Impact of Molecular Androgen and Estrogen Response Scores on Outcomes Following Neoadjuvant Pembrolizumab in Muscle-Invasive Bladder Cancer
Abstract
PURPOSE: Androgen and estrogen influence bladder cancer pathogenesis, but their role in modulating treatment response, especially immunotherapy, remains unclear. This post hoc analysis of the PURE-01 trial evaluated the impact of androgen and estrogen signatures on outcomes in patients with muscle-invasive bladder carcinoma treated with neoadjuvant pembrolizumab followed by radical cystectomy.
EXPERIMENTAL DESIGN: Pretreatment transurethral resection of bladder tumor samples from 102 PURE-01 patients was analyzed using the Decipher Bladder whole-transcriptome assay to classify genomic subtypes. Hallmark androgen response (ARS), early estrogen response (ERS-early), and late estrogen response (ERS-late) scores were derived and visualized with boxplots. Subgroup differences were assessed using Mann-Whitney U, χ2, and Kruskal-Wallis tests. Event-free survival (EFS) was the primary endpoint, whereas pathologic response was the secondary endpoint. Cox proportional hazard models and Kaplan-Meier analyses evaluated the association of molecular scores with outcomes. Immune190 and FGFR3 signatures were also analyzed to explore their interactions with ARS and ERS.
RESULTS: Luminal subtypes had the highest ARS and ERS scores across molecular classifications. Negative correlations were observed between Immune190 scores and ERS and ARS scores. ERS-late scores were highest in nonresponders and significantly associated with worse EFS. Conversely, ARS was not significantly linked to EFS.…
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