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ASCO GU 研究者说丨St-Laurent教授:尿液肿瘤DNA可发现微小残留病灶,助力患者更长生存

作者:  陈梓儒   日期:2024/2/5 20:15:08  浏览量:1344

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泌尿肿瘤领域盛会ASCO-GU 2024已经在美国旧金山举行,展示了诸多创新性研究进展,探讨了泌尿男生殖系肿瘤未来的治疗方向;对于卡介苗(BCG)治疗无反应的非肌层浸润性膀胱癌(NMIBC)患者而言,仍需寻找有效工具来检测二线保膀胱治疗的复发或进展风险。会议期间,来自不列颠哥伦比亚大学的Marie-Pier St-Laurent教授介绍了利用尿液肿瘤DNA(utDNA)全基因组分析来识别微小残留病灶(MRD)及量化基因组改变的最新进展,并在接受肿瘤瞭望的采访中进行了深度分享。

编者按:泌尿肿瘤领域盛会ASCO-GU 2024已经在美国旧金山举行,展示了诸多创新性研究进展,探讨了泌尿男生殖系肿瘤未来的治疗方向;对于卡介苗(BCG)治疗无反应的非肌层浸润性膀胱癌(NMIBC)患者而言,仍需寻找有效工具来检测二线保膀胱治疗的复发或进展风险。会议期间,来自不列颠哥伦比亚大学的Marie-Pier St-Laurent教授介绍了利用尿液肿瘤DNA(utDNA)全基因组分析来识别微小残留病灶(MRD)及量化基因组改变的最新进展,并在接受肿瘤瞭望的采访中进行了深度分享。
 
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肿瘤瞭望:首先请简单介绍下您在ASCO-GU上分享的研究内容。

Marie-Pier St-Laurent教授:本次会议上的这项研究对SWOG 1605研究入组人群的utDNA进行了全基因组分析,目的是想确认utDNA是否可以预测接受阿替利珠单抗治疗的BCG无反应NMIBC患者的复发情况。研究结果显示,基线时utDNA阳性患者在12个月和18个月内复发的可能性几乎是阴性患者的3倍。研究表明,对于膀胱镜检查和细胞学检查均为阴性的患者,也可通过utDNA发现微小残留病灶(MRD)的肿瘤突变情况。这项研究可以进一步指导后续研究及临床实践,如通过膀胱活检来检测当前标准方案未发现的复发情况。
 
 
Oncology frontier:Please brief your abstract presented during ASCO GU.
 
Dr.Marie-Pier St-Laurent:Our study,derived from SWOG 1605,investigated urine tumor DNA(utDNA),aiming to determine if this test could predict recurrence in patients treated with atezolizumab for BCG-unresponsive NMIBC.Our findings revealed that patients testing positive for utDNA at baseline were almost three times more likely to experience recurrence within 12 and 18 months compared to those testing negative.Interestingly,this test helped identify minimal residual disease(MRD)in patients showing no disease via cystoscopy and cytology but having high tumor mutations in their urine.This could guide further investigations,such as bladder biopsies,to detect recurrences not identified by current standard methods.
 
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肿瘤瞭望:高危NMIBC的标准治疗是经尿道膀胱肿瘤电切术(TURBT)及术后灌注卡介苗(BCG),但近1/3的患者对BCG无应答。这部分患者的后续治疗策略有哪些?

Marie-Pier St-Laurent教授:对于BCG无反应的患者,目前的标准治疗通常包括膀胱切除术等方案。然而由于存在相关风险,许多患者会选择替代治疗方案,具体治疗选择取决于其所在国家/地区的药物可及性。尽管完全缓解率较低,但帕博利珠单抗已获得FDA批准治疗高危NMIBC并具有一定疗效;当时的研究人员并未进行前瞻性研究,但因其成本较低而经常被使用。如果患者拒绝接受膀胱切除术,则通常建议参加临床试验,以使患者拥有更多治疗选择。SWOG 1605研究表明,阿替利珠单抗治疗6个月的完全缓解率优于帕博利珠单抗,但由于试验标准等原因而未能获得FDA批准。
 
Oncology Frontier:The standard treatment for high-risk NMIBC is transurethral resection of bladder tumors(TURBT)and postoperative infusion of BCG,but nearly one-third of patients do not respond to BCG.What are the follow-up treatment strategies for these patients?
 
Dr.Marie-Pier St-Laurent:For BCG-unresponsive patients,the standard of care usually involves cystectomy.However,due to associated risks,many patients opt for alternative treatments,depending on availability in their country.Pembrolizumab has been approved and shows some response,albeit with a lower complete response rate.Researchers not studied prospectively in past,but pembrolizumab is often used due to its lower cost.If cystectomy is declined,clinical trials are recommended,offering various treatment options.Atezolizumab,as investigated in SWOG 1605,displayed better complete response at six months than pembrolizumab,but it was not approved by the FDA due to the trial’s criteria.

03
肿瘤瞭望:您在ASCO GU大会公布了atezolizumab治疗后BCG无应答患者的基因组特征,其中是否存在某些生物标志物,从而来预测疗效或筛选合适患者?

Marie-Pier St-Laurent教授:我们分析了utDNA作为潜在的生物标志物。目前尚无生物标志物能够最终显示出预测治疗反应的能力。该领域也正在积极研究各种生物标志物,包括血液中的循环肿瘤DNA(ctDNA),尽管其在NMIBC的研究并不常见。该领域正在进行的研究前景广阔,我们也期待未来能够出现良好的生物标志物,以促进患者的更好生存。
 
Oncology Frontier:You announced the genomic characteristics of BCG non-responsive patients after atezolizumab treatment at the ASCO GU conference.Are there any biomarkers that can be used to predict the efficacy or screen suitable patients?
 
Dr.Marie-Pier St-Laurent:We’ve examined urine tumor DNA as a potential biomarker.Currently,no biomarker has conclusively shown the ability to predict treatment response.The field is actively studying various biomarkers,including circulating tumor DNA(ctDNA)in blood,though it’s not commonly studied in NMIBC.The ongoing research in this area is promising,and we anticipate future developments.
 
Marie-Pier St-Laurent教授
不列颠哥伦比亚大学

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