Urinary protein biomarker panel for the detection of recurrent bladder cancer.
BACKGROUND
Up to 70% of patients with non-muscle-invasive bladder cancer (NMIBC) experience disease recurrence, making it one of the most prevalent cancers in the United States. The purpose of this study was to test the performance of a multiplex urinary biomarker assay for the monitoring of voided urine for recurrent bladder cancer.


METHODS
This retrospective, multicenter study included a total of 125 subjects with a history of bladder cancer. Voided urine specimens were collected before procedure from these subjects (53 with confirmed tumor recurrence and 72 with confirmed non-tumor recurrence) for analysis. A prediction rule generated from the performance characteristics of 10 single biomarkers (IL8, MMP9, MMP10, SERPINA1, VEGFA, ANG, CA9, APOE, SERPINE1, and SDC1) was measured using ELISA. The diagnostic performance of the biomarker panel was assessed using receiver operator curves (ROC) and descriptive statistical values (e.g., sensitivity and specificity).


RESULTS
The combination of all 10 biomarkers outperformed any single biomarker with a calculated AUROC for the diagnostic panel of 0.904 [95% confidence interval (CI), 0.853-0.956]. The multiplex assay achieved an overall sensitivity of 79% and specificity of 88% for recurrent bladder cancer and significantly outperformed the Urovysion cytogenetic assay (sensitivity 42%, specificity 94%) and voided urinary cytology (sensitivity 33%, specificity 90%).


CONCLUSIONS
A diagnostic panel of 10 urinary biomarkers that accurately detects primary bladder cancer also performs well for the detection of recurrent bladder cancer.


CONCLUSIONS
The identification of a reliable urine-based surveillance and detection assay would be of benefit to both patients and the healthcare system.
Authors' Affiliations: Cancer Research Institute, MD Anderson Cancer Center, Orlando; Nonagen Bioscience Corp; Clinical & Translational Research Program, University of Hawaii Cancer Center, Honolulu, Hawaii; and crosser@cc.hawaii.edu.
Charles J
CJ
Rosser
Department of Biostatistics, The University of Florida, Gainesville;
Myron
M
Chang
Department of Biostatistics, The University of Florida, Gainesville;
Yunfeng
Y
Dai
Authors' Affiliations: Cancer Research Institute, MD Anderson Cancer Center, Orlando;
Shanti
S
Ross
Laboratory and Department of Urology, Hospital Clínic, Universitat de Barcelona. IDIBAPS Barcelona, Spain.
Lourdes
L
Mengual
Laboratory and Department of Urology, Hospital Clínic, Universitat de Barcelona. IDIBAPS Barcelona, Spain.
Antonio
A
Alcaraz
Authors' Affiliations: Cancer Research Institute, MD Anderson Cancer Center, Orlando; Nonagen Bioscience Corp; Department of Health Sciences Research, Mayo Clinic, Jacksonville, Florida;
Steve
S
Goodison
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000652:urine*; D002295:Carcinoma, Transitional Cell / Q000473:pathology* / Q000652:urine*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000652:urine*; D012372:ROC Curve; D012189:Retrospective Studies; D001749:Urinary Bladder Neoplasms / Q000473:pathology* / Q000652:urine*
D014408:Biomarkers, Tumor