Abbreviations BC bladder cancer NMIBC
Abbreviations: BC = Calcipotriol cancer; NMIBC = non-muscle invasive bladder cancer; SN = sensitivity; SP = specificity; LG = low grade; NR-PFBC = non-recurrent patients in follow-up for bladder cancer;
From the Department and Laboratory of Urology, Hospital Clınic, Institut d’Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Centre de Recerca Biomedica CELLEX, Universitat de Barcelona, Barcelona, Spain; Bioinformatics Platform, CIBEREHD, Barcelona, Spain; Department of Urology, Fundacio Puigvert, Barcelona, Spain; Department of Urology, Radboud University Medical Centre, Nijmegen, the Netherlands; Hospital Universitario Virgen del Rocıo/CSIC/Universidad de Sevilla, Sevilla, Spain; Department of Urology, Medical University of Vienna, Vienna, Aus-tria; Oncology Department, Hospital Clınic, Universitat de Barcelona, Barcelona, Spain.
Reprint requests: Lourdes Mengual, Department and Laboratory of Urology, Hospital Clınic, Institut d’Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Centre de Recerca Biomedica CELLEX, Office B22, C/Casanova, 143, 08036 Barcelona, Spain. e-mail: [email protected]
74 Montalbo et al Translational Research
C = control; MIBC = muscle invasive bladder cancer; PCA = principal component analysis; FDR = false discovery rate; FC = fold change; AUC = area under curve; NPV = negative predictive value; PPV = positive predictive value; HG = high grade; RT-qPCR = reverse transcription quantita-tive PCR; GO = gene ontology
AT A GLANCE COMMENTARY
Cystoscopy, combined in some cases with urine cytology, is considered the standard of care for bladder cancer (BC) surveillance, although it has some limitations, especially its invasiveness. Cytology, the non-invasive methodology, has inter-observer variability and low sensitivity in low-grade tumors and, precisely, the majority of recurrent patients under surveillance for BC pres-ent low grade disease.
Here we have developed and validated a urine gene expression classifier with an overall high sensitivity and negative predictive value useful to detect BC during patients’ surveillance. Notably, this high accuracy is maintained in the detection of low grade disease. The use of this classifier in the clinical setting would allow us to replace cys-toscopy during follow-up or lower cystoscopy fre-quency in a routine fashion. Furthermore, the classifier is based on an effortless and uncompli-cated methodology which allows for easy transla-tion into clinical practice.
Seventy to 80 percent of bladder cancer (BC) cases are non muscle-invasive BC (NMIBC) at diagnosis, of which 20 to 80%, depending of the risk group, will have 1 or several recurrences. Consequently, NMIBC patients require frequent and long-term surveillance. The follow-up (FU) schedule consists of cystoscopy and in case of high-risk NMIBC, cystoscopy combined with urine cytology. Depending on the patient’s risk profile, the European Association of Urology guide-lines recommend upto 15 cystoscopies during the first 5 years of FU.1
Cystoscopy is an invasive technique with patient dis-comfort and possible complications. Moreover, it has been estimated that it can overlook 10% 20% of the papillary lesions and 50% of flat bladder lesions, and could also be inconclusive some cases.2,3 For this rea-son, cystoscopy is associated in some cases with cytol-ogy1 in BC diagnostic and FU schedules as its
specificity (SP) reaches 98%.4 Cytology is a noninva-sive methodology but it has low sensitivity (SN), inter-observer variability, subjective evaluation, and low-accuracy in low-grade (LG) tumors.5
Over the last decades, many studies have attempted to identify urinary biomarkers that could replace cystos-copy. In fact, several urinary biomarkers have been reported in the literature and some of them are even Food and Drugs Administration FDA-approved, but none of these tests have been incorporated into routine clinical practice due to their insufficient diagnostic performance.6