How to guide the selection of patients for trimodality therapy: the case for tumor immune and stromal signature

Bladder cancer (BCa) is the 7th most common cancer in men, with an estimated 81,190 new cases and 17,240 deaths in 2018 in the USA (1). Radical cystectomy (RC) with cisplatin-based neoadjuvant chemotherapy (NAC) is the standard of care for the management of muscle-invasive BCa (MIBC). In recent years, bladder-preserving strategies combining bladder tumor transurethral resection (TURB) with radiotherapy and concurrent radio-sensitizing chemotherapy, also known as trimodal therapy (TMT), have shown similar results and reduced morbidity as compared to RC in selected MIBC patients (2,3). As a result, current guidelines now recommend both RC and TMT as effective treatment options for MIBC (4-7). TMT is underutilized by most practitioners (8), mostly because of the difficulty in identifying appropriate patients that might benefit from this treatment. Therefore, the identification of molecular biomarkers that can predict TMT outcomes to guide its selection as a therapeutic choice is of utmost importance.