medRxiv : the preprint server for health sciences · 2026
Evaluation of Urinary Circulating Tumor DNA to Detect Minimal Residual Disease in Patients with High-Risk Non-Muscle Invasive Bladder Cancer.
СтатьяПрепринтНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Li Roger, Linscott Joshua, Murthy Prithvi, Rose Kyle, Pak Young, Zhang Frank, Huang Yong, Grass G Daniel, Chatzkel Jonathan, Hahn Noah M, McConkey David J, Meeks Joshua J, Daneshmand Siamak, Flaig Thomas W, Lerner Seth P, Zemp Logan, Poch Michael A, Spiess Philippe E, Sexton Wade J, Gilbert Scott M, Xu Hongzhi, Du Pan, Jia Shidong, Wang Xuefeng
Аннотация
PURPOSE: Restaging transurethral resection of bladder tumor (reTURBT) is the standard-of-care for some patients with high-risk non-muscle invasive bladder cancer (NMIBC). However, it may lead to complications and biomarkers to avoid unnecessary reTURBT are needed.
MATERIALS AND METHODS: Patients with high-risk NMIBC undergoing reTURBT were prospectively enrolled. Whole-exome sequencing along with low-pass whole-genome sequencing were performed on index TURBT samples to generate mutational profiles and copy number variation. Up to 50 personalized mutations and a fixed panel of 500 hotspot mutations were used for detecting variants from urine samples collected prior to reTURBT. Using a prespecified algorithm, tumor fraction (TF) and copy number burden (CNB) score were used to measure minimal residual disease and correlated with reTURBT pathology.
RESULTS: Overall, 72/76 urine samples collected from patients with high-risk NMIBC prior to reTURBT passed quality check. From the indext TURBT specimens, a median of 39 personalized variants from the index TURBT were used for disease tracking. Overall, median TF was 0.206 vs. 0.001 in patients with and without residual tumor, respectively (p<0.001). Similarly, CNB score was elevated (7.34 vs. 4.02, p<0.001). utDNA achieved sensitivity of 97.8% and specificity of 69.2%, with area under the curve (AUC) of 0.932 in predicting disease found on reTURBT. Analyses of the index and reTURBT tissue and urine mutational profiles provided evidence for underdiagnosis of subclinical disease at the time of reTURBT.
CONCLUSION: Paired personalized and panel utDNA can be used to accurately detect residual disease in patients with high-risk NMIBC with potentially wide-ranging clinical applications.
MATERIALS AND METHODS: Patients with high-risk NMIBC undergoing reTURBT were prospectively enrolled. Whole-exome sequencing along with low-pass whole-genome sequencing were performed on index TURBT samples to generate mutational profiles and copy number variation. Up to 50 personalized mutations and a fixed panel of 500 hotspot mutations were used for detecting variants from urine samples collected prior to reTURBT. Using a prespecified algorithm, tumor fraction (TF) and copy number burden (CNB) score were used to measure minimal residual disease and correlated with reTURBT pathology.
RESULTS: Overall, 72/76 urine samples collected from patients with high-risk NMIBC prior to reTURBT passed quality check. From the indext TURBT specimens, a median of 39 personalized variants from the index TURBT were used for disease tracking. Overall, median TF was 0.206 vs. 0.001 in patients with and without residual tumor, respectively (p<0.001). Similarly, CNB score was elevated (7.34 vs. 4.02, p<0.001). utDNA achieved sensitivity of 97.8% and specificity of 69.2%, with area under the curve (AUC) of 0.932 in predicting disease found on reTURBT. Analyses of the index and reTURBT tissue and urine mutational profiles provided evidence for underdiagnosis of subclinical disease at the time of reTURBT.
CONCLUSION: Paired personalized and panel utDNA can be used to accurately detect residual disease in patients with high-risk NMIBC with potentially wide-ranging clinical applications.