Optimization of Nonmuscle Invasive Bladder Cancer Recurrence Detection Using a Urine Based FGFR3 Mutation Assay

Abstract

Introduction. The assessment of risk of recurrence and progression of bladder cancer (BC) is still rather difficult. We decided to check the rates of the changes mentioned above in the group of the Polish patients after a year-long observation and next to compare them with the results calculated in the Euro-pean Organisation of Research and Treatment of Cancer (EORTC) risk tables. Methods. The tested group consisted of 91 patients who underwent transurethral resection of bladder tumour (TURBT). When being diagnosed, 60 cases were in the pTa clinical stage, whereas 30 cases were in T1. The coexisting carcinoma in situ (CIS) was observed in four cases. On the basis of the scores obtained from the EORTC tables, the patients were divided into the groups of low, intermediate or high risk of disease recurrence and progression. Results. Recurrence was noticed in 23 patients (25%), while progression was observed in 11 patients (12.1%). The rate of the observed recurrences proved to be lower than it had been predicted in all the groups, except for one of the intermediate-risk group (score 1-4). Moreover, the rate of the progressions predicted according to the EORTC risk tables was higher in all the risk groups. Conclusions. It can be noticed that the rate of real recurrences is lower than expected, whereas the rate of the observed progressions is overestimated. Partly, it could be the result of using a relatively small group of patients for observation and applying a different method of treatment.

A 3-Plex Methylation Assay Combined with the FGFR3 Mutation Assay Sensitively Detects Recurrent Bladder Cancer in Voided Urine

“…This could probably be improved by analyzing more than one urine sample as we showed previously for the FGFR3 mutation assay (27). Another possibility would be to increase the analytical sensitivity of the assays.…”

“…Up to 80% of the pTa tumors have a mutation in the fibroblast growth factor receptor 3 (FGFR3) oncogene (25,26). We showed that a multiplex assay for the most common mutations was able to detect about 75% of tumors smaller than 1.5 cm and 100% if the tumors were larger than 3 cm (27). A great advantage of the FGFR3 assay is that as these mutations are extremely rare in normal cells, an assay to detect FGFR3 mutations has a specificity of 100%.…”

The Diagnostic and Prognostic Performance of Urinary FGFR3 Mutation Analysis in Bladder Cancer Surveillance: A Prospective Multicenter Study

“…Indeed, previous studies evaluating the accuracy of detecting FGFR3 mutations in voided urine in the context of the follow-up of patients after TUR showed an estimated sensitivity in the range of 0.58 to 0.66 in patients with an FGFR3 mutation in the primary tumor (9,13,16,17,30), with an apparent specificity of about 0.95.…”

“…Mutations in fibroblast growth factor 3 (FGFR3) are found in a large proportion of non-muscle invasive bladder cancers (12) and may M A N U S C R I P T A C C E P T E D ACCEPTED MANUSCRIPT 2 therefore represent useful biomarkers for the follow-up of patients with B-TCC. Ten different FGFR3 mutations have been described in bladder cancer and 4 mutations (S249C, Y375C, G372C, and R248C) account for 95% of mutated FGFR3 (13). It has been shown that urine-based FGFR3 mutation analysis can detect recurrence, although its sensitivity may be limited if samples have few tumor cells (13)(14)(15).…”

“…Ten different FGFR3 mutations have been described in bladder cancer and 4 mutations (S249C, Y375C, G372C, and R248C) account for 95% of mutated FGFR3 (13). It has been shown that urine-based FGFR3 mutation analysis can detect recurrence, although its sensitivity may be limited if samples have few tumor cells (13)(14)(15). Recently, several studies have evaluated the sensitivity and specificity of FGFR3 mutation analysis in voided urine for detection of recurrence of superficial bladder cancer (9,(16)(17)(18).…”