Comparison of 2 new real‐time polymerase chain reaction–based urinary markers in the follow‐up of patients with non–muscle‐invasive bladder cancer

Abstract

BackgroundThe objective of the current study was to compare the diagnostic accuracy of 2 new real‐time polymerase chain reaction–based urinary markers with each other and with urinary cytology, cystoscopy, and/or histology in patients being followed for non–muscle‐invasive bladder cancer.MethodsA total of 487 patients were enrolled in the study. Patients were evaluated using voided urine cytology, the Xpert Bladder Cancer Monitor, the Bladder EpiCheck test, and white light cystoscopy.ResultsThe overall sensitivity was 27.17% for cytology, 64.13% for the Bladder EpiCheck test, and 66.3% for the Xpert Bladder Cancer Monitor. The overall specificity was 98.82% for cytology, 82.06% for the Bladder EpiCheck test, and 76.47% for the Xpert Bladder Cancer Monitor. The negative predictive value was very similar for the 3 tests at 83.56% for cytology, 89.42% for the Bladder EpiCheck test, and 89.35% for the Xpert Bladder Cancer Monitor. When combined, the Bladder EpiCheck test and Xpert Bladder Cancer Monitor detected overall 79.35% of the tumors: 70.37% in low‐grade and 92.11% in high‐grade tumors.ConclusionsThe Xpert Bladder Cancer Monitor and Bladder EpiCheck test were found to perform very well in terms of sensitivity. Together, the 2 tests detected approximately 92.11% of high‐grade tumors. Their specificity was high but could not reach the excellent value of cytology. The negative predictive value was the same for both tests and was higher than that for cytology, especially when the tests were used together (92.24%). These 2 new tests hold promise as urinary biomarkers. They may be used in combination to maximize sensitivity in a less invasive way, thereby reducing invasiveness in the follow‐up of patients with non–muscle‐invasive bladder cancer and decreasing discomfort for the patients as well as complications and costs.

The Bladder EpiCheck Test as a Non-Invasive Tool Based on the Identification of DNA Methylation in Bladder Cancer Cells in the Urine: A Review of Published Evidence

“…Seen in all studies, the sensitivity of cytology was lower than the BE sensitivity (Table 2), with percentages ranging from 27% [13] to 38% maximum [15]. Particularly, the cytology sensitivity was markedly low in low-grade NMIBCs (0-13% across studies), and increased, while remaining lower than BE sensitivity, in high-grade NMIBCs (50-67% across studies).…”

“…A subsequent study by the same authors [13] compared BE to another Real-Time Polymerase Chain Reaction-Based urinary marker (Xpert Bladder Cancer Monitor [18]), which measures the level of five target messenger RNAs, upregulated in urine samples from patients with bladder cancer. The study enrolled 487 patients, 55 of whom had an invalid BE (total population: 432 patients).…”

“…Finally, eight studies recruiting a total of 1993 patients met the inclusion criteria. All the studies were prospective, blinded, single-arm cohort studies, with five regarding multicentric tumors [ 10 , 11 , 12 , 13 , 14 ] and three regarding monocentric tumors [ 15 , 16 , 17 ].…”

“…One study was a secondary external independent analysis of the results of a previous one [ 11 ], a second study was an updated version of a previous one, with additional patients [ 14 ], and a third study was a comparative study on two types of Real-Time Polymerase Chain Reaction-Based (RT-PCR) urinary markers, based on the population analyzed in a previous study [ 13 ].…”

“…Patient follow-ups after BE varied from six months [ 17 ] to 12 months [ 11 , 12 , 13 , 14 , 15 , 16 , 17 ]. Follow-up data was not available from one study [ 10 ].…”