无法检测到的根治性膀胱切除术前循环肿瘤 DNA 状态预示着肿瘤结果的改善。
Undetectable pre-radical cystectomy circulating tumour DNA status predicts improved oncological outcomes.
发表日期:2024 Oct 16
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
来源:
BJU INTERNATIONAL
摘要:
评估根治性膀胱切除术 (RC) 前肿瘤相关循环肿瘤 DNA (ctDNA) 无法检测到的患者的无复发生存 (RFS),并评估 RC 后从可检测到 ctDNA 状态转为不可检测的患者是否与持续存在肿瘤相关的患者具有相似的 RFS 结果。无法检测到的 ctDNA 状态。接受 RC 的患者在 2021 年至 2023 年期间前瞻性地纵向收集了肿瘤相关的 ctDNA 分析。 ctDNA 状态是从预 RC 样本中得知的。微小残留病 (MRD) 窗口定义为 RC 后最初 90 天。 RFS 使用 Kaplan-Meier 方法进行评估。进行 Cox 回归分析以寻找疾病复发的预测因素。该队列包括 135 名患者,进行了 647 项 ctDNA 分析。中位年龄(四分位距 [IQR])为 71(63-77)岁。在 11(7-18) 个月的中位 (IQR) 随访中,41 名患者 (30%) 出现复发。在 54 名患者 (40%) 中发现 RC 前检测不到的 ctDNA 状态。 6、12 和 21 个月时的 RFS 率分别为 98%、93% 和 82%。在可用于转换动态分析的 MRD 窗口中 ctDNA 状态为不可检测的 77 名患者中,43 名 ctDNA 状态持续不可检测(在 RC 前和 MRD 窗口均如此),31 名患者从 RC 前可检测到 MRD 不可检测状态(转换组)。持续不可检测组的 RFS 显着优于转换组(对数秩,P<0.001),12 个月 RFS 率分别为 97% 和 51%,18 个月 RFS 率分别为 88% 和 51%。在 Cox 多变量分析中,只有转换组状态才能预测疾病复发。RC 前 ctDNA 状态无法检测到的患者预后良好,可能是治疗降级的候选者。与转化组相比,那些 ctDNA 持续检测不到的人具有更好的 RFS。 RC 前 ctDNA 状态应纳入检查 ctDNA 在临床决策中使用的试验中。© 2024 BJU International。
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.© 2024 BJU International.