Of the patients undergoing radical cystectomy, 20–80% experience relapse. Minimally invasive methods for early detection of metastatic relapse after cystectomy and for monitoring ongoing therapy are urgently needed to improve individualised follow-up and treatment. Therefore, we evaluated the use of circulating tumour DNA (ctDNA) in plasma and urine to detect metastatic relapse after cystectomy and measure treatment efficacy. We exome sequenced tumour and germline DNA from patients with muscle-invasive bladder cancer and monitored ctDNA in 370 liquid biopsies throughout the disease courses by 84 personalised digital droplet polymerase chain reaction assays targeting 61 genes. Patients were prospectively recruited between 2013 and 2017. Patients with metastatic relapse had significantly higher ctDNA levels compared with disease-free patients (p < 0.001). The median positive lead time between ctDNA detection in plasma and diagnosis of relapse was 101 d after cystectomy (range 0–932 d). Early detection of metastatic relapse and treatment response using liquid biopsies represents a novel, highly sensitive tool for monitoring patients, supporting clinicians, and guiding treatment decisions.

Patient summary

Measurement of tumour-specific mutations in plasma and urine may be a powerful tool to monitor response during treatment and identify early signs of metastatic disease.

中文翻译：

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液体活检分析监测晚期膀胱癌的治疗反应和转移复发

在接受根治性膀胱切除术的患者中，有20–80％的患者复发。迫切需要一种微创方法，用于早期发现膀胱切除术后的转移性复发并监测正在进行的治疗，以改善个体化的随访和治疗。因此，我们评估了血浆和尿液中循环肿瘤DNA（ctDNA）的使用，以检测膀胱切除术后的转移性复发并评估治疗效果。我们对患有肌肉浸润性膀胱癌的患者的肿瘤和种系DNA进行了外显子测序，并通过针对61个基因的84种个性化数字液滴聚合酶链反应测定法在整个疾病过程中对370例液体活检组织中的ctDNA进行了监测。预期在2013年至2017年之间招募患者。与无病患者相比，转移性复发患者的ctDNA水平明显更高（p  <0.001）。膀胱切除术后血浆ctDNA检测与复发诊断之间的中位阳性前置时间为101 d（范围为0–932 d）。使用液体活组织检查早期发现转移性复发和治疗反应代表了一种新型的，高度敏感的工具，可用于监测患者，支持临床医生并指导治疗决策。

病人总结

血浆和尿液中肿瘤特异性突变的测量可能是监测治疗过程中反应并确定转移性疾病早期迹象的有力工具。