AUA 2022: Frequency of Fibroblast Growth Factor Receptor Alterations and Association With Bacillus Calmette-Guerin Outcomes in a Real-World Genomic Analysis of High-Risk Non-Muscle-Invasive Bladder Cancer (GARNER) Study

( The 2022 Annual Meeting of the American Urological Association was host to a moderated poster session for non-invasive bladder cancer. Dr. Florus C. De Jong presented his own center’s real-world data evaluating the frequency of Fibroblast Growth Factor Receptor (FGFR) alterations in high-risk non-muscle-invasive bladder cancer (NMIBC) patients receiving BCG treatment and their associations with oncologic outcomes.


It has been established that Transurethral resection of bladder tumor (TURBT) followed by intravesical BCG induction with one to three-year maintenance is standard of care for high-risk NMIBC. To date, there are no reliable biomarkers to predict response to BCG. FGFR alterations frequently occur in this disease space, and their prognostic significance in this disease space remains unknown. In this real-world study, the authors retrospectively evaluated the frequency and predictive value of FGFR alterations in BCG-treated patients with high-risk NMIBC.


Whole-exome, whole-transcriptome sequencing or SNaPshot analysis was used to perform molecular profiling in patients with high risk NMIBC (HGTa, T1 or CIS) who underwent a TURBT followed by BCG at the Erasmus University Medical Center in Rotterdam, Netherlands.

An FGFR+ mutation was defined as at least one FGFR3 mutation (S249C, Y373C, R248C, G370C) and/or FGFR2/3 fusion (FGFR2-CASP7, FGFR2-BICC1, FGFR3-TACC3, and FGFR3-BAIAP2L1). The primary objectives included the frequency of FGFR alterations and their predictive value on recurrence-free survival with BCG treatment. The secondary objective was to assess the predictive value of FGFR alterations on PFS and DSS post-BCG. A two-side p-value <0.05 denoted statistical significance.

 This study included 594 pts with available FGFR alteration data. The mean age was 69.6 years and 79.5% were male. The prevalence of FGFR+ tumors was 180 (30.3%), of which 173 (29.1%) and 7 (1.2%) were FGFR3 mutations and FGFR2/3 fusions, respectively.


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There was no statistically significant difference in RFS between patients with and without FGFR mutations (HR: 0.74, 95% CI: 0.52-1.06, p=0.098). Multivariate analysis showed no association between FGFR status, sex, age, smoking status, tumor grade (WHO 1973), and CIS at TURBT on RFS rates.


With respect to PFS and DSS, there similarly was no statistically significant difference between FGFR+ and FGFR- patients (HR: 0.77, 95% CI: 0.54-1.10; HR 0.76, 95% CI: 0.46-1.27, p=0.30).


Among 174 pts with available FGFR alteration data at baseline and following BCG treatment,

FGFR alteration status was maintained post BCG for most patients (54 [31%] pts had FGFRalt pre vs 51 [29%] post BCG).
 The authors concluded that 30.3% of pts with high risk NMIBC have FGFR+ tumors. Patients with high risk NMIBC have similar outcomes post BCG regardless of FGFR status.

Presented by: Florus C. de Jong, MD, Erasmus MC Cancer Institute, Rotterdam, Netherlands

Written by: Rashid Sayyid, MD, MSc – Urology Chief Resident, Augusta University/Medical College of Georgia, @rksayyid on Twitter during the 2022 American Urological Association (AUA) Annual Meeting, New Orleans, LA, Fri, May 13 – Mon, May 16, 2022.