Fox Chase Cancer Center, Philadelphia, PA.
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.
JCO Precis Oncol. 2024 Jun;8:e2300362. doi: 10.1200/PO.23.00362.
There is significant interest in identifying complete responders to neoadjuvant chemotherapy (NAC) before radical cystectomy (RC) to potentially avoid removal of a pathologically benign bladder. However, clinical restaging after NAC is highly inaccurate. The objective of this study was to develop a next-generation sequencing-based molecular assay using urine to enhance clinical staging of patients with bladder cancer.
Urine samples from 20 and 44 patients with bladder cancer undergoing RC were prospectively collected for retrospective analysis for molecular correlate analysis from two clinical trials, respectively. The first cohort was used to benchmark the assay, and the second was used to determine the performance characteristics of the test as it correlates to responder status as measured by pathologic examination.
First, to benchmark the assay, known mutations identified in the tissue (M) of patients from the Accelerated Methotrexate, Vinblastine, Doxorubicin, Cisplatin trial (ClinicalTrials.gov identifier: NCT01611662, n = 16) and a cohort from University of California-San Francisco (n = 4) were cross referenced against mutation profiles from urine (M). We then determined the correlation between M persistence and residual disease in pre-RC urine samples from a second prospective clinical trial (The pT0 trial; ClinicalTrials.gov identifier: NCT02968732). Residual M status correlated strongly with residual disease status (pT0 trial; n = 44; = .0092) when M from urine supernatant and urine pellet were assessed separately and analyzed in tandem. The sensitivity, specificity, PPV, and NPV were 91%, 50%, 86%, and 63% respectively, with an overall accuracy of 82% for this second cohort.
M are representative of M and thus can be used to enhance clinical staging of urothelial carcinoma. Urine biopsy may be used as a reliable tool that can be further developed to identify complete response to NAC in anticipation of safe RC avoidance.
在根治性膀胱切除术 (RC) 之前，人们对识别新辅助化疗 (NAC) 的完全缓解者有很大的兴趣，以避免切除病理良性的膀胱。然而，NAC 后的临床分期高度不准确。本研究的目的是开发一种基于下一代测序的分子检测方法，利用尿液来增强膀胱癌患者的临床分期。
前瞻性收集了 20 例和 44 例接受 RC 的膀胱癌患者的尿液样本，分别用于两项临床试验的回顾性分析，以进行分子相关性分析。第一组用于基准测试，第二组用于确定该测试的性能特征，因为它与病理检查测量的反应者状态相关。
首先，为了基准测试，来自加速甲氨蝶呤、长春花碱、多柔比星、顺铂试验（ClinicalTrials.gov 标识符：NCT01611662，n = 16）和加利福尼亚大学旧金山分校（n = 4）的患者组织（M）中确定的已知突变与尿液（M）的突变谱进行交叉引用。然后，我们确定了第二个前瞻性临床试验（pT0 试验；ClinicalTrials.gov 标识符：NCT02968732）中 RC 前尿液样本中 M 持续性与残留疾病之间的相关性。当单独评估和串联分析尿液上清液和尿液沉淀中的 M 时，残留 M 状态与残留疾病状态强烈相关（pT0 试验；n = 44； =.0092）。对于第二个队列，灵敏度、特异性、PPV 和 NPV 分别为 91%、50%、86%和 63%，总体准确率为 82%。
M 是 M 的代表，因此可以用于增强尿路上皮癌的临床分期。尿液活检可以作为一种可靠的工具，进一步开发用于识别 NAC 的完全反应，以避免安全的 RC。
