Abstract IA25: Molecular biomarkers of chemoradiation response in bladder preservation therapy

Abstract

Abstract The standard definitive treatment options for muscle-invasive bladder cancer are radical cystectomy or bladder-sparing trimodality therapy (TMT), consisting of maximal transurethral resection of bladder tumor followed by chemoradiation therapy. Although multiple series show these two treatment approaches have similar overall long-term outcomes, recent studies suggest that molecular biomarkers may identify subgroups of patients who may preferentially benefit from one type of therapy over the other. Such biomarkers include tumor-intrinsic genes involved in DNA repair and signal transduction, which confer sensitivity or resistance to radiation therapy based on the intrinsic biology of the tumor. Emerging biomarkers also include molecular signatures of the tumor microenvironment, suggesting an important role for tumor-extrinsic factors in governing therapeutic sensitivity or resistance. This presentation will review the evidence and rationale underlying potential prognostic and predictive molecular biomarkers in bladder preservation therapy. A specific focus will be on our recent gene expression profiling of 136 muscle-invasive bladder cancer patients treated with bladder-sparing TMT. Our analysis showed that higher immune infiltration was associated with improved disease-specific survival after TMT, whereas higher stromal infiltration was associated with shorter disease-specific survival in a comparison cohort treated with radical cystectomy after neoadjuvant chemotherapy. These findings require validation studies in additional cohorts, which are currently ongoing. An additional focus of the presentation will be on emerging liquid biopsy biomarkers of minimal residual disease after bladder cancer therapy. The standard follow-up for patients after bladder-sparing TMT includes cystoscopies with biopsies and imaging studies at regular intervals. Liquid biopsy approaches such as circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) may enable noninvasive monitoring of response and detection of minimal residual disease after therapy, with a substantial lead time over conventional follow-up approaches including imaging. If validated in prospective clinical trials, molecular biomarkers may guide the tailored selection of appropriate treatments for individual patients with muscle-invasive bladder cancer, as well as enable noninvasive monitoring of patients after therapy. Such biomarkers also have potential to guide the use of synergistic combinations of immunotherapy with chemoradiation therapy for bladder cancer. Citation Format: David T. Miyamoto. Molecular biomarkers of chemoradiation response in bladder preservation therapy [abstract]. In: Proceedings of the AACR Special Conference on Bladder Cancer: Transforming the Field; 2019 May 18-21; Denver, CO. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(15_Suppl):Abstract nr IA25.