医学
内科学
膀胱切除术
膀胱癌
队列
肿瘤科
化疗
癌症
转移性尿路上皮癌
前瞻性队列研究
癌
阶段(地层学)
胃肠病学
泌尿科
尿路上皮癌
生物
古生物学
作者
Sia V. Lindskrog,Karin Birkenkamp‐Demtröder,Iver Nordentoft,George Laliotis,Philippe Lamy,Emil Christensen,Derrick Renner,Tine G. Andreasen,Naja Lange,Shruti Sharma,Adam C. ElNaggar,Minetta C. Liu,Himanshu Sethi,Alexey Aleshin,Mads Agerbæk,Jørgen Bjerggaard Jensen,Lars Dyrskjøt
标识
DOI:10.1158/1078-0432.ccr-23-1860
摘要
To investigate whether circulating tumor DNA (ctDNA) assessment in patients with muscle-invasive bladder cancer predicts treatment response and provides early detection of metastatic disease.We present full follow-up results (median follow-up: 68 months) from a previously described cohort of 68 neoadjuvant chemotherapy (NAC)-treated patients who underwent longitudinal ctDNA testing (712 plasma samples). In addition, we performed ctDNA evaluation of 153 plasma samples collected before and after radical cystectomy (RC) in a separate cohort of 102 NAC-naïve patients (median follow-up: 72 months). Total RNA sequencing of tumors was performed to investigate biological characteristics of ctDNA shedding tumors.Assessment of ctDNA after RC identified metastatic relapse with a sensitivity of 94% and specificity of 98% using the expanded follow-up data for the NAC-treated patients. ctDNA dynamics during NAC was independently associated with patient outcomes when adjusted for pathologic downstaging (HR = 4.7; P = 0.029). For the NAC-naïve patients, ctDNA was a prognostic predictor before (HR = 3.4; P = 0.0005) and after RC (HR = 17.8; P = 0.0002). No statistically significant difference in recurrence-free survival for patients without detectable ctDNA at diagnosis was observed between the cohorts. Baseline ctDNA positivity was associated with the Basal/Squamous (Ba/Sq) subtype and enrichment of epithelial-to-mesenchymal transition and cell cycle-associated gene sets.ctDNA is prognostic in NAC-treated and NAC-naïve patients with more than 5 years follow-up and outperforms pathologic downstaging in predicting treatment efficacy. Patients without detectable ctDNA at diagnosis may benefit significantly less from NAC, but additional studies are needed.
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