A prospective validation of nomograms based on BC-116 and BC-106 urine peptide biomarker panels for bladder cancer diagnostics and monitoring

Purpose: Non-invasive urine-based biomarkers for bladder cancer (BC) diagnosis and surveillance can potentially improve current diagnostic and monitoring protocols by guiding cystoscopy. Here, we aim to access the diagnostic performance of nomograms based on published biomarker panels for BC detection (BC-116) and monitoring of recurrence (BC-106) in combination with cytology, in two prospectively collected patient cohorts. Experimental Design: 602 recruited patients were screened for presence of BC, out of which 551 were found eligible for further analysis. For the primary setting, urine samples from 73 eligible patients were analyzed from those diagnosed with primary BC (n=27) and benign urological disorders (n=46). For the surveillance setting, 478 eligible patients were considered (83 BC recurrences; 395 negative for recurrence). Urine samples were analyzed with capillary electrophoresis coupled to mass spectrometry and the biomarker score was estimated via a support vector machine-based software. Results: Validation of the BC-116 biomarker panel resulted in 89% sensitivity and 67% specificity (AUCBC-116=0.82), similar to the published estimates. The nomogram based on cytology and BC-116 resulted in good (AUCNom116=0.85) but not significantly better performance than the BC-116 alone (P=0.5672). BC-106 biomarker panel showed 89% sensitivity and 32% specificity for surveillance, while improved performance was achieved when a nomogram including BC-106 and cytology was evaluated (AUCNom106=0.82), significantly outperforming both cytology (AUCcyt=0.72;P=0.0022) and BC-106 alone (AUCBC-106=0.67;P=0.0012). Conclusions: BC-116 biomarker panel is a useful test for detecting primary BC. BC-106 classifier integrated with cytology and showing >95% negative predictive value, might be useful for decreasing the number of cystoscopies during surveillance.