TY - JOUR
T1 - Performance of novel non-invasive urine assay UroSEEK in cohorts of equivocal urine cytology
AU - Rodriguez Pena, Maria Del Carmen
AU - Springer, Simeon U.
AU - Taheri, Diana
AU - Li, Lu
AU - Tregnago, Aline C.
AU - Eich, Marie Lisa
AU - Eltoum, Isam Eldin A.
AU - VandenBussche, Christopher J.
AU - Papadopoulos, Nickolas
AU - Kinzler, Kenneth W.
AU - Vogelstein, Bert
AU - Netto, Georges J
N1 - Funding Information:
Support provided by Henry and Marsha Laufer, Virginia and D.K. Ludwig Fund for Cancer Research, the Commonwealth Foundation, John Templeton Foundation, Conrad R. Hilton Foundation and grants from the NIH (T32 GM007309/GM/NIGMS NIH HHS/United States; P30 CA077598/CA/NCI NIH HHS/United States; P30 CA006973/CA/NCI NIH HHS/United States; R01 ES019564/ES/NIEHS NIH HHS/United States). All sequencing was performed at the Sol Goldman Sequencing Facility at Johns Hopkins.
Publisher Copyright:
© 2019, Springer-Verlag GmbH Germany, part of Springer Nature.
PY - 2020/3/1
Y1 - 2020/3/1
N2 - Urine cytology is an essential element of the diagnostic work up of hematuria. A significant proportion of cases continue to be placed in the “atypical” or “suspicious” categories of the Paris system for urine cytology, posing difficulty in patient management. We report on the performance of our recently described urine-based assay “UroSEEK” in cases with equivocal diagnosis in patients who are investigated for bladder cancer. Urine samples were collected from two cohorts. The first consisted of patients who presented with hematuria or lower urinary tract symptoms (early detection cohort) and the second of patients that are in follow-up for prior bladder cancer (surveillance cohort). Urine samples were analyzed for mutations in 11 genes and aneuploidy. In the early detection setting, we found high sensitivity and specificity (96% and 88%, respectively) and a strong negative predictive value of 99%. The assay performance was less robust in the surveillance cohort (sensitivity of 74%, specificity of 72%, and negative predictive value of 53%). UroSEEK demonstrated a notable lead time to cancer diagnosis. Seven cases in the early detection cohort and 71 surveillance cases were detected at least 6 months prior to clinical diagnosis. Our results suggest a potential role for UroSEEK assay in guiding management of patients with atypical urine cytology if confirmed in future prospective trials.
AB - Urine cytology is an essential element of the diagnostic work up of hematuria. A significant proportion of cases continue to be placed in the “atypical” or “suspicious” categories of the Paris system for urine cytology, posing difficulty in patient management. We report on the performance of our recently described urine-based assay “UroSEEK” in cases with equivocal diagnosis in patients who are investigated for bladder cancer. Urine samples were collected from two cohorts. The first consisted of patients who presented with hematuria or lower urinary tract symptoms (early detection cohort) and the second of patients that are in follow-up for prior bladder cancer (surveillance cohort). Urine samples were analyzed for mutations in 11 genes and aneuploidy. In the early detection setting, we found high sensitivity and specificity (96% and 88%, respectively) and a strong negative predictive value of 99%. The assay performance was less robust in the surveillance cohort (sensitivity of 74%, specificity of 72%, and negative predictive value of 53%). UroSEEK demonstrated a notable lead time to cancer diagnosis. Seven cases in the early detection cohort and 71 surveillance cases were detected at least 6 months prior to clinical diagnosis. Our results suggest a potential role for UroSEEK assay in guiding management of patients with atypical urine cytology if confirmed in future prospective trials.
KW - Aneuploidy analysis
KW - Atypical urine cytology
KW - DNA mutational analysis
KW - Non-invasive urine assay
KW - Urinary bladder neoplasms
KW - UroSEEK
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U2 - 10.1007/s00428-019-02654-1
DO - 10.1007/s00428-019-02654-1
M3 - Article
C2 - 31482302
AN - SCOPUS:85072100160
VL - 476
SP - 423
EP - 429
JO - Virchows Archiv - Abteilung A Pathologische Anatomie
JF - Virchows Archiv - Abteilung A Pathologische Anatomie
SN - 0945-6317
IS - 3
ER -