Transl Res. 2019 Feb 7. pii: S1931-5244(19)30025-8. doi: 10.1016/j.trsl.2019.02.003. [Epub ahead of print]
Ability of a urine gene expression classifier to reduce the number of follow-up cystoscopies in bladder cancer patients.
Montalbo R1, Lozano JJ2, Izquierdo L1, Ingelmo-Torres M1, BaÑos C1, Palou J3, Van der Heijden AG4, Medina R5, Schmidbauer J6, Prat A7, Ribal MJ1, Alcaraz A1, Mengual L8.
This study aimed to improve our previous urine gene expression classifiers focusing on the detection of non-high-risk non-muscle-invasive bladder cancer (NMIBC), and develop a new classifier able to decrease the frequency of cystoscopies during bladder cancer (BC) patients' surveillance. A total of 597 urines from BC patients, controls and patients in follow-up for BC (PFBC) were included. The study has 3 phases. In the urinary biomarker discovery phase, 84 urines from BC and control patients were retrospectively included and analyzed by RNA sequencing. In the classifier development phase, a total of 132 selected genes from previous phase were evaluated by nCounter in 214 prospectively collected urines from PFBC (98 with tumor). A diagnostic classifier was generated by logistic regression. Finally, in the classifier validation phase, a multicentric and international cohort of 248 urines (134 BC and 114 nonrecurrent PFBC) was used to validate classifier performance. A total of 521 genes were found differentially expressed between non-high-risk NMIBC samples and all other groups (P < 0.05). An 8-gene diagnostic classifier with an area under curve (AUC) of 0.893 was developed. Validation of this classifier in a cohort of PFBC achieved an overall sensitivity (SN) and a negative predictive value (NPV) of 96% and 97%, respectively (AUC = 0.823). Notably, this accuracy was maintained in non-high-risk NMIBC group (SN = 94%; NPV = 98%). In conclusion, this 8-gene expression classifier has high SN and NPV in a real clinical scenario. The use of this classifier can reduce the number of follow-up cystoscopies in PFBC, although assessing its final place in clinical setting is necessary.
Copyright © 2019 Elsevier Inc. All rights reserved.