Andrea Apolo, MD, outlines the impact of NIAGARA in the MIBC space

In this video, Andrea B. Apolo, MD, highlighted the practice-changing impact of the NIAGARA trial (NCT03732677), which evaluated the addition of durvalumab to perioperative cisplatin-based chemotherapy in patients with muscle-invasive bladder cancer (MIBC). Unlike prior studies of adjuvant nivolumab or pembrolizumab that targeted only high-risk patients, NIAGARA enrolled all patients with MIBC. The results demonstrated not only event-free survival improvements but also an overall survival benefit, establishing a new standard of care. Apolo emphasized that earlier data had hinted at immune checkpoint inhibitor (ICI) activity in the neoadjuvant setting, but the additive benefit had not been confirmed until now. However, she cautioned that the regimen represents a substantial treatment burden, underscoring the need to refine patient selection and determine who truly requires this intensive approach.

Turning to circulating tumor DNA (ctDNA), Apolo described it as a promising but still evolving tool for guiding adjuvant therapy. In the US, the Natera platform is already used in MIBC to help detect recurrence earlier than imaging alone. Yet significant challenges remain. When ctDNA levels rise without radiographic evidence of disease, clinicians face uncertainty about whether to initiate systemic therapy early—a strategy not yet supported by data. Apolo currently reserves treatment decisions for when disease is visible on imaging, though she acknowledges the clinical dilemma this creates.

Encouragingly, multiple prospective trials are underway to clarify ctDNA’s role. She pointed to the IMvigor011 study (NCT04660344), which stratified adjuvant atezolizumab (Tecentriq) use by ctDNA status. Early findings showed ctDNA-negative patients fared well without additional therapy, whereas ctDNA-positive patients derived benefit from adjuvant treatment. Although detailed results are pending, these trials represent a crucial step toward integrating ctDNA into routine practice. Apolo concluded that ongoing research will be essential to optimize both ICI sequencing and biomarker-driven therapy selection in bladder cancer. Apolo is acting deputy chief of the Genitourinary Malignancies Branch of the National Cancer Institute Center for Cancer Research, head of the Genitourinary Malignancies Branch’s Bladder Cancer Section, and director of the Bladder Cancer and Genitourinary Tumors Multidisciplinary Clinic.

REFERENCE

1. Apolo AB, Saad A, Kydd AR, et al. Top advances of the year: Bladder cancer. Cancer. 2025 Aug 15;131(16):e70020. doi:10.1002/cncr.70020