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Nat Rev Urol:手术金标准时代,局部消融治疗肾癌还有空间吗?

2017-09-20 陶白 肿瘤资讯

以肾部分切除术为代表的肾脏手术切除至今仍是肾癌治疗的金标准。随着局部消融技术的日趋完善,该疗法与手术治疗之间的关系是相互竞争还是互为补充?美国福克斯癌症中心泌尿肿瘤科Serge Ginzburg教授对此进行了一项综述,并于9月12日在线发表于《Nature Reviews Urology》上。

以肾部分切除术为代表的肾脏手术切除至今仍是肾癌治疗的金标准。随着局部消融技术的日趋完善,该疗法与手术治疗之间的关系是相互竞争还是互为补充?美国福克斯癌症中心泌尿肿瘤科Serge Ginzburg教授对此进行了一项综述,并于9月12日在线发表于《Nature Reviews Urology》上。

肾部分切除术是肾脏小肿瘤(SRM)管理中的最佳方式,局部消融治疗已经在SRM的现代管理中起到重要作用,尤其在老年患者和具有合并症的患者中。如今支持消融技术安全性和有效性的数据日趋成熟,但是这些数据都受到队列异质性、选取偏倚、缺乏长期随访等混杂因素的影响;影像导航系统和消融后的监测方案各具差异,并因此未达成共识;SRM活检的重要性、活检的最佳时机、使用的活检类型、活检在治疗选择中的作用等,仍具争议。由于主动监测的安全性数据和微创肾部分切除术经验越来越多,局部消融治疗在SRM患者治疗中的作用需要继续予以评估。

消融方法

最常见的形式包括冷冻消融和射频消融,而微波消融和高强度聚焦超声(HIFU)正成为组织消融技术。通常,消融方法最常见的有数种。一种完全体外方法的创伤最小,但只有使用HIFU最为可能。其他消融方法为经皮、腹腔镜下或开放式。虽然经皮途径是在镇静下进行的,但是多数需要全麻,并且为了确保精确定位,通常需要影像导航系统。更具侵袭性的方法可使病变部位直接可视化,可操控性强,避免邻近器官被消融损伤。避免周围器官损伤的技术已经发生了演变,包括患者摆位、生理盐水注射,使邻近器官远离消融部位。这些先进的操作方法需要相当的专业知识,其成功高度依赖术者。

历史上,冷冻消融多数通过腹腔镜途径进行(65%),而射频消融多数通过经皮途径使用(94%)。一般来说,由于泌尿科医师经常治疗前列腺癌,因此对冷冻消融技术最熟悉。相反,放射科医生由于对使用经皮射频消融治疗肝、骨和肺病具有经验,因此他们偏好经皮射频消融。对于肾癌的治疗,腹腔镜下冷冻消融可使外科医生直接移动和保护覆盖在靶病变上面的结构,如血管、神经和肌肉。腹腔镜下冷冻消融期间,医生也可以将大型冷冻探针(直径高达5.0mm)置于大肿瘤中,从而形成更大和更冷的冰球。腹腔镜下冷冻消融的住院日为2.4天,而经皮冷冻消融可在门诊进行。总之,与腹腔镜途径相比,经皮途径的创伤更小,康复更快,手术相关的并发症更少。

患者选择

国际上,有多个专业学会指南,将消融疗法视为SRM的合法治疗方案,如美国泌尿学会(AUA)、欧洲泌尿科学会。之前,消融技术一直是以下SRM患者的治疗选择:具有多个并发症的老年患者、肾功能受损的患者、肾部分切除术不可行的患者。由于消融治疗可以减少缺血时间,并技术上比摘除术更容易,遗传性肾癌综合征(例如冯·希佩尔·林道病)患者多发性肾肿瘤也可考虑消融治疗。然而,由于消融治疗造成切除后的组织变化,可使将来的保留肾单位手术(NSS)更具挑战性。

一项2016年对pT1a期SRM的美国患者数据进行的分析显示,79%的患者使用了肾部分切除术,21%的患者使用了消融技术。年龄增长、合并症和肾损伤都与消融技术的使用相关。另一项对pT1期肾细胞肾癌患者治疗方式进行评估的研究显示,单身、男性、年龄增长和肿瘤较小都为消融技术的独立预测因素。由此看出,老年和体弱的患者主要选择消融治疗。

合理使用消融治疗的共识大多缺乏。因此,学者开发了模型和评分工具融入到患者选择的决策模型中。然而,各种模型和评分工具都具有缺陷,但共同之处为,低手术风险者适合肾部分切除术,而老年患者和具有合并症的患者及具有较高手术风险的患者趋于选择消融治疗。

一项系统回顾和Meta分析比较了手术和消融技术,结果显示,肾部分切除术比消融具有显着性高的并发症风险。消融治疗具有较低的总体(RR,1.82)、泌尿系统(RR,1.99)和非泌尿系统(RR,2.33)并发症。然而,具有较低围手术期风险和解剖学单纯性肾肿块的患者中,消融治疗和肾部分切除术间的并发症差异不再明显,两种疗法的选择取决于手术医生和患者的偏好。

肿瘤大小为治疗有效性的重要决定因素,<3cm一般与单纯消融治疗后完全肿瘤控制相关,而40%的3~5cm的肿瘤需要多种治疗手段。2016年进行的4~7cmSRM患者的回顾性配对分析显示,消融治疗的患者比肾部分切除术治疗的患者具有更高的局部复发率。并不是每个人都适合消融治疗,其禁忌症包括凝血功能障碍、腔静脉肿瘤受累、急性病、无法对影像学随访监测依从。

治疗前活检

治疗前活检是标准肾癌管理中的一部分,然而,多数计划进行消融治疗的患者在开始消融的时候才活检,这也被认为是消融治疗的标准方法,但是将近40%消融治疗的患者因遗漏或组织收集不足(如仅进行细针穿刺时)而在病灶治疗前不能进行组织取样。因此,泌尿科医生应该意识到组织芯活检的重要性。

治疗后监测

与摘除手术相反,消融治疗的成功与否并不根据组织学判断,而是根据影像学判断。然而,对此还未达成共识。2016年,国际上制定了术语和建议共识,将肿瘤持续性定义为3个月时造影成像的增强,将复发定义为消融区内或边缘出现新的增强或病灶增大。2009年的AUA指南建议,选择消融治疗的患者在消融治疗后要准备终生影像学监测,并在可能的情况下进行重复活检。2013年更新的指南推荐,肾癌患者在随访3个月、6个月和之后5年进行每年一次的基于造影的横断面成像。其中轴位CT或MRI是随访期最常使用的成像技术。

治疗安全性

消融治疗后,可出现一般和治疗特异性并发症。研究报道的并发症发生率存在差异:严重并发症范围为3.1%~7.4%,总体并发症发生率将近14%。

出血并发症最常见,包括血尿、小血肿、动静脉畸形、腹膜后大出血。一项研究显示,冷冻消融(4.9%)比其他消融治疗(射频消融为1.2%)更常发生此类并发症,这是由于冷冻消融缺乏热凝固效应,会增加探头数量和口径,在温度低的情况下加重血小板功能恶化。

比较热消融和肾部分切除术的研究显示,肾部分切除术与更多的泌尿系统并发症、输血和急性肾损伤相关,而热消融与更多的伤口和感染并发症相关。

肿瘤学结局

目前,多数消融治疗SRM的研究都是单中心的回顾性病例系列研究,因此结果须谨慎理解。这些研究关注的肿瘤学结局为无局部复发生存率、无转移生存率、癌症特异性生存率和总生存率。

一项Meta分析评估了47项比较了射频消融与冷冻消融的研究,得出结论,射频消融比冷冻消融的肿瘤进展率显着性高(12.9% vs 5.2%,P<0.0001)。另一项将冷冻消融和射频消融与肾部分切除术进行比较的Meta分析显示,消融治疗的局部进展率比肾部分切除术显着性高(RR分别为7.45和18.23),但是转移进展风险相似。

一项对1424例pT1a期SRM患者进行的回顾性分析显示,肾部分切除术、射频消融和冷冻消融的3年局部复发率相似(都为98%,P=0.49),而射频消融(93%)比冷冻消融(100%,P=0.021)和肾部分切除术(99%,P=0.005)的3年无远处转移生存率显着性低。然而研究作者表示,该研究具有选择偏倚,并且消融治疗的随访期有限。一项对6项试验中的587例SRM患者进行的系统回顾和Meta分析显示,消融治疗和肾部分切除术的局部复发率(3.6% vs 3.6%;P=0.79)和5年无疾病生存率(HR,1.04;P=0.92)相似。

比较无转移生存率和总生存率的高质量研究缺乏。一项回顾性分析显示,肾部分切除术、经皮射频消融和经皮冷冻消融的3年无远处转移生存率分别为99%、93%和100%。肾部分切除术和冷冻消融的价值比射频消融显着性高,然而,研究存在相当大的缺点。

功能结局

消融技术可保留肾实质,避免肾动脉主干阻断,因此,该技术会将肾出血最小化,并优化肾功能结局。

肾部分切除术对肾功能的影响可以评估。一项系统回顾显示,在具有双肾的患者中,肾部分切除术后患侧肾功能平均降低了20%,总体肾功能下降了10%。一项对大型单中心系列研究的回顾表示,与射频消融相比,肾部分切除术后,3期慢性肾疾病的发病率增加了将近11倍(HR,10.9;95% CI,1.36~88.7)。一项研究评估了2850例T1期肾癌患者使用消融治疗vs肾部分切除术对短期和长期肾功能的影响。结果显示,与消融治疗相比,肾部分切除术患者30天急性肾损伤发生率几乎是消融治疗者的2倍(9.4% vs 4.6%;OR,0.42;P=0.001)。然而,30天透析使用率都非常低(<2%),对长期肾功能的影响没有差异(P=0.6)。因此,在SRM患者长期肾功能保留上,肾部分切除术非劣效于消融治疗。

结论

由于具有重复性良好的肿瘤结局和长期肾功能结局,并具有长期随访数据予以支持,因此以肾部分切除术为代表的手术切除仍是SRM管理的金标准。消融治疗在SRM的管理中具有重要作用,并显示出与肾部分切除术相媲美的中期肿瘤学和肾功能结局和较少的并发症。在老年、具有合并症、具有中等或高手术风险的患者中,消融治疗比肾部分切除术具有优势。支持消融治疗安全性的数据受限于研究队列的异质性、选择偏倚、缺乏长期随访数据等的影响。因此,需要具有标准化报告、延长随访期和前瞻性试验,进一步确定消融技术在SRM临床实践中的作用。

原始出处:Serge Ginzburg, Jeffrey J. Tomaszewski, Alexander Kutikov. Focal ablation therapy for renal cancer in the era of active surveillance and minimally invasive partial nephrectomy. Nature Reviews Urology.(2017)

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    2018-05-18 医者仁心
  2. 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replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/ajNVdqHZLLCSvgHPvuQp0g9YLQuk8Dv2tO2J8cA1nBOPWOR46Rv1IMw309iaVI4zibSE52MibbXtA54h46besGYv6vpQfsUHpY9TaCKOVRmm2A/0, createdBy=14511949364, createdName=尹玉伟, createdTime=Wed Sep 20 09:12:11 CST 2017, time=2017-09-20, status=1, ipAttribution=)]
    2017-09-22 txqjm

    谢谢了.学习

    0

  4. 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replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/ajNVdqHZLLCSvgHPvuQp0g9YLQuk8Dv2tO2J8cA1nBOPWOR46Rv1IMw309iaVI4zibSE52MibbXtA54h46besGYv6vpQfsUHpY9TaCKOVRmm2A/0, createdBy=14511949364, createdName=尹玉伟, createdTime=Wed Sep 20 09:12:11 CST 2017, time=2017-09-20, status=1, ipAttribution=)]
    2017-09-21 chg122
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  6. 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replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/ajNVdqHZLLCSvgHPvuQp0g9YLQuk8Dv2tO2J8cA1nBOPWOR46Rv1IMw309iaVI4zibSE52MibbXtA54h46besGYv6vpQfsUHpY9TaCKOVRmm2A/0, createdBy=14511949364, createdName=尹玉伟, createdTime=Wed Sep 20 09:12:11 CST 2017, time=2017-09-20, status=1, ipAttribution=)]
    2017-09-21 lofter

    学习了.感谢分享

    0

  8. 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replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/ajNVdqHZLLCSvgHPvuQp0g9YLQuk8Dv2tO2J8cA1nBOPWOR46Rv1IMw309iaVI4zibSE52MibbXtA54h46besGYv6vpQfsUHpY9TaCKOVRmm2A/0, createdBy=14511949364, createdName=尹玉伟, createdTime=Wed Sep 20 09:12:11 CST 2017, time=2017-09-20, status=1, ipAttribution=)]
    2017-09-21 1e10c84am36(暂无匿称)

    文章很好.值得分享

    0

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createdTime=Thu Sep 21 15:00:00 CST 2017, time=2017-09-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1421682, encodeId=d2ce14216822d, content=<a href='/topic/show?id=4bc865819d2' target=_blank style='color:#2F92EE;'>#消融#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=77, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=65819, encryptionId=4bc865819d2, topicName=消融)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=1a193676008, createdName=xiangyuzhou972, createdTime=Thu Sep 21 15:00:00 CST 2017, time=2017-09-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1597726, encodeId=f106159e7264f, content=<a href='/topic/show?id=28986582e02' target=_blank style='color:#2F92EE;'>#消融治疗#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=53, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=65827, encryptionId=28986582e02, topicName=消融治疗)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f07818523366, createdName=zhishijing, createdTime=Thu Sep 21 15:00:00 CST 2017, time=2017-09-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=246245, encodeId=9bf324624541, content=学习了.感谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=82, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://q.qlogo.cn/qqapp/1103841572/C20CB8E4EBB36F5B821651C710BCB491/100, createdBy=18de1715848, createdName=lofter, createdTime=Thu Sep 21 07:27:34 CST 2017, time=2017-09-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=246209, encodeId=9de2246209b6, content=文章很好.值得分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=102, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzdAIB7UwTkHt6fQkBP8ictliaXtc5gCUmYdAW1sAETC2nhO3q6YjRHkUibyOCtP8ibmXNObTyd63A076/0, createdBy=d4111948983, createdName=1e10c84am36(暂无匿称), createdTime=Thu Sep 21 06:51:48 CST 2017, time=2017-09-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=245968, encodeId=11542459683d, content=学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=85, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/Q3auHgzwzM4KDsF1g1gUHzGM0LHxX5B5uhEMln8y8iagso9N4XBTQVPmHrCNoT3o8bw80Ds53TpTgcPnKUIfkyw/0, createdBy=bc101976400, createdName=suibian2007bbb, createdTime=Wed Sep 20 10:23:04 CST 2017, time=2017-09-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=245941, encodeId=8d832459416d, content=厉害厉害--学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=88, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/ajNVdqHZLLCSvgHPvuQp0g9YLQuk8Dv2tO2J8cA1nBOPWOR46Rv1IMw309iaVI4zibSE52MibbXtA54h46besGYv6vpQfsUHpY9TaCKOVRmm2A/0, createdBy=14511949364, createdName=尹玉伟, createdTime=Wed Sep 20 09:12:11 CST 2017, time=2017-09-20, status=1, ipAttribution=)]
    2017-09-20 suibian2007bbb

    学习

    0

  10. 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replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/ajNVdqHZLLCSvgHPvuQp0g9YLQuk8Dv2tO2J8cA1nBOPWOR46Rv1IMw309iaVI4zibSE52MibbXtA54h46besGYv6vpQfsUHpY9TaCKOVRmm2A/0, createdBy=14511949364, createdName=尹玉伟, createdTime=Wed Sep 20 09:12:11 CST 2017, time=2017-09-20, status=1, ipAttribution=)]
    2017-09-20 尹玉伟

    厉害厉害--学习了

    0

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