Challenges in Defining Clinical Complete Response to Systemic Therapy in Muscle-invasive Bladder Cancer: Insights from the EORTC STARBURST Project

: The standard of care (SOC) for treatment of muscle-invasive bladder cancer is neoadjuvant systemic treatment (NAT) with chemotherapy ± immunotherapy (pending durvalumab approval for this indication) followed by cystectomy or radiochemotherapy, regardless of the extent of any tumor response. Studies have recently begun to question the pertinence of local treatment in cases with a complete clinical response after NAT. However, such a de-escalation strategy is hampered by the poor correlation between clinical evaluation of the tumor response and final pathology results for radical cystectomy specimens. The aim of the EORTC STARBURST-1 trial is to develop and validate a multimodal assessment protocol to enhance prediction of the response to systemic treatment. This will include cystoscopy, multiparametric magnetic resonance imaging of the bladder, quantification of circulating plasma and urinary tumor DNA, and measurement of urinary biomarkers. If this protocol can be validated, it will be used in STARBURST-2 to randomize patients to either SOC or to NAT, followed by local treatment or a risk-adapted strategy according to the response to NAT. This strategy involves omitting local treatment and replacing it with intravesical or systemic treatments for complete responders, or with immediate systemic escalation in nonresponders.