Development and Multicenter Case-Control Validation of Urinary Comprehensive Genomic Profiling for Urothelial Carcinoma Diagnosis, Surveillance, and Risk-Prediction.

Autor:	Salari K; Department of Urology, Massachusetts General Hospital, Boston, Massachusetts.; Center for Genomic Medicine, Massachusetts General Hospital, Boston, Massachusetts.; Broad Institute of MIT and Harvard, Cambridge, Massachusetts., Sundi D; Department of Urology, The Ohio State University Comprehensive Cancer Center & Pelotonia Institute for Immuno-Oncology, Columbus, Ohio., Lee JJ; Department of Urology, Massachusetts General Hospital, Boston, Massachusetts., Wu S; Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts., Wu CL; Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts., DiFiore G; Department of Urology, The Ohio State University Comprehensive Cancer Center & Pelotonia Institute for Immuno-Oncology, Columbus, Ohio., Yan QR; Golden Gate Urology, Oakland, Berkeley and San Francisco, California., Pienkny A; Golden Gate Urology, Oakland, Berkeley and San Francisco, California., Lee CK; Golden Gate Urology, Oakland, Berkeley and San Francisco, California., Oberlin D; Golden Gate Urology, Oakland, Berkeley and San Francisco, California., Barme G; Golden Gate Urology, Oakland, Berkeley and San Francisco, California., Piser J; Golden Gate Urology, Oakland, Berkeley and San Francisco, California., Kahn R; Golden Gate Urology, Oakland, Berkeley and San Francisco, California., Collins E; Golden Gate Urology, Oakland, Berkeley and San Francisco, California., Phillips KG; Convergent Genomics, South San Francisco, California., Caruso VM; Convergent Genomics, South San Francisco, California., Goudarzi M; Convergent Genomics, South San Francisco, California., Garcia-Ransom M; Convergent Genomics, South San Francisco, California., Lentz PS; Convergent Genomics, South San Francisco, California., Evans-Holm ME; Convergent Genomics, South San Francisco, California., MacBride AR; Convergent Genomics, South San Francisco, California., Fischer DS; Convergent Genomics, South San Francisco, California., Haddadzadeh IJ; Convergent Genomics, South San Francisco, California., Mazzarella BC; Convergent Genomics, South San Francisco, California., Gray JW; Oregon Health & Science University, Portland, Oregon., Koppie TM; Oregon Health & Science University, Portland, Oregon.; Willamette Urology, Salem, Oregon., Bicocca VT; Convergent Genomics, South San Francisco, California., Levin TG; Convergent Genomics, South San Francisco, California., Lotan Y; Department of Urology, University of Texas Southwestern Medical Center Dallas, Dallas, Texas., Feldman AS; Department of Urology, Massachusetts General Hospital, Boston, Massachusetts.
Jazyk:	angličtina
Zdroj:	Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2023 Sep 15; Vol. 29 (18), pp. 3668-3680.
DOI:	10.1158/1078-0432.CCR-23-0570
Abstrakt:	Purpose: Urinary comprehensive genomic profiling (uCGP) uses next-generation sequencing to identify mutations associated with urothelial carcinoma and has the potential to improve patient outcomes by noninvasively diagnosing disease, predicting grade and stage, and estimating recurrence risk. Experimental Design: This is a multicenter case-control study using banked urine specimens collected from patients undergoing initial diagnosis/hematuria workup or urothelial carcinoma surveillance. A total of 581 samples were analyzed by uCGP: 333 for disease classification and grading algorithm development, and 248 for blinded validation. uCGP testing was done using the UroAmp platform, which identifies five classes of mutation: single-nucleotide variants, copy-number variants, small insertion-deletions, copy-neutral loss of heterozygosity, and aneuploidy. UroAmp algorithms predicting urothelial carcinoma tumor presence, grade, and recurrence risk were compared with cytology, cystoscopy, and pathology. Results: uCGP algorithms had a validation sensitivity/specificity of 95%/90% for initial cancer diagnosis in patients with hematuria and demonstrated a negative predictive value (NPV) of 99%. A positive diagnostic likelihood ratio (DLR) of 9.2 and a negative DLR of 0.05 demonstrate the ability to risk-stratify patients presenting with hematuria. In surveillance patients, binary urothelial carcinoma classification demonstrated an NPV of 91%. uCGP recurrence-risk prediction significantly prognosticated future recurrence (hazard ratio, 6.2), whereas clinical risk factors did not. uCGP demonstrated positive predictive value (PPV) comparable with cytology (45% vs. 42%) with much higher sensitivity (79% vs. 25%). Finally, molecular grade predictions had a PPV of 88% and a specificity of 95%. Conclusions: uCGP enables noninvasive, accurate urothelial carcinoma diagnosis and risk stratification in both hematuria and urothelial carcinoma surveillance patients. (©2023 The Authors; Published by the American Association for Cancer Research.)
Databáze:	MEDLINE
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