Abstract IA006: Towards ctDNA-guided treatment of muscle-invasive bladder cancer

Abstract Cancer cells release cell-free DNA with tumor-specific molecular alterations into circulation, known as circulating tumor DNA (ctDNA). Numerous studies have underscored the biomarker potential of ctDNA in detecting minimal residual disease across various cancer types, including bladder cancer. The rapid clearance of ctDNA from circulation, typically under two hours, makes it an ideal candidate for real-time monitoring of tumor burden following surgical interventions and throughout oncological treatments. For ctDNA measurements to be effectively incorporated into clinical decision-making, it is crucial to conduct ctDNA-guided intervention trials that demonstrate tangible clinical benefits. Current trials focusing on muscle-invasive bladder cancer (MIBC) are supported by recent exploratory sub-analyses of completed clinical trials, which have shown that ctDNA can effectively guide treatment decisions in this context. Beyond guiding adjuvant treatments, ctDNA holds potential for directing bladder preservation strategies, potentially in combination with urinary tumor-derived DNA (utDNA) measurements. The need for treatment de-escalation, such as in neoadjuvant chemotherapy (NAC), is underscored by the observation that a significant proportion of patients undergo treatments that result in considerable adverse effects without achieving pathologic response. Traditional decision-making in cancer treatment, largely reliant on imaging-based criteria like the Response Evaluation Criteria in Solid Tumors (RECIST), often does not adequately reflect the ultimate clinical endpoint of overall survival. A ctDNA-based measure that considers ctDNA dynamics during treatment could serve as a superior tool or complement to current strategies. In conclusion, ctDNA has demonstrated significant promise as a biomarker in both retrospective and prospective studies for risk assessment in MIBC. The clinical value of ctDNA-guided treatment will soon be determined by ongoing clinical trials (TOMBOLA, IMvigor011, MODERN). In my presentation I will address the potential clinical impact of ctDNA analyses, the technological aspects involved, how urine analyses may supplement these findings, and future directions in the field. Citation Format: Lars Dyrskjøt. Towards ctDNA-guided treatment of muscle-invasive bladder cancer abstract. In: Proceedings of the AACR Special Conference on Bladder Cancer: Transforming the Field; 2024 May 17-20; Charlotte, NC. Philadelphia (PA): AACR; Clin Cancer Res 2024;30 (10Suppl): Abstract nr IA006.