的前列腺癌筛查方法。以下描述了一些基本PSA检测的变化,以提高其有效性(Saini 2016; Hatakeyama 2017).

单个时间点的PSA水平可能不如PSA水平随时间变化而提供的信息丰富(Salman 2015; Adhyam 2012)。PSA速度衡量PSA上升的速度,PSA倍增时间衡量PSA水平上升两倍所需的时间(Ponholzer 2010; Loughlin 2014)。倍增时间和倍增速度已被初步研究用于前列腺癌诊断后的监测。这些指标可以显示肿瘤生长的速度,癌症是否已经转移,以及疾病对治疗的反应(Howard 2017; Freiberger 2017; Vickers 2014)。

部分PSA在血液中是游离的,还有一些与其他蛋白结合或复合(NCI 2018a)。标准PSA检测两种形式的PSA,而一种新的检测方法测量游离PSA,复合PSA可以通过这些值来计算(NCI 2018a; Brawer 1998; Brawer 2003)。复合PSA、游离PSA和包括两者信息的检测可能比单独PSA更准确地反映前列腺癌活动(Wang, Li 2017;Strittmatter 2011; NCI 2018a)。

PSA检测的另一个指标是着眼于PSA的前体形式,称为pro-PSA(Peyromaure 2005; Ito 2014; Ayyildiz 2014)。这种形式的PSA可能比总PSA更好地确定总PSA处于临界值的男性是否真的患有癌症(Boegemann 2016)。前列腺健康指数(PHI)是一种结合了总PSA、游离PSA和前PSA信息的检测。该检测于2012年获得美国食品和药物管理局(FDA)的批准,适用于50岁及以上、总血清PSA在4-10ng/mL和正常直肠指诊的男性,以减少不必要的前列腺活检(Loeb, Catalona 2014;Sartori 2014)。最近的一项研究发现,总PSA识别男性癌症的准确率为47%,而PHI测试的准确率为72%(Tosoian, Druskin 2017)。

虽然一些研究集中于改进PSA检测方法,而其他研究则开发了全新的检测方法。例如,对于PCA3测试,在直肠指诊后收集尿液(NCI 2018a;Martignano 2017)。尿液中的细胞检测前列腺癌特异性基因PCA3(Hessels 2003)。PCA3目前未被用作常规筛选检测。相反,对于PSA水平高但活检未发现癌症的男性,PCA3检测可以帮助确定哪些男性应进行再次活检,哪些应使用主动监测进行监测(Rubio-Briones 2017; Wang, Chen 2017; Galasso 2010)。

诊断测试

医生通过活检来诊断前列腺癌(Bjurlin 2014; NCCN 2016b; Small 2015)。活检通常是通过直肠壁来收集的。通常,至少要切除12个组织的核心部位(不同区域)以检查前列腺的所有区域(NCCN 2016b)。一些男性在前列腺活检后会出现副作用或并发症,如疼痛、感染或出血(NCCN 2016b; Bjurlin 2014; Jones, Radtke 2016)。

成像技术在活检过程中也是常用的方法(Woodrum 2017)。经直肠超声使用声波产生前列腺图像(NCI 2018b)。医生使用这些图像来确保从前列腺的目标区域获得活检样本(NCCN 2016b)。

医生也可以在经直肠超声检查的同时使用磁共振成像(MRI)(Marks 2013; Woodrum 2017; NCI 2018b; Jambor 2017)。术前进行MRI成像以评估患者患前列腺癌的风险,可能防止不必要的活组织检查(Porpiglia 2017; Ahmed 2017)。如果需要活检,这些高度敏感的MRI图像可以用于识别前列腺靶区(NCCN 2016b),提高对更危险的癌症的诊断(Bjurlin 2017)。在一项有601名计划进行前列腺活检的男性的研究中,MRI引导活检确定的高级别前列腺癌病例比传统活检方法多出30%(Meng 2016)。

预后评估

预后检测可以通过提供肿瘤侵袭性或扩散可能性,来帮助指导治疗选择(Terada 2017)。活检或手术中获得的组织由病理学家分析,评估细胞的特征并确定Gleason评分(Litwin 2017)。几十年来,Gleason评分系统一直被用于显示肿瘤的侵袭性,并指导治疗选择(Chen 2016; Slager 2003; Wright 2009; Humphrey 2004)。

格里森分数

格里森分数是一种已建立的肿瘤分级系统,在治疗选择中起着重要作用。为了确定格里森分数,病理学家首先在显微镜下分析活检或手术样本中的肿瘤细胞,以确定它们与正常细胞的区别,并将其表达为1到5之间的数字(NCI 2018b)。较低的数字表明细胞的特征更接近正常细胞,较高的数字表明细胞具有更多的癌变特征。病理学家给组成肿瘤大部分的两个区域分配一个编号或分级。这两个数字的总和叫做格里森分数。Gleason评分范围为2-10分(尽管临床上仅报道格里森分数为6-10分)(NCCN 2016c;ACS 2017)。此外,通常还提供单个数字(如3+4=7)。首先列出的数字是肿瘤最常见的分级(ACS 2017)。

格里森分数6分或更低得分的肿瘤可能生长缓慢,可能不需要立即进行侵袭性治疗(NCCN 2016b)。格里森分数较高的肿瘤患者预后较差,可能会从更积极的治疗计划中受益(NCCN 2017b)。2014年,针对格里森评分的患者分组发布了新指南(Gordetsky 2016; Epstein 2017):

  1. 等级1=格里森分数≤6

  2. 等级2=格里森分数3+4=7

  3. 等级3=格里森分数4+3=7

  4. 等级4=格里森分数8

  5. 等级5=格里森分数9和10

这种新的分组系统在一项对2万多名接受根治性前列腺切除术的男性的研究中得到验证。仅用PSA水平作为复发的衡量标准,1组、2组、3组、4组和5组男性无复发的5年生存率分别为96%、88%、63%、48%和26%(Epstein 2016)。

一种常用的分期系统称为TNM系统。“T”部分描述了肿瘤在前列腺内和周围的生长情况;“N”表明癌症是否已扩散到淋巴结;“M”表示肿瘤是否已转移(NCCN 2016b; Small 2015)。

在被诊断出患有前列腺癌后,患者通常会接受进一步检查,以确定癌症是否扩散到淋巴结和其他器官(即评估他们的TNM状态)(Bhindi 2017; Rodgers 2017)。选择哪种类型的附加检查取决于每个人的临床状况。PSA值较高或格里森分数较高或肿瘤较大的男性可能需要额外的影像学检查,例如使用锝99m进行骨扫描、骨盆计算机断层扫描(CT)或盆腔MRI检查肿瘤扩散(NCCN 2016b)。PSA在10-20ng/mL以上的男性常被建议进行锝-99m骨扫描。美国放射学院已经根据诸如“T”期,格里森评分,PSA水平和活检细胞核阳性数量等变量制定了指南,以帮助指导前列腺癌男性影像学检查的选择(National Guideline 2016).

MRI和CT扫描的一个弊端是,它们不能准确识别疾病的范围,这可能导致治疗过程欠佳。多参数MRI和复杂类型的正电子发射断层扫描(PET)扫描等技术的发展扩大了医生在前列腺癌评估的方法(Bednarova 2017;Fulgham 2017)。这些检测的结果可用于评估癌症分期和指导治疗方案(NCCN 2017b; NCCN 2016b; Bhindi 2017; Rodgers 2017)。其他结合PET和MRI技术的技术已经被研究;这种新模式可能在不久的将来改善治疗方案(Eiber 2013)。然而,如前所述,在决定哪种检测方法是最佳的时候,必须考虑每个患者的临床状况和独特情况。

重要的是,考虑到可用于研究前列腺癌程度的方法很多,因此对每个病人仔细评估是很重要的。一些有经验的医生指出,在评估男性临床状态时缺乏对细节的关注可能会导致TNM分期不准确,从而导致治疗效果不佳。处于前列腺癌诊断和分期阶段的男性应该向他们的医疗团队咨询很多问题,并确保他们收集到足够的信息来仔细制定他们的治疗方案。

Nomogram是一种结合了大量患者的可用临床信息的工具,并使用数学计算来评估个体发生各种事件的风险。对于前列腺癌,可能包括前列腺癌的扩散(转移)或特定治疗后的死亡率。当知识丰富的临床医生适当使用Nomogram时,可以帮助选择个体化的治疗方案(NCCN 2016b; Beauval 2017; Kim 2017; Lowrance 2009; Caras 2014)。Nomogram可以提供前列腺癌护理的许多方面的信息,包括估计活检的需要和辅助治疗的选择(Caras 2014)。然而,由于很难将这些评估标准化(即不同的Nomogram适用于不同的患者),医生可能更喜欢不同的Nomogram或对它们的解释略有不同。

多项研究表明,将多参数MRI纳入Nomogram可以提高其预测价值(Watson 2016)。虽然Nomogram在解决特定问题时可能非常有用,但它们也有一些缺点(如成本),而且也并不完全准确。此外,Nomogram只有在处理人群与Nomogram数据收集人群相似时才有效(Caras 2014)。考虑到正确使用Nomogram的复杂性,即使适当使用它们也已显示出价值,但它们可能未得到充分利用。在前列腺癌治疗计划阶段的男性应该询问他们的护理团队这些有价值的检测方法是否已经被应用到他们的护理决策过程中。


六、常规治疗

当可获得诊断和分期信息时,患者及其医疗团队可以开始考虑治疗方案(NCCN 2017b; Gillessen 2017; Small 2015)(见表1)。对于一些患有早期疾病或肿瘤且格里森分数较低的男性,可以考虑采用一种被称为积极监测的方法。在主动监测中,不进行任何治疗,并对前列腺癌进行仔细监测(Wilt 2017;Garisto 2017)。如果认为有必要进行治疗,手术和各种形式的放射线治疗是常见的初始选择(NCCN 2016b;NCCN 2017b; Small 2015)。早期治疗后病情恶化或复发的患者可能需要考虑化疗、激素治疗或免疫治疗(NCCN 2016b;Small 2015;NCCN 2017a)。

表1:基于疾病阶段和风险选择初始治疗方案

前列腺癌的类型特征治疗方案
低风险疾病

局限于前列腺的小肿瘤

格里森分数≤6分

格里森分数1组

PSA<10ng/mL

主动监测

根治性前列腺切除术

放疗(EBRT或近距离放疗)

中级风险疾病

局限于前列腺的较大肿瘤

格里森分数=7

格里森分数2-3组

PSA=10-20 ng/mL

主动监测

根治性前列腺切除术

EBRT,有时配合激素疗法

近距离放射疗法

高风险疾病

肿瘤已经生长到前列腺以外的局部结构

格里森分数≥8分

格里森分数4-5组

PSA>20ng/mL

根治性前列腺切除术,有时配合激素治疗

EBRT,通常伴有激素治疗

EBRT+近距离放疗,通常伴有激素治疗

初始治疗后病情进展通过PSA、直肠指诊或影像学检查发现疾病进展

根治性前列腺切除术,用于以前接受过放疗的患者

曾接受过手术治疗的患者接受EBRT治疗

近距离放射疗法

激素疗法

冷冻疗法

高强度聚焦超声

转移性疾病生长于前列腺以外的膀胱、直肠、淋巴结或远端器官的肿瘤

激素疗法

免疫治疗(普列威)

化疗

转移的放射治疗

治疗疼痛和其他症状

EBRT=外部光束放射治疗;PSA=前列腺特异性抗原(Small 2015;NCCN 2017b)

主动监测

手术和放射治疗是侵入性的并且有潜在的副作用和并发症(Wilt 2017; Lee 2015)。低风险前列腺癌的男性即使没有积极治疗,也很有可能在不受疾病影响的情况下生活(Wilt 2017; Hamdy 2016)。对患有低风险疾病的男性进行不必要的治疗通常被称为过度治疗(Loeb, Bjurlin 2014; Daskivich 2011)。

主动监测是定期监测PSA、直肠指诊和重复活检的方案(Garisto 2017; NCCN 2017b)。通过定期测试,可以监测患者的风险状况。如果发现任何可疑情况,可以考虑进行其他测试或主动治疗。

最近的一项研究跟踪了731名前列腺癌患者,他们被随机分配到主动监测组或手术组。近20年后,两组前列腺癌相关死亡率或因任何原因死亡率没有显著差异。与监测相比,手术与更多的不良事件相关,而监测与疾病进展治疗的可能性增加有关(Wilt 2017)。

最近的另一项试验比较了1643名低风险前列腺癌男性的主动监测、手术和放射治疗。经过平均10年的随访后,三组患者中与前列腺癌相关的死亡人数都非常少。与其他两组相比,主动监测组中转移更为常见,但仍很少(约6%)(Hamdy 2016)。

受到积极监视的患者可能会受益于实施与前列腺健康相关的饮食和生活方式。例如,健康饮食和运动都可以降低主动监测期间疾病进展的风险(Galvao 2016)。诸如欧米伽-3脂肪酸和维生素D这样的补充剂可能也有帮助(Marshall 2012;Moreel 2014)。此外,新的分子检测,如Oncotype Dx和Promark,可以帮助患者及其医疗团队在选择主动监测时更有信心(Albala 2016;Ross 2016)。(见本议定的新兴和新颖的战略部分)。

决定新诊断前列腺癌的治疗方案

当男性首次被诊断出患有前列腺癌时,他们和他们的医疗团队一起面临着决定哪种初始治疗方法适合他们。患者的风险群体在这项决定中扮演着重要角色(Small 2015; NCCN 2017b)。

但是,对于两个或更多治疗方案都合适的男性患者呢?一些研究表明,患者的治疗偏好可能会因医生的建议而改变(Scherr 2017)。这表明在决定过程中与多类型的前列腺癌专家交谈是有价值的。不做手术的放射肿瘤学家和泌尿科医生(外科医生)可能会以不同的方式提出治疗方案(Kim 2014; Jang 2010)。

患者在与医疗团队会面时,可以通过提出问题来实现对治疗预期的实际规划。缺乏完整的信息往往导致男性低估主动监测的预期寿命,并高估手术或放射治疗的的预期寿命增长效果(Xu 2016)。患者与他们的医疗团队讨论了所有治疗方案的风险和好处后,往往会对他们的最终决定更满意(Davison 2003; Holmes 2017)。

在线资源查询和宣传团队还可以帮助男性保持参与和知情权。一些专门设计的决策辅助工具能够支持治疗过程中的患者(Gorawara-Bhat 2017; Christie 2015);和使用这些工具的男性能够更好地提出有关其医疗团队推荐的治疗的关键问题((Holmes-Rovner 2017; Jones, Hollen 2016)。

根治性前列腺切除术

前列腺癌的一个常见治疗方案选择是一种叫做激进前列腺切除术的手术(NCCN 2016b)。根治性前列腺切除术主要用于被认为局限于前列腺癌症上(NCCN 2017b)。根据疾病预防控制中心的数据,2010年美国进行了大约138,000次根治性前列腺切除术(CDC 2010)。

在手术过程中,前列腺连同精囊和受影响其他区域织组一起被移除( NCCN 2016b ;NCI 2018b)。在最常见的前列腺切除术,称为耻骨后前列腺切除术,必要时可以切除淋巴结,如果不受癌症影响,勃起所需的神经可以被保留((NCI 2018b; NCCN 2016b; Tosoian 2012; Masterson 2006; Goyal 2007)。

前列腺切除术也可在腹腔镜下进行,以缩短恢复时间。在这个过程中,手术工具通过几个小切口插入。腹腔镜手术使用机械臂进行非常仔细的切割,从而减少损害健康组织的风险(NCCN 2016b;Ku 2017)。一项研究报告称,机器人辅助手术在预防PSA水平升高(可能提示复发)方面比没有辅助的腹腔镜手术更有效(Lee,Seo 2017)。

大多数男性在手术后会出现短期尿失禁或性功能障碍(NCCN 2016b)。外科手术技术的改进可以减少长期并发症的男性人数(Small 2015; Wallis 2017)。长期问题的风险因个人特征、癌症程度和外科医生的技能而有很大差异 (Goldenberg 2017)。 例如,老年患者或那些神经受到癌症影响的患者更有可能在手术后经历长期的勃起问题(NCCN 2016b)。

放射治疗

前列腺癌尚未扩散到周围组织的男性通常接受放射治疗。 对于复发性疾病和已扩散到淋巴结的疾病,放射治疗也是一种有价值的工具(Small 2015; NCCN 2017b; NCCN 2016b)。辐射会破坏癌细胞,但也可能导致对附近健康细胞造成损害(NCI 2010)。

外束放射治疗使用机器将光子束传送到前列腺(NCCN 2016b)。使用数字成像(NCI 2018b)对癌细胞进行仔细定位。调强放射治疗是一种先进的辐射形式,它从不同角度使用许被精心计算的剂量。这种方法减少了到达正常器官和组织的辐射剂量。调强放射治疗

已成为前列腺癌放射治疗的标准模式(Moon 2017)。

体部立体定向放射治疗是近年来用于治疗局部前列腺癌的男性的一种调强放射疗法。这种方法的一个优点是,大约5次就诊即可完成治疗(NCCN 2016b; Koskela 2017)。虽然这种方法是治疗前列腺癌的一种安全有效的方法,但目前正在进行的实验是将试验将体部立体定向放射治疗与其他方法进行比较(Kishan 2017;Kim 2016)。

调强放射治疗使用光子束照射前列腺,然而一种称为质子治疗的放射治疗则是使用质子束(NCCN 2016b)。质子束在一定深度释放出一定剂量的辐射。这可能允许使用更高剂量的辐射,而不会对膀胱和直肠等附近器官造成副作用(Moon 2017)。最近的一项研究招募了1375名接受质子治疗的患者,研究发现,治疗5年后,低、中、高风险患者的PSA水平分别为99%、91%和86% (Takagi 2017)。尽管这种方法很有希望,但需要将这种方法与调强放射治疗进行长期的比较研究(Magnuson 2017;月球2017)。

近距放射治疗是患有早期前列腺癌患者的另一种选择(NCCN 2017b)。使用的是一种被称为粒子的辐射发射装置,种子大约有一粒米那么大。使用成像技术引导放置,40到100个粒子被永久或暂时植入前列腺内。由于辐射直接进入肿瘤,辐射剂量可能很高,但对健康组织的风险极小(NCCN 2016b;斯蒂什2017年)。对于高风险癌症患者,近距放射治疗可与外照射放疗和激素治疗相结合(NCCN 2017b;汉农-利维2017年)。

放射治疗可引起短期和长期泌尿、肠道和性功能症状(Lee 2015)。外照射放疗也可能导致皮肤损伤(NCCN 2016b)。综合分析许多研究的数据发现,与接受手术治疗的患者相比,接受放射治疗的患者更有可能出现肠道症状,但出现泌尿或性功能问题的可能性较小(Lardas,2017; Wallis 2017)。新的设备,如SpaceOAR水凝胶系统,在放射治疗期间在前列腺和直肠之间形成了一个空间,这个空间可以增加健康组织的保护(Hamstra 2017; Wolf 2015; Augmenix 2017)。

有关更多一般信息,请参阅癌症放射治疗方案。

冷冻疗法

冷冻疗法,也被称为冷冻手术或冷冻消融,是一种较新的治疗方法,在这种方法中,氩气通过非常薄的针进入前列腺冷冻肿瘤(NCCN 2016b)。当辐射不能完全摧毁肿瘤时,冷冻疗法是一种常见的选择(NCCN 2017b); 然而,冷冻疗法作为初始治疗,其现有数据令人惊讶的(Bahn 2012; Garcia-Barreras 2017; Durand 2014)。一项研究比较了冷冻疗法和外照射疗法对新诊断出的癌症未扩散到前列腺以外的患者的疗效。两种方法在前列腺癌生存期上没有差异,并且接受冷冻治疗的患者在三年后的活检阳性率更低(Donnelly 2010)。

一位创新的医学博士Gary Onik,已经成功地用聚焦冷冻疗法治疗了局限性前列腺癌。他和他的团队采用的方法是通过一种名为“三维前列腺测绘活组织检查”的技术仔细绘制癌症的位置。然后,在肿瘤被精确定位后,对患者进行局部冷冻消融术,即对癌组织进行靶向冷冻治疗。他的团队进行的一项研究已在46名男性身上使用。

10年后的随访后经过10年的随去治疗,生化无病存活率为89%,而生化无病存活率与初始风险组没有差异。(这一点很重要,因为患有较高风险前列腺癌的男性通常患前列腺癌的复发率和死亡率较高)。与经直肠超声检查组(TRUS, 33%)相比,接受三维前列腺图谱检查组(4%)的局部复发明显较少(Onik 2014)。2016年6月,《科学家杂志?》发表了一篇题为《前列腺癌筛查和治疗的重大进展》的文章,对奥尼克博士的开创性工作发表了更全面的评论。

激素疗法

因为雄激素(男性性激素)刺激某些前列腺癌的生长,各种类型的激素疗法被用来干扰其行为(NCCN 2016b)。一些激素疗法阻止身体产生雄激素,主要是睾酮,而另一些则会阻止睾酮对癌细胞的作用(NCCN 2016b;NCI 2018b)。除早期低风险疾病外,激素治疗在前列腺癌的所有阶段都是一种有价值的工具(NCCN 2017b)。

针对促黄体生成素释放激素(LHRH)的激素疗法阻止睾丸产生睾酮。亮丙瑞林(醋酸亮丙瑞林)、戈舍瑞林(考舍林)、他铁蛋白(诺雷德)、组氨瑞林(曲普瑞林)、乙基酰胺(布舍瑞林)和地加瑞克(醋酸地加瑞克)是此类药物的例子 (NCCN 2016b;NCI 2018b)。另一种降低睾丸激素的荷尔蒙策略是使用某些形式的雌激素。手术切除睾丸(睾丸切除术)在某些情况下被用于大量的减少体内睾酮数量(NCCN 2017b)。

酮康唑(仁山利舒)是一种著名的被用于抑制包括肾上腺在内的几个部位的睾酮产生的抗真菌药物(NLM 2017;NCCN 2016a;NCI 2018b)。阿比特龙是另一种雄激素合成抑制剂,于2012年获FDA批准用于转移性去势性前列腺癌(Maluf 2012)的治疗。阿比龙加皮质类固醇泼尼松在化疗前或后使用,并可能与其他激素治疗联合使用(NCI 2013; Fizazi 2012; James 2017; Fizazi 2017).

抗雄激素阻断肿瘤细胞上的睾酮受体。比卡鲁他胺(康士得)、氟他胺、尼鲁他胺和恩杂鲁胺是抗雄激素的例子(NCCN 2016b;NCCN 2017b)。

激素治疗的副作用因患者而异,并取决于所使用的确切治疗方法(NCCN 2016b)。一般来说,激素疗法会导致勃起功能障碍、潮热、情绪变化、体重增加、肌肉萎缩、乳房生长和疲劳(NCCN 2016b; NCI 2018b; Gilbert 2017)。长期使用激素疗法会削弱患者的骨骼,增加糖尿病和心脏病的风险(NCCN 2016b; Gupta 2017; Thomsen 2017)。

及时管理黄体生成素释放激素的重要性

黄体生成素释放激素通常用于维持低水平的睾酮男性与晚期前列腺癌。然而,对近23,000名接受黄体生成素释放激素的前列腺癌患者的回顾性分析发现,27%至84%的治疗比推荐的治疗时间晚。这一结果与另一项大型研究一致,该研究也发现27%的治疗是延迟的(Twardowski 2020年)。药物通过注射或植入的方式提供,不同的配方可以持续1 - 6个月,甚至长达一年(Meani 2018; Johns Hopkins 2020)。然而这段时间过后,睾丸激素水平又开始上升。较晚注射的患者往往比按时注射的患者高出推荐的睾酮水平(Crawford 2020)。

此外,医生不太可能测量睾酮水平,他们只检查了 其中的13%, 而不是依靠 PSA 水平(83%),尽管建议使用黄体生成素释放激素的患者定期监测睾酮水平。由于证据表明维持低睾酮水平有助于前列腺癌患者的生存,因此接受黄体生成素释放激素的患者必须确保及时注射并监测睾酮水平(Crawford 2020)。

化疗

化疗是去势抵抗性转移癌的患者的另一种选择(NCCN 2017b)。多西他素是前列腺癌治疗方案中一种成熟和常用的化疗药物。关于多西他素的较新的数据表明,这种药物也可能帮助那些那些有转移或高风险非转移性癌症的患者,也就是仍然对激素治疗有反应的肿瘤患者(NCCN 2017b; Patrikidou 2017; Puente 2017; James 2016)。在该试验中,多西他赛使接受激素治疗的男性的平均生存期延长了一年多一点((Sweeney,2015)。多西他赛常见的副作用包括腹泻、恶心、呕吐和食欲不振;疲劳和弱点;低白细胞计数和发热;手脚麻木、刺痛或灼烧;脱发;口腔溃疡(NCCN 2016b; Bergin 2017; ACS 2016)。

2010年,FDA批准了化疗药物卡巴他赛(Jevtana)用于之前接受过多西他赛治疗,但癌症仍在恶化的患者上 (NCCN 2017b; Eisenberger 2017)。研究人员正在研究如何处理这种药物的副作用,优化剂量,并选择合适使用此类药物的患者(Eisenberger 2017; Patel 2017)。米托蒽醌(Novantrone)是另一种FDA批准的用于不能耐受多西他赛或卡巴他赛的患者的化疗药物(NCCN 2017b)。

有关更多一般信息,请参阅化疗方案。

免疫疗法

截至2017年底,FDA唯一批准的前列腺癌免疫疗法是自主细胞免疫治疗(NCCN 2016b; Silvestri 2016).。自主细胞免疫治疗是去势抵抗性转移癌患者的治疗选择。病人的白细胞接受一种蛋白质的治疗,这种蛋白质可以帮助白细胞识别和攻击癌细胞。细胞然后返回到患者的身体(Virgo 2017; NCI 2018b)。在一项随机对照试验中,接受自主细胞免疫治疗的男性比对照组多活了大约4个月。在最近的一项2期临床试验中,在激素治疗之前,用自主细胞免疫进行治疗时,会产生更大的抗肿瘤免疫反应(Antonarakis 2017)。这还需要进行进一步的研究,以确定这种疗法在出现去势抵抗性疾病之前是否更有效。

基于抗体的治疗

易普利姆玛(伊匹单抗), 一种针对免疫检查点 CTLA-4 的单克隆抗体, 在一项3期研究中对799名已接受化疗药物多西他赛治疗的晚期前列腺癌和骨转移患者进行了评估,参与者接受一个或多个骨转移瘤的放射治疗,然后使用伊匹单抗或安慰剂。虽然易普利姆玛在治疗后的第一年没有生存优势,但额外的随访显示易普利姆玛显著改善了长期生存率。在治疗后的第2年至第5年,依匹单抗总生存率优于安慰剂(第2年为25% vs 17%,第5年为8% vs 3%) (Fizazi 2020)。

骨转移癌的治疗

除了一般的前列腺癌治疗,如化疗和激素治疗,有几种选择专门治疗骨转移癌。外照射放疗可以针对骨骼(NCCN 2017b)。放射性药物,如镭-223,会在骨转移部位自然积聚并破坏癌细胞 (NCI 2018b; Sartor 2014)。其他药物,如狄诺塞麦(狄诺塞麦)和唑来膦酸钠(唑来膦酸注射液),可以增强受癌症影响的骨骼或通过癌症治疗而减弱的骨骼,并有助于防止骨折(Traboulsi 2017; Hegemann 2017; Israeli 2008).

参加临床试验

一些男性可能会考虑参加临床试验。许多在“新颖和新兴策略”和“综合干预”部分描述的治疗方法目前正在测试中。重要的是要认识到正在研究的治疗可能有显著的副作用或可能无效(NCI 2018b;Vieweg 2007)。不管测试的治疗是否成功,所有的临床试验都有助于为未来的病人护理提供信息。想要了解更多正在进行的临床试验的男性可以咨询他们的医疗团队。以下的在线资源可能也会有帮助:

1.国家癌症综合网:https://www.nccn.org/patients/resources/clinical_trials/find_trials.aspx 

2.国家癌症研究所:https://www.cancer.gov/about-cancer/treatment/clinical-trials/search/trial-guide

3.美国癌症协会:https://www.cancer.org/treatment/treatments-and-side-effects/clinical-trials/clinical-trials-matching-service-find-trial.html

睾酮替代疗法和前列腺癌

40岁以上的男性中,有四分之一的人缺乏睾酮。这种情况的症状和体征可能很严重,长期影响可能会使人衰弱。睾酮水平低的男性可能会经历性功能下降、抑郁、肌肉质量下降、脂肪质量增加和骨骼减弱(Golla 2017)。补充睾酮或睾酮替代疗法可以改善许多这些症状(Hackett 2016)。

从历史上看,因为担心补充睾酮可能刺激癌症生长,医学专业人士警告患有或曾经患过前列腺癌的男性不要服用。然而,目前的研究表明,通过补充睾酮恢复正常睾酮水平并不会增加前列腺癌的风险(Hackett 2016; Golla 2017; Debruyne 2017)。并且对于一些前列腺癌患者来说是安全的 (Nguyen 2016)。

一些数据表明,在主动监测期间使用睾酮可能是安全的surveillance (Golla 2017; Ory 2016; Morgentaler 2011)。此外,尽管存在争议且是初步的测试,新出现的证据表明前列腺癌治疗期间的睾酮替代可能比之前认为的问题更小, (Golla 2017)。早期的一项研究测量了积极监测但选择根治性前列腺切除术的男性的血清睾酮水平。前列腺组织检查显示,睾酮水平低的患者比活检结果显示的更有可能发生更广泛的疾病(Ferro 2017); 然而,因果关系在本研究中并不清楚。对当前研究的两项综述得出结论,在有前列腺癌病史的男性中,睾酮替代疗法改善了生活质量,并没有增加疾病进展或复发的风险(Nguyen 2016;Pastuszak 2016)。2020年发表的一项大型队列研究支持睾酮疗法的安全性。对近7万名有放疗或手术病史的非转移性前列腺癌患者的分析发现,那些随后接受睾酮治疗的患者并没有增加癌症复发或死亡的风险(Sarkar 2020)。

在男性激素恢复协议中有提供有关睾酮替代的基本信息.


七、新兴的和新颖的治疗策略

传统治疗的改进

常用的治疗,如根治性前列腺切除术,放射治疗和激素治疗正在被不断审查和完善,以提高患者的生存和生活质量(NCCN 2017b)。例如,确定最有可能从特定治疗中受益的患者群体是一个活跃的研究领域。最近的临床数据表明,根治性前列腺切除术甚至可能对患有晚期或高风险疾病的男性有帮助(Weiner 2017; Gandaglia 2017; O'Shaughnessy 2017). 手术与放射治疗联合使用可能对该患者组特别有效(Fahmy 2017;NCCN 2017b)。

研究人员也在研究各种治疗的最佳顺序和组合的新证据。如前所述,多西他赛在抗睾丸激素疗法发展之前使用可能更有效(Estevez 2016)。其他研究正在解决的问题是哪些激素疗法应该首先使用,何时开始使用(Moul 2015; Dijkstra 2016; Ho 2017; Chu 2015)。

最后,治疗前列腺癌的新药物正在研究中。新的第二代激素疗法正在开发中(Wadosky 2016;Bambury 2016;Petrunak 2017)。Seviteronel,也称为VT-464,是一种正在接受FDA的快速审批的雄激素合成抑制剂。其适用与去势抵抗性转移癌的疾病患者(Norris 2017; Teply 2016; Pharmacutical Technology 2017).。雄激素受体阻阻剂,基于SPARTAN iii期试验的良好结果,于2017年年底获得FDA优先审查。优先审查是用于男性非转移性去势性前列腺癌;FDA的意见预计将于2018年4月公布(Smith 2016;Broderick 2017)。

高强度聚焦超声

高强度聚焦超声(HIFU)正在被新诊断的前列腺癌患者和辐射后癌症复发者中进行测试(NCCN 2017b; Golbari 2017; Garcia-Barreras 2017; Crouzet 2017)。在这种方法中,超声波集中在肿瘤上,其集中能量会破坏靶向肿瘤细胞((NCCN 2016b; NCI 2018b; Kim 2008; Malietzis 2013).

HIFU目前已被FDA批准用于前列腺组织消融,但尚未被明确批准用于前列腺癌的治疗(Nelson 2015)。HIFU可能比根治性前列腺切除术产生更少的副作用,初步研究表明它在低风险患者中可能同样有效;然而,还需要更多的研究(Garcia-Barreras 2017; Kanthabalan 2017; Jones 2017; Albisinni 2017).

血管靶向光动力疗法

血管靶向光动力疗法包括注射光敏药物。将小的激光纤维插入前列腺局部激活药物,激活的药物破坏支持肿瘤的血管(NCCN 2016b)。

血管靶向光动力疗法对低风险前列腺癌男性患者的疗效。副作用很少见,光动力治疗组(约30%)两年后疾病进展的男性(约60%)少于主动监测组(约60%)(Azzouzi 2017)。此外,近一半接受光动力治疗的患者在治疗两年后获得无癌活检样本,而主动监测组只有14% (Stone 2017)。

靶向疗法

靶向疗法旨在阻止或抑制帮助癌症生长的特定分子。奥拉帕尼(Lynparza)是一种药物,可以干扰一种叫做多聚ADP核糖聚合酶(PARP)的蛋白质,帮助癌细胞修复其DNA (NCCN 2017b)。奥拉帕尼和其他PARP抑制剂可能是依赖这种DNA修复功能的男性肿瘤的有效治疗方法(Ramakrishnan Geethakumari 2017)。

在2期临床试验中,88%的肿瘤DNA修复基因缺陷患者对奥拉帕里布有反应(Mateo,2015年)。研究人员正在开发测试,以确定那些可能对奥拉帕里布和其他靶向药物有反应的患者(Goodall 2017)。2016年,FDA将奥拉帕尼授予转移性去势抵抗性前列腺癌“突破性疗法”称号,确保其快速获批(Ramakrishnan Geethakumari 2017;Helleday 2016)。

另一种新兴的治疗以高度集中于前列腺癌细胞表面的前列腺特异性膜抗原(PSMA)为靶点。被称为PSMA配体的制剂结合PSMA并携带放射性物质来破坏前列腺癌细胞(Eiber 2017;Kulkarni 2016)。

在最近的一项研究中,145名晚期前列腺癌患者接受了PSMA配体治疗。45%的患者PSA水平至少降低了50% (Rahbar 2017)。另外两项研究发现,在接受PSA指导放疗后,约80-90%的患者PSA水平下降(Baum 2016;布劳尔2017)。

免疫疗法

免疫疗法,一种利用患者自身免疫系统对抗癌症的方法,被美国临床肿瘤学协会在2016年和2017年评为“年度癌症突破奖(Madan, Gulley 2017; Rijnders 2017; Burstein 2017; Dizon 2016)。自主细胞免疫治疗是FDA批准的首批免疫疗法之一(Madan, Gulley 2017)。

癌症疫苗将一种癌症特异性蛋白质输送到身体,并引导免疫系统指向含有这种蛋白质的目标细胞(Sayour 2017)。一种为前列腺癌开发的疫苗名为PROSTVAC,旨在触发免疫系统攻击表面有PSA的细胞(Mandl 2014;DiPaola 2015)。PROSTVAC与其他抗癌药物联合应用的一二期临床试验正在进行中,截至2018年初。这些试验的结果将有助于建立PROSTVAC治疗前列腺癌的效用(Madan 2017; Fong 2017; Gulley 2017)。其他几种疫苗方法目前也正在进行早期临床试验(Lilleby 2017; Heery 2016; Yoshimura 2016).

检查点抑制剂是另一类免疫治疗药物。这些药物是针对免疫检查点蛋白的发现而开发的,肿瘤细胞利用免疫检查点蛋白使免疫细胞失活(Azoury 2015; Dyck 2017)。检查点抑制剂干预这一过程,允许患者的免疫系统继续对抗肿瘤(Rijnders 2017; Madan, Gulley 2017; Popovic 2017)。在一项测试检查点抑制剂派姆单抗 (Keytruda)用于转移性去势性前列腺癌患者的小型研究中,10例患者中有3例PSA水平急剧下降(Graff 2016)。同样显著的反应,对检查点抑制剂纳武利尤单抗(纳武单抗)和易普利姆玛(伊匹单抗)已描述在案例报告中(Basnet 2017; Cabel 2017)。其他临床试验将有助于确定哪些患者最有可能受益于检查点抑制剂免疫疗法(Popovic 2017)。

嵌合抗原受体T细胞包括提取患者的T细胞,通过基因工程使T细胞产生受体,引导它们到达癌细胞,并将这些CAR - T细胞返回到患者体内(NCI 2017b)。在一期临床试验中,5例接受CAR - t细胞治疗的患者中有2例PSA水平降低了50%和70% (Junghans 2016)。CAR - t细胞治疗前列腺癌动物模型的研究结果为进一步的研究奠定了基础(Kloss 2013; Gade 2005; Ma 2014; Zuccolotto 2014).

更多信息请参阅癌症免疫治疗方案。

筛查、诊断和预后测试

许多轻度或中度PSA水平较高的男性在活检中没有发现癌症,或者没有需要治疗的恶性肿瘤(Thompson 2004; Saini 2016)。一些新的检测方法正在开发中,以帮助PSA水平中度升高的男性决定是否进行活检(Dani 2017; Carlsson 2017)。一种名为4Kscore的复合测试使用血液中四种不同蛋白质的测量值以及患者的临床信息来预测癌症在未来15-20年内扩散的可能性(Punnen 2015;Zappala 2017;Stattin 2015)。一项对已发表数据的荟萃分析得出结论,该测试的诊断准确性与FDA批准的前列腺健康指数相似(Prostate Health Index, Russo 2017)。

直肠指诊后收集的尿液中细胞的遗传标记可能是预测癌症侵袭性的有用指标(martingnano 2017)。在一项有1077名参与者参加的试验中,与单独PSA检测相比,联合检测基因标记物TMPRSS2:ERG和PCA3提高了识别侵袭性疾病低风险男性的能力(Sanda 2017)。研究人员检查了905名前列腺癌患者尿液样本中的基因标记物,发现了另外两个标记物(HOXC6和DLX1 mRNA水平),可以帮助识别高级别癌症患者 (Van Neste 2016)。这些基因检测有朝一日可能在避免不必要的活组织检查方面发挥作用(Martignano 2017)。

新的检测方法也正在开发中,以分析通过活组织检查获得的组织。在显微镜下,这个组织可能看起来很健康,但某些分子的变化可能表明活检针漏掉了附近的癌症。ConfirmMdx((Stewart 2013; Partin 2016)和前列腺核心有丝分裂试验(PCMT) ((Robinson 2010; Legisi 2016)是商业上可用的组织测试的两个例子。这些检测结果呈阴性的患者可以选择更少或更少的重复活检(Wojno 2014;Legisi 2016)。

通过活组织检查或手术获得的前列腺组织可以通过新的检测方法进行分析,这可能提供癌症治疗力度的信息:

  1. 对2000多名患者进行了诊断,并可能预测转移的风险((Nguyen 2017; Spratt 2017).

  2. 安可待前列腺癌分析可能为临床低风险疾病的男性提供肿瘤攻击性信息,面临主动监测或治疗之间的选择(Brand 2016)。

  3. Prolaris 和 Promark 可能通过识别不太可能从更根治性的治疗中获益的男性来帮助防止过度治疗(Cuzick 2015; Tosoian, Chappidi 2017; Koch 2016; Blume-Jensen 2015; Peabody 2017)。

尽管这些测试对符合条件的患者是可行的,并由医疗保险覆盖,但仍需要长期和随机试验来确认和比较其价值((McMahon 2017; Metmark Genetics 2016)。

影像学的发展可以改善诊断和预后评估。正电子发射断层摄影术,或称PET,通过测量葡萄糖代谢和血液流动等过程,提供关于组织和器官如何运作的信息。PET扫描使用与癌症相关的被称为示踪剂的分子(Bednarova 2017)。研究人员正在努力了解使用各种示踪剂的PET扫描结果如何能够告知并改善治疗决策(Dietlein 2017;Nanni 2016)。

重新利用现有药物

一些被批准用于治疗其他疾病的药物可能对治疗前列腺癌有用。很多支持这些药物潜在益处的证据来自观察而不是临床试验;然而,一些对照试验正在进行或正在计划中。这些试验的完成将有助于澄清这些重新使用的药物在前列腺癌治疗中是否有作用。

他汀类药物是一种降低胆固醇的药物。在患有前列腺癌的男性中,胆固醇水平高的人更有可能患高级别和转移性前列腺癌(Schnoeller 2017;Thysell 2010)。此外,使用他汀类药物控制胆固醇的男性发生晚期前列腺癌的风险较低,前列腺癌生存率较高(Alfaqih 2017)。他汀类药物对抗前列腺癌的几种机制已被提出,包括前列腺肿瘤中胆固醇信号通路的调节(胆固醇是雄激素的前体,因此他汀类药物可能降低前列腺癌细胞中的雄激素生物利用度)。他汀类药物也可能影响参与细胞迁移和肿瘤进展的酶。还需要进行随机对照试验,以确定将他汀类药物添加到前列腺癌治疗中是否会带来更好的疗效(Mucci 2017)。

初步数据表明阿司匹林可以减少前列腺癌复发(Smith 2017),前列腺癌相关死亡(Jacobs 2014),或因任何原因死亡(Zhou 2017)。ADD-ASPIRIN试验正在招募2000多名前列腺癌患者,以进一步测试阿司匹林能否预防癌症复发(Coyle 2016)。

糖尿病药物二甲双胍可能会减缓前列腺癌的生长(Whitburn 2017;Sarmento-Cabral 2017)。二甲双胍已被证明可增强激素治疗和放射治疗的能力,以破坏实验室中的前列腺癌细胞和小鼠中的前列腺肿瘤(Colquhoun 2012; Whitburn 2017; Zhang 2014; Liu 2017)。在一项针对44名转移性前列腺癌男性的研究中,二甲双胍(1000mg,每日两次)稳定了病情,并使大量参与者的PSA延长了一倍时间(Rothermundt 2014)。


八、饮食和生活方式注意事项

除了这里提供的信息外,读者还应该回顾前列腺癌预防方案,因为它包含了关于饮食和生活方式因素在预防前列腺癌中的潜在作用的额外信息。

运动和体重

定期锻炼和保持健康的体重与前列腺癌患者更好的预后和生活质量有关(Peisch 2017)。较高的身体质量指数(BMI)与前列腺癌的风险增加有关(Xie,Zhang 2017)。在一次大型观察性试验中,5,158名前列腺癌患者被跟踪了几十年。在这项研究中,长期体重增加超过30磅与非吸烟者前列腺癌相关死亡风险增加约60%有关(Dickerman 2017;Perez-Cornago, Appleby 2017)。

一项对来自32个临床试验的1199名参与者数据的荟萃分析得出结论,阻力运动可以抵消与前列腺癌及其治疗相关的肌肉质量和力量损失(Keilani 2017)。另一项荟萃分析结合了来自16个随机对照试验的1574名参与者的数据,发现锻炼提高了生活质量,减少了由前列腺癌引起的疲劳(Bourke 2016)。在一项针对25名患者的研究中,健康水平的提高与PSA水平的缓慢上升有关(Hvid 2016)。需要更多的研究来解决运动项目是否可以减缓疾病进展和提高生存率(Hart 2017)。

运动可能对正在接受激素治疗的病人特别有帮助。meta分析显示,锻炼可以改善激素治疗的一些负面副作用,包括肌肉无力、疲劳、体重增加和性功能障碍(Yunfeng 2017; Baguley 2017)。一项研究的结果表明,在接受激素治疗的患者中,疲劳程度最高的人最有可能从开始锻炼项目中获益(Taaffe 2017)。

饮食

新出现的证据表明,水果、蔬菜和全谷物的饮食可能有助于降低前列腺癌的风险,改善前列腺癌患者的预后和生活质量((Carmody 2008; Nguyen 2006; Saxe 2001)。此外,初步证据表明,特定食物,如番茄酱、十字花科蔬菜、橄榄油、坚果、鱼和咖啡,可能与前列腺癌进展的风险较低有关(Peisch 2017)。

地中海饮食富含抗癌植物营养素,主要来自水果、蔬菜、全谷物和橄榄油,并与降低前列腺癌和前列腺癌相关死亡风险有关(Capurso,2017)。在一项研究中,摄入最多25%十字花科蔬菜的男性,如花椰菜、卷心菜和花椰菜,与摄入最少25%的男性相比,前列腺癌进展的风险降低了60% (Richman 2012;Kirsh 2007)。人们还注意到,通常较高的水果和蔬菜摄入量与前列腺癌生存率增加之间存在关联(Taborelli 2017)。

饱和脂肪、肉类和奶制品可能会促进前列腺癌的发展和进展(Peisch 2017)。一项研究指出,患有局限性前列腺癌的瑞典男性,如果每天至少食用三次高脂牛奶,死于该疾病的可能性要高出六倍;那些报告摄入低脂牛奶的人显示前列腺癌死亡相关的边缘降低(Downer 2017)。减少饱和脂肪和增加水果和蔬菜的摄入量已经被观察到可以防止以前治疗过前列腺癌的男性PSA水平的升高(Hebert 2012)。

多吃水果和蔬菜,少吃红肉和饱和脂肪,也可以降低前列腺癌的风险,改善一些患有前列腺癌的男性的癌症结果(Ballon-Landa 2018; Wilson 2016)。应该尽量减少摄入加工过的红肉和高温烹制的红肉 (Wilson 2016)。

饮食中欧米茄-6与欧米茄-3脂肪酸的低比例可能有利于前列腺癌患者(Apte 2013; Aronson 2011)。在一组525名患有前列腺癌的瑞典男性中,25%的参与者摄入最多的-3脂肪酸二十二碳六烯酸(DHA)和总海洋脂肪酸,他们死于前列腺癌的可能性降低了40% (Epstein 2012)。

类胡萝卜素是一种被证明对健康有益的植物色素,包括一些抗癌特性(Aghajanpour 2017)。在一项研究中,低循环类胡萝卜素水平与更高级别前列腺癌相关(Nordstrom 2016)。在一项针对复发性前列腺癌男性的研究中,他们参与了一项为期6个月的改善饮食和生活方式的项目,那些血液中类胡萝卜素水平较高的人,包括番茄红素(西红柿等食物中发现的一种红色色素),在研究结束时PSA水平较低(Antwi 2015)。煮熟的西红柿富含番茄红素(Story 2010)。较高的番茄红素摄入量与较低的前列腺癌诊断率相关,尤其是致命性癌症(Chen 2013; Zu 2014)。

多项人口研究表明,喝咖啡与降低前列腺癌,尤其是致命性前列腺癌的风险有关(Wang 2016; Pounis 2017; Wilson 2011; Peisch 2017)。在一项针对630名前列腺癌患者的研究中,那些平均每天喝4杯或更多咖啡的人比那些每天喝1杯或更少咖啡的人癌症复发的风险要低59% (Geybels 2013)。

吸烟

吸烟对被诊断出患有前列腺癌的男性可能特别有害(Peisch 2017)。与从不吸烟者相比,吸烟者更有可能被诊断出患有侵略性疾病,死于该病的可能性要高61%(Kenfield,2011)。在一项对2000多名男性的研究中,接受放射治疗时吸烟的人死于疾病的可能性是普通人的两倍多(Steinberger 2015)。其他研究发现,接受根治性前列腺切除术的吸烟者在治疗后更有可能出现PSA水平上升(Rieken 2015),并且比不吸烟者更早死亡(Curtis 2017)。吸烟者在接受多西紫杉醇化疗期间(Bergin 2017)更有可能出现治疗相关的疲劳和前列腺切除术后的并发症(Byun 2017)。


九、综合干预

维生素D

在实验室研究中,维生素D干扰多种癌症过程(Pdq Integrative 2017; Abu El Maaty 2017; Moukayed 2017)。例如,实验室数据表明维生素D可以防止癌细胞转移(Hsu 2011)。一些动物研究表明,在某些条件下,维生素D可以控制肿瘤生长(Pdq Integrative 2017;Mordan-McCombs 2010;Ajibade 2014)。此外,维生素D可以增强免疫系统,可能有助于识别和摧毁癌细胞(Pandolfi 2017)。

一些研究已经探索了维生素D是否有助于对抗人类的前列腺癌(Brandstedt 2016; Xie, Chen 2017)。在一项研究中,研究人员分析了1000名前列腺癌患者确诊前的血清维生素D水平。那些维生素D水平较高的人死于该病的可能性明显较小(Mondul 2016)。在另一项研究中,短期补充高剂量维生素D三到八周可以降低PSA水平(Wagner 2013)。作为另一项研究的一部分,52名低风险前列腺癌患者接受主动监测,每天服用4000国际单位的维生素D3,持续一年。根据活检分析,55%的男性在研究结束时前列腺癌的广泛性低于研究开始时(Marshall 2012)。补充维生素D改善了另外两项研究的PSA检测结果(Srinivas 2009;Newsom-Davis 2009)。

激素治疗可以削弱前列腺癌患者的骨骼,但补充维生素D可能有助于预防这些患者的骨折(Ottanelli 2015;Dueregger 2014)。一项研究检查了使用激素疗法的前列腺癌患者骨保存相关因素,发现服用维生素D补充剂的患者下背椎骨丢失较少(Alibhai 2013)。

绿茶

绿茶及其儿茶素,包括表儿茶素酸盐或表没食子儿茶素没食子酸酯,可能有助于对抗前列腺癌。在实验室研究中,EGCG减缓前列腺肿瘤生长并导致癌细胞死亡(Li 2014; Lin 2015)。EGCG也可能干扰前列腺癌细胞中的激素信号(Ren 2000; Siddiqui 2011; Lee 2012)。

几项人体试验表明,绿茶及其儿茶素可以预防前列腺癌,特别是在患有高等级前列腺上皮内瘤变(PIN)的男性,一种癌前病变(Pdq Integrative 2017; Jacob 2017)。在一项安慰剂对照试验中,诊断为每日服用400 mg EGCG的高等级PIN患者PSA水平下降(Kumar 2015);此外,在此剂量的EGCG补充一年后,未见毒性作用(Kumar 2016)。在一项针对高级别PIN患者的多项研究的荟萃分析中,服用绿茶儿茶素可将前列腺癌进展率从23.1%降低至7.6% (Cui 2017)。

在一项随机试验中,113名诊断为前列腺癌的男性被分配在前列腺切除术前至少三周内每天饮用6杯绿茶、红茶或水。饮用绿茶组PSA水平显著降低(Henning 2015)。在另一项试验中,人们发现每天服用800毫克EGCG的绿茶儿茶素补充剂可以降低经活组织检查确诊的前列腺癌等待前列腺切除术患者的PSA和其他一些癌症标志物的水平(McLarty 2009)。

鱼油和欧米茄-3脂肪酸

油性鱼富含欧米茄-3多不饱和脂肪酸(Ruxton,2004年)。这些脂肪酸对健康有很多益处,甚至可能减缓前列腺癌的生长(Li 2014;Berquin 2011;Aucoin 2017)。在实验室和动物研究中,omega-3脂肪酸被发现能抑制炎症,干扰肿瘤血管生长,并导致癌细胞死亡(Spencer 2009;Gu 2013)。只有鱼油作为脂肪来源的前列腺癌小鼠比喂食橄榄油、玉米油或动物脂肪的对照组小鼠活得更长(Lloyd 2013年)。进一步的分析发现,omega-3脂肪酸对老鼠体内几种类型的抗癌免疫细胞有有益的作用(Liang 2016)。

在一项包括超过29万名男性的研究中,那些在研究开始时的饮食问卷调查中报告高鱼类和高omega-3脂肪酸摄入的人在大约20年的随访中显著降低了死于前列腺癌的可能性(Bosire 2013)。在一项随机试验中,计划接受根治性前列腺切除术的男性要么吃低脂饮食并每天补充5克鱼油,要么吃传统的西方饮食。在实验室中,接触低脂加鱼油饮食的男性血液的前列腺癌细胞增长缓慢(Aronson 2011)。该研究的第二项分析发现,在低脂加鱼油饮食的患者中,促炎症标志物水平降低,预后测试得分更有利(Galet 2014)。在一项对接受积极监测的低风险前列腺癌男性的研究中,较高的肿瘤-3脂肪酸水平,特别是海洋-3脂肪酸二十碳五烯酸(EPA),与降低前列腺癌进展风险相关(Moreel 2014)。

亚麻籽是ω -3脂肪酸和纤维的植物来源,以及一类被称为木酚素的多酚类物质,它具有较弱的雌激素活性(Kajla 2015)。在一项研究中,25名等待前列腺癌手术的男性每天食用低脂饮食,并补充30克亚麻籽粉。几项试验表明,这种饮食可能减少了癌细胞的存活和增殖(Demark-Wahnefried 2001)。在一项更大的随访研究中,相似的一组患者每天吃30克亚麻籽粉,低脂饮食,低脂饮食加30克亚麻籽粉,或者对照饮食。补充亚麻籽,即使没有低脂饮食的背景,也与可能表明癌细胞分裂更慢的分子变化有关(Demark-Wahnefried 2008)。

番茄红素

如“饮食和生活方式考虑因素”一节所述,番茄红素可能有助于降低前列腺癌的风险。番茄红素有益的抗癌作用已在实验室研究中得到证实(Pdq Integrative 2017; Lin 2015)。针对人类的小型临床研究表明,补充番茄红素是安全的,并可能降低前列腺癌细胞活性(Pdq Integrative 2017;Kumar 2008)。

在一项随机对照试验中,接受手术切除睾丸治疗的男性如果每天服用4毫克补充番茄红素,PSA水平会持续下降(Ansari 2003)。另一项随机试验发现,在新诊断为局限性前列腺癌的男性中,每天服用30毫克番茄红素可以降低肿瘤生长标记物的水平(Kucuk 2001)。此外,每日食用番茄红素30毫克的中度前列腺癌男性在三周后PSA水平显著下降(Paur 2017)。

石榴

石榴含有多种对抗自由基的化合物,实验室研究表明,石榴提取物可以干扰癌细胞分裂(Pdq Integrative 2017)。在一项模拟普通成年人每天食用一到两个石榴水果的研究中,注射了前列腺癌细胞的老鼠喝的是白开水或含有石榴提取物的水。接受石榴提取物的小鼠肿瘤发病较晚,生长较慢(Malik 2005)。在一项使用高前列腺癌易感小鼠的实验研究中,相同剂量的石榴提取物可以防止转移并提高生存率(Adhami 2012)。其他一些动物研究也得出了类似的结果(Seeram 2007;Sartippour 2008;阿尔布雷特2004)。

石榴产品也在人体研究中进行了测试。在一项试验中,在接受手术或放疗后PSA水平上升并每天饮用8盎司石榴汁的男性中,PSA平均倍增时间从15个月增加到54个月。前列腺癌细胞接触到本研究中接受治疗的患者的血液后,不会迅速分裂,更容易死亡(Pantuck 2006)。一项在类似患者群体中的随机试验发现,每天剂量1克和3克石榴提取物分别延长PSA倍增时间58%和43%,这两种剂量的效果在统计学上是相同的(Paller 2013)。

十字花科蔬菜异硫氰酸酯

十字花科蔬菜,如卷心菜,花椰菜,花椰菜,羽衣甘蓝,芝麻菜,抱子甘蓝和羽衣甘蓝都含有称为芥子油苷的植物化学物质。在食物制备、咀嚼和消化过程中,硫代葡萄糖苷被分解为异硫氰酸酯(如萝卜硫素)和其他被称为吲哚的生物活性化合物(如吲哚-3-甲醇)。十字花科蔬菜分解产品有一些引人注目的抗前列腺癌特性(Novio 2016; Watson 2013)。流行病学研究发现,摄入更多十字花科蔬菜与降低前列腺癌风险之间存在相关性(Watson 2013)。20名前列腺癌患者服用富含异硫氰酸酯的西兰花提取物长达20周的小型临床研究表明,治疗期间PSA倍增时间增加(Alumkal 2015)。一项对观察性研究的荟萃分析发现,吃十字花科蔬菜最多的男性与吃十字花科蔬菜最少的男性相比,前列腺癌的相对风险降低约20% (Liu 2012)。截至2018年初撰写本文时,四项检验不同十字花科蔬菜衍生物或制剂的临床试验正在等待公布结果。

蔓越莓

蔓越莓是一种丰富的植物营养素来源,可以增强免疫系统和对抗感染,实验室和临床数据表明,蔓越莓产品可能对癌症患者有用(Weh 2016)。在几项实验室研究中,各种蔓越莓汁制剂已被证明会干扰癌细胞分裂和促进癌症生长的信号(Weh 2016;Deziel 2012;Deziel 2010)。在前列腺癌动物模型中,从蔓越莓中提取的富含原花青素的纯化物显著减缓了前列腺肿瘤的生长(Ferguson 2006)。

在一项对照临床试验中,64名计划进行根治性前列腺切除术的参与者在术前至少21天内每天服用1500毫克的蔓越莓果粉或安慰剂。服用蔓越莓组的平均PSA水平下降了22.5%,安慰剂组增加了0.9%(Student 2016)。

一些研究表明蔓越莓是否能帮助前列腺癌患者缓解泌尿系统症状。尿路感染是放疗常见的副作用(Flannigan 2014;Bonetta 2012)。蔓越莓提取物可以干扰细菌粘附尿道组织的能力(Weh 2016;Sobota 1984;Hisano 2012)。在一项对370名接受放射治疗的男性进行的随机对照试验中,那些每天接受200毫克蔓越莓提取物的人比那些接受安慰剂的人有更低的尿路感染率(8.7% vs 24.2%) (Bonetta 2012)。一项大型后续研究在一组924名参与者中证实了这些结果(Bonetta 2017)。在另一项研究中,蔓越莓提取物可以保护正在接受放射治疗的男性免受另一种常见的副作用——膀胱炎症(Hamilton 2015)。

异黄酮

大豆异黄酮,如染料木素,已被广泛研究其抗炎和雌激素调节作用(Danciu 2017)。前列腺癌细胞的实验室数据表明异黄酮可以减少炎症并干扰促进肿瘤血管生长的信号(Swami 2009;Rabiau 2010)。染料木素已被证明在实验室和动物模型中减缓前列腺肿瘤细胞增殖(Ajdzanovic 2013;王2004;El Touny 2009)。其他研究结果表明异黄酮可能使前列腺癌细胞对放射治疗更敏感(Raffoul 2007;Singh-Gupta 2010)。

在一项随机对照试验中,32名前列腺癌治疗后PSA水平上升的患者在日常饮食中加入了两片富含大豆的面包(每片提供34毫克异黄酮)或一片安慰剂面包。研究发现,在面包中加入异黄酮可以降低炎症标志物水平,抑制癌症促进免疫活动(Lesinski 2015)。在另一项包括54名计划前列腺切除术患者的随机试验中,每天接受30 mg染料木素的患者PSA水平下降了7.8%,而安慰剂组则上升了4.4% (Lazarevic 2011)。两个使用含有异黄酮的大豆饮料的小型开放试验发现,治疗后PSA水平升高的参与者PSA水平升高降低(Kwan 2010; Pendleton 2008)。

一些临床试验发现,异黄酮不会影响PSA水平或其他健康参数(deVere White 2010;Hamilton-Reeves 2013)。由于制剂、剂量、参与者特征和治疗时间的不一致,很难得出结论。需要进一步研究大豆和异黄酮对前列腺癌预后的影响。

改良柑橘果胶

果胶是一种难以消化的碳水化合物,在柑橘类水果的果皮和果肉中尤其丰富。改性柑橘果胶(MCP)是一种经过化学修饰的果胶,它被分解成更小的碳水化合物链,可以被血液吸收。研究表明,这些小块的MCP可以抑制一种叫做半乳糖凝集素-3的分子。癌细胞在转移过程中使用半乳糖凝集素-3,抑制半乳糖凝集素-3可能会阻碍癌细胞的扩散能力(Leclere 2013;Zhang 2018;Jiang 2013)。

事实上,一项使用前列腺癌大鼠模型的研究表明口服MCP可以减少转移。尽管几乎所有未经治疗的大鼠在30天后都出现了转移,但在饮用含有MCP的水的大鼠中,只有大约一半的大鼠出现了转移(Pienta 1995)。

在一项小型临床试验中,10名前列腺癌患者在接受治疗后PSA水平上升,每天服用14.4克MCP,持续12个月;PSA在10人中有7人增加了一倍(Guess 2003)。另一项公开试验测试了每天补充15克MCP对各种晚期实体癌症患者的影响。在29名完成8周补充的参与者中,20.7%的人MCP改善了生活质量和疾病稳定。一名转移性前列腺癌患者在16周时有显著的反应,PSA水平降低50%,生活质量提高,疼痛减轻(Azémar 2007)。一项正在进行的临床试验正在评估MCP对PSA水平的影响,剂量为4.8克,每天3次(Keizman 2017)。

实验室研究表明,MCP可能通过干扰细胞-细胞相互作用和粘附来阻止肿瘤的生长和扩散(Leclere 2013)。MCP和一种名为分离果胶粉的类似产品也被证明在前列腺癌细胞培养中导致细胞死亡(Jackson 2007; Yan 2010)。

姜黄素

姜黄素是一种从香料姜黄中提取的类胡萝卜素色素,具有良好的抗炎和减少氧化压力的作用。在实验室研究中,姜黄素干扰肿瘤生长信号,降低雄激素受体活性,减少PSA的产生,并减缓肿瘤生长(Li 2014; Lin 2015; Goel 2010; Rivera 2017)。在一项试验中,36名具有阉割抗性前列腺癌且PSA水平上升的患者在接受多西紫杉醇和泼尼松治疗的同时,每天给予6000 mg姜黄素。59%的参与者有PSA阳性反应(Mahammedi 2016)。另一项有85名参与者参与的研究发现,姜黄素和大豆异黄酮的组合显著降低了PSA水平高和活检阴性的男性的PSA水平(Ide 2010)。

健康的前列腺细胞通过积累锌来完成其正常的细胞功能。相反,前列腺癌细胞的锌储备已经耗尽,这使得它们更不容易细胞死亡(Costello 2016; Eidelman 2017; Franz 2013)。当前列腺癌细胞在实验室中被锌处理后,它们开始死亡(Feng 2002)。在一组超过35000名男性中,那些服用大量补充锌的人被诊断为晚期前列腺癌的可能性显著降低(Gonzalez 2009)。另一项针对525名男性的观察性研究指出,在诊断前列腺癌时,膳食中锌摄入量较高的人死于前列腺癌的风险较低(Epstein, 2011)。

褪黑素

以调节睡眠而闻名的褪黑激素,也正在成为一种有前景的抗癌药物。迄今为止的证据表明褪黑素可以干扰癌症的起始、进展和转移(Reiter 2017)。一项观察性研究发现,尿液中褪黑激素代谢产物水平较高的男性患前列腺癌的可能性显著降低,特别是晚期前列腺癌(Tai 2016)。当患有前列腺癌的啮齿动物被补充褪黑素治疗时,血管生长受到抑制,肿瘤生长更缓慢(Paroni 2014; Xi 2001; Siu 2002; Mayo 2017)。褪黑激素可能通过干扰雄激素受体信号来对抗前列腺癌(Reiter 2017)。褪黑激素也被证明降低前列腺癌细胞的葡萄糖代谢,减少癌细胞的ATP生产(ATP是关键的细胞能量储存化合物)(Hevia 2017)。褪黑激素也可能增强癌细胞对常规抗癌药物的敏感性,可能补充标准治疗(Reiter 2017)。

奶蓟草和水飞蓟素

奶蓟草(水飞蓟) 已使用数千年作为肝脏疾病的草药.。水飞蓟种子和果实中的主要活性成分之一是一种名为水飞蓟素的类黄酮复合物(Vue 2016;Abenavoli 2010;Vaknin 2008)。许多研究已经在实验室测试了水飞蓟素对患有前列腺癌的啮齿动物和前列腺癌细胞的影响。例如,水飞蓟素的一种成分被称为水飞蓟宾,它减少了肿瘤中新血管的生成,并减缓了前列腺癌小鼠的肿瘤生长(Deep 2017)。在另一项研究中,水飞蓟宾使小鼠的前列腺肿瘤对辐射的影响更敏感,但保护健康组织免受辐射损伤(Nambiar 2015)。

水飞蓟素正在进行乳腺癌(Lazzeroni 2016)、丙型肝炎(Braun 2015)和肝癌(Siegel 2014)的临床试验。在6名等待前列腺切除术的前列腺癌患者中,每天服用13克水飞蓟素制剂导致血液中水飞蓟素含量的水平升高;然而,在手术中获得的前列腺组织中水平非常低(Flaig 2010)。最近的研究探索了水飞蓟素化合物的差异,可能更有效,可能更有效地到达前列腺组织(Vue 2017; Manivannan 2017)。


本文提出了许多问题,这些问题可能会随着新数据的出现而发生变化。 我们建议的营养或治疗方案均不用于确保治愈或预防任何疾病。Piping Rock健康研究院没有对参考资料中包含的数据进行独立验证,并明确声明对文献中的任何错误不承担任何责任。


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