未检测到的前-膀胱切除术循环肿瘤DNA状态预测改善的肿瘤学预后

Undetectable pre-radical cystectomy circulating tumour DNA status predicts improved oncological outcomes

BJU INTERNATIONAL

影响因子:4.4

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

DOI: 10.1111/bju.16556

摘要

为了评估在进行根治性膀胱切除术（RC）前未检测到的肿瘤特异性循环肿瘤DNA（ctDNA）与复发无病生存（RFS）的关系，并探讨在RC后由检测到转为未检测的ctDNA状态的患者是否具有与持续未检测状态相似的预后。2021年至2023年间，接受RC的患者进行了前瞻性、纵向的肿瘤特异性ctDNA检测分析。ctDNA状态基于术前样本判定。最小残留疾病（MRD）窗口定义为RC后初始的90天内。使用Kaplan-Meier法评估RFS，并通过Cox回归分析寻找疾病复发的预测因素。研究共包含135例患者，进行了647次ctDNA分析，年龄中位数（四分位间距）为71（63-77）岁。随访中位数为11（7-18）个月，41例（30%）发生复发。术前未检测到的ctDNA状态见于54例（40%）。6、12和21个月的RFS率分别为98%、93%和82%。在77例在MRD窗口期进行转化动态分析的患者中，43例持续未检测（术前及MRD窗口均未检测），31例由术前检测到的阳性转为MRD期阴性（转化组）。持续未检测组的RFS显著优于转化组（log-rank P<0.001），12个月RFS率分别为97%对比51%，18个月为88%对比51%。Cox多变量分析显示，只有转化组状态预测疾病复发。未检测到的术前ctDNA状态预示良好的预后，可能适合治疗减轻。持续未检测组的RFS优于转化组。术前ctDNA状态应纳入临床试验，辅助临床决策。

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.