无法检测到的自由基前膀胱切除术循环肿瘤DNA状态预测肿瘤学结果改善
Undetectable pre-radical cystectomy circulating tumour DNA status predicts improved oncological outcomes
影响因子:4.40000
分区:医学2区 / 泌尿学与肾脏学2区
发表日期:2025 Mar
作者:
Reuben Ben-David, Sarah Lidagoster, Jack Geduldig, Kaushik P Kolanukuduru, Yuval Elkun, Neeraja Tillu, Asher Mandel, Mohammed Almoflihi, Basil Kaufmann, Kyrollis Attalla, Reza Mehrazin, Peter Wiklund, John P Sfakianos
摘要
在自由基宫颈切除术（RC）之前评估未检测到的肿瘤循环肿瘤DNA（CTDNA）的患者的无复发生存期（RFS），并评估那些从可检测到的CTDNA状态转化为RF后持续不可检测的ctDNA状态的人，是否从可检测到的CTDNA状态转化为持续的CTDNA状态，并且持续了持续的CTDNA状态。在2021 - 2023年期间收集的肿瘤信息的CTDNA分析。 CTDNA状态已从PRE-RC样品中获悉。最小残留疾病（MRD）窗口定义为RC后90天。使用Kaplan-Meier方法评估RFS。进行了COX回归分析以查找疾病复发的预测指标。该队列包括135例647个CTDNA分析的患者。中位数（四分位数[IQR]）年龄为71（63-77）年。在11（7-18）个月的中位数（IQR）随访中，有41例（30％）复发。 54例患者（40％）发现了RC前RC无法检测的CTDNA状态。 6、12和21个月的RFS率分别为98％，93％和82％。在可用于转换动力学分析的MRD窗口处的77例无法检测到的CTDNA状态的患者中，有43例持续无法检测到的CTDNA状态（在PRE-RC和MRD窗口处），从可检测到的MRD前RC转换为MRD不可检测的状态（转换组）。持续的不可检测的组的RF明显优于转换组（日志量，p <0.001），12个月的RFS率为97％，为51％，而188％的RFS率分别为88％和51％。在COX多元分析中，仅转化组状态预测疾病复发。患有不可检测的RC CTDNA状态的患者具有有利的预后，并且可能是治疗降低的候选者。与转换组相比，那些持续无法检测到的ctDNA的RF具有优越的RF。 RC前CTDNA状态应纳入检查CTDNA在临床决策中使用的试验。
Abstract
To assess recurrence-free survival (RFS) in patients with undetectable tumour-informed circulating tumour DNA (ctDNA) before radical cystectomy (RC) and evaluate if those who converted from detectable to undetectable ctDNA status after RC have similar RFS outcomes as those with persistently undetectable ctDNA status.Patients who underwent RC had prospectively and longitudinally collected tumour-informed ctDNA analyses during 2021-2023. ctDNA status was informed from the pre-RC specimen. The minimal residual disease (MRD) window was defined as the initial 90 days after RC. RFS was evaluated using the Kaplan-Meier method. Cox regression analysis was performed to find predictors of disease recurrence.The cohort included 135 patients with 647 ctDNA analyses. The median (interquartile range [IQR]) age was 71 (63-77) years. Over a median (IQR) follow-up of 11 (7-18) months, 41 patients (30%) had a recurrence. Pre-RC undetectable ctDNA status was found in 54 patients (40%). The RFS rates at 6, 12, and 21 months were 98%, 93%, and 82%, respectively. Of 77 patients with undetectable ctDNA status at the MRD window available for conversion dynamics analysis, 43 had persistently undetectable ctDNA status (both at pre-RC and MRD window) and 31 converted from pre-RC detectable to MRD undetectable status (conversion group). The persistently undetectable group had significantly better RFS than the conversion group (log-rank, P < 0.001), with 12-month RFS rates of 97% vs 51%, and 18-month RFS rates of 88% vs 51%, respectively. On Cox multivariate analysis, only the conversion group status predicted disease recurrence.Patients with undetectable pre-RC ctDNA status have a favourable prognosis and may be candidates for treatment de-escalation. Those with persistently undetectable ctDNA had superior RFS compared to the conversion group. Pre-RC ctDNA status should be incorporated into trials examining ctDNA use in clinical decision-making.