Narayan Vikram M, Tholomier Come, Mokkapati Sharada, Martini Alberto, Caruso Vincent M, Goudarzi Mahdi, Mazzarella Brian C, Phillips Kevin G, Bicocca Vincent T, Levin Trevor G, Yla-Herttuala Seppo, McConkey David J, Dinney Colin P N
Department of Urology, University of Texas MD Anderson Cancer Center, Houston, TX, USA; Department of Urology, Emory University, Atlanta, GA, USA.
Department of Urology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Eur Urol Oncol. 2025 Apr;8(2):425-434. doi: 10.1016/j.euo.2024.09.016. Epub 2024 Oct 15.
Urinary tumor DNA (utDNA) profiling identifies mutations associated with urothelial carcinoma and can be used to detect minimal residual disease (MRD). We evaluate the utility of utDNA profiling to predict treatment failure in bacillus Calmette-Guérin-unresponsive high-grade (HG) non-muscle-invasive bladder cancer (NMIBC) treated with nadofaragene firadenovec.
Urine was collected from participants prior to induction (n = 32) and at their 3-mo evaluation (n = 18) in the parallel-arm, phase 2 study (NCT01687244) of nadofaragene firadenovec. The UroAmp MRD assay (Convergent Genomics, South San Francisco, CA, USA) was used to perform utDNA testing. Risk of HG NMIBC recurrence was determined using two algorithm versions, and recurrence-free survival (RFS) was assessed using a Kaplan-Meier analysis.
TP53, TERT, PIK3CA, ARID1A, PLEKHS1, ELF3, and ERBB2 were the most prevalently mutated genes. With pretreatment urine, the validated MRD algorithm resulted in 12-mo RFS of 56% for negative and 22% for positive patients (p = 0.097). The experimental, enhanced algorithm classified two additional patients as positive, giving RFS of 71% for negative and 20% for positive patients (p = 0.012). With 3-mo urine, both algorithms gave RFS of 100% for negative and 38% for positive patients (p = 0.038). Longitudinal utDNA testing classified patients as negative (7%), complete responders (13%), partial responders (27%), unresponsive (20%), and expanding (33%).
Urinary MRD testing after nadofaragene firadenovec induction provided statistically significant prognostication of recurrence among phase 2 trial participants.
By analyzing urine-borne tumor DNA, we can help determine which patients with high-grade non-muscle-invasive bladder cancer are at the greatest risk of recurrence when receiving second-line therapy.
尿肿瘤DNA（utDNA）分析可识别与尿路上皮癌相关的突变，并可用于检测微小残留病（MRD）。我们评估utDNA分析在预测接受纳多柔比星腺病毒载体治疗的卡介苗无反应的高级别（HG）非肌层浸润性膀胱癌（NMIBC）治疗失败中的效用。
在纳多柔比星腺病毒载体的平行组2期研究（NCT01687244）中，在诱导治疗前（n = 32）和3个月评估时（n = 18）从参与者收集尿液。使用UroAmp MRD检测法（美国加利福尼亚州南旧金山的Convergent Genomics公司）进行utDNA检测。使用两个算法版本确定HG NMIBC复发风险，并使用Kaplan-Meier分析评估无复发生存期（RFS）。
TP53、TERT、PIK3CA、ARID1A、PLEKHS1、ELF3和ERBB2是最常发生突变的基因。对于治疗前尿液，经过验证的MRD算法得出阴性患者12个月RFS为56%，阳性患者为22%（p = 0.097）。实验性的增强算法将另外两名患者分类为阳性，阴性患者RFS为71%，阳性患者为20%（p = 0.012）。对于3个月时的尿液，两种算法得出阴性患者RFS均为100%，阳性患者为38%（p = 0.038）。纵向utDNA检测将患者分类为阴性（7%）、完全缓解者（13%）、部分缓解者（27%）、无反应者（20%）和病情进展者（33%）。
纳多柔比星腺病毒载体诱导治疗后的尿液MRD检测为2期试验参与者的复发提供了具有统计学意义的预后评估。
通过分析尿液中的肿瘤DNA，我们可以帮助确定哪些高级别非肌层浸润性膀胱癌患者在接受二线治疗时复发风险最高。
