NIAGARA in the EV + IO Era / MIBC 07/26/2026

Ep. 2: Perioperative Muscle-Invasive Bladder Cancer: Interpreting pCR, Survival, and Treatment Selection

Professional portrait of a smiling man in a suit and tie, wearing glasses, against a white background, suitable for medical or healthcare-related content. Ashish M. Kamat, MD, MBBS, FACS Professional portrait of a man in a dark suit and blue tie, smiling confidently against a neutral background. David H. Aggen, MD, PhD Professional portrait of a female oncologist in a white lab coat, smiling confidently, representing expertise in cancer treatment and research. Alexandra Drakaki, MD, PhD Comprehensive cancer research updates and oncology news from OncUpdates to stay informed on latest treatments, clinical trials, and breakthroughs in cancer care. Raji Shameem, MD

Key Points

  • While pathologic complete response (pCR) is an important early indicator of treatment activity, overall survival (OS) and event-free survival (EFS) remain the most clinically meaningful end points for perioperative muscle-invasive bladder cancer (MIBC).
  • Experts emphasized completing protocol-directed perioperative therapy, including adjuvant treatment when appropriate, and continuing to recommend radical cystectomy despite favorable pathologic responses.
  • Community oncologists are rapidly adopting newly approved perioperative regimens because they are already familiar with durvalumab and with enfortumab vedotin (EV) plus pembrolizumab (pembro) from other disease settings.

In the second installment of a recent Clinical Insights discussion, Ashish M. Kamat, MD, MBBS, FACS, of The University of Texas MD Anderson Cancer Center, was joined by David H. Aggen, MD, PhD, of Memorial Sloan Kettering Cancer Center; Alexandra Drakaki, MD, PhD, of the University of California, Los Angeles; and Raji Shameem, MD, of Orlando Health, to discuss how clinicians should evaluate end points such as pCR, EFS, and OS when incorporating newly approved perioperative therapies into practice.

From a community oncology perspective, Dr. Shameem noted that adoption of perioperative regimens has been facilitated by familiarity with both durvalumab and EV plus pembro in other disease settings. Because EV plus pembro is widely used in metastatic urothelial carcinoma and durvalumab has established roles across multiple malignancies, many community oncologists are comfortable managing their associated toxicities. The panel also emphasized that NIAGARA’s inclusion of patients with moderate renal impairment and the option for split-dose cisplatin closely mirrors real-world practice, making the regimen broadly applicable outside academic centers.

A significant portion of the segment focused on the role of pCR as an end point. Dr. Aggen cautioned against placing excessive emphasis on pCR alone, noting that although it is an attractive early and objective measure of treatment response, it has not been formally validated as a surrogate for OS in MIBC. Differences in surgical technique, pathology review, and trial design can also influence reported pCR rates across studies. Instead, he emphasized evaluating perioperative regimens based on the totality of the evidence, including long-term EFS and OS outcomes, while recognizing that meaningful pathologic downstaging short of pCR can also substantially reduce recurrence risk.

The panel also addressed whether patients achieving excellent responses after neoadjuvant therapy should consider bladder preservation instead of radical cystectomy. Dr. Drakaki strongly supported adhering to the treatment protocols evaluated in clinical trials, stressing that surgery remains an essential component of curative therapy. Although ongoing studies are exploring bladder-sparing approaches guided by biomarkers such as circulating tumor DNA, the experts agreed that current level 1 evidence supports radical cystectomy following systemic therapy.