Development and Multicenter Case-Control Validation of Urinary Comprehensive Genomic Profiling for Urothelial Carcinoma Diagnosis, Surveillance, and Risk-Prediction.
Clin Cancer Res
; 29(18): 3668-3680, 2023 09 15.
Article
em En
| MEDLINE
| ID: mdl-37439796
ABSTRACT
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. EXPERIMENTALDESIGN:
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.
Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
1_ASSA2030
/
2_ODS3
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Bexiga Urinária
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Carcinoma de Células de Transição
Tipo de estudo:
Clinical_trials
/
Diagnostic_studies
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Etiology_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
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Screening_studies
Limite:
Humans
Idioma:
En
Revista:
Clin Cancer Res
Ano de publicação:
2023
Tipo de documento:
Article