Data from Development and multicenter case-control validation of urinary comprehensive genomic profiling for urothelial carcinoma diagnosis, surveillance, and risk prediction

• DOI: 10.1158/1078-0432.c.6779668.v3
• Publication Date: 2024-09-16T12:37:52Z
• Authors: Keyan Salari; Debasish Sundi; Jason J. Lee; Shulin Wu; Chin-Lee Wu; Gabrielle DiFiore; Q. Robert Yan; Andrew Pienkny; Chi K. Lee; Daniel Oberlin; Greg Barme; Joel Piser; Robert Kahn; Edward Collins; Kevin G. Phillips; Vincent M. Caruso; Mahdi Goudarzi; Monica Garcia-Ransom; Peter S. Lentz; Martha E. Evans-Holm; Andrew R. MacBride; Daniel S. Fischer; Iden J. Haddadzadeh; Brian C. Mazzarella; Joe W. Gray; Theresa M. Koppie; Vincent T. Bicocca; Trevor G. Levin; Yair Lotan; Adam S. Feldman
• Keywords: Profiling (computer programming)

<div>Abstract<p>Purpose: Urinary comprehensive genomic profiling (uCGP) uses next-generation sequencing to identify mutations associated with urothelial carcinoma (UC) and has the potential improve patient outcomes by noninvasively diagnosing disease, predicting grade stage, estimating recurrence risk. Experimental Design: This is a multicenter case-control study utilizing banked urine specimens collected from patients undergoing initial diagnosis/hematuria workup or UC surveillance. A total of 581 samples were analyzed uCGP: 333 for disease classification grading algorithm development, 248 blinded validation. uCGP testing was done using UroAmp<sup>TM</sup> platform, which identifies five classes mutation: single-nucleotide variants, copy-number small insertion-deletions, copy-neutral loss heterozygosity, aneuploidy. UroAmp algorithms tumor presence, grade, risk compared cytology, cystoscopy, pathology. Results: had validation sensitivity/specificity 96%/90% cancer diagnosis in hematuria demonstrated negative predictive value (NPV) 99%. positive diagnostic likelihood ratio (DLR) 9.2 DLR 0.05 demonstrate ability risk-stratify presenting hematuria. In surveillance patients, binary an NPV 91%. prediction significantly prognosticated future (hazard 6.2), whereas clinical factors did not. (PPV) comparable cytology (45% vs 42%) much higher sensitivity (79% 25%). Finally, molecular predictions PPV 88% specificity 95%. Conclusions: enables noninvasive, accurate stratification both patients.</p></div>