ASCO GU 2026 / Bladder Cancer 03/14/2026

Ep. 3: Optimizing Perioperative ADC and Immunotherapy in Muscle-Invasive Bladder Cancer

Smiling man with beard wearing a white shirt, professional headshot, suitable for oncology or cancer research content, emphasizing healthcare and medical expertise. Rahul Gosain, MD, MBA Oncologist smiling in white coat, highlighting cancer research and treatment expertise, with a bow tie, in a bright medical setting. Rohit Gosain, MD A man in a navy blue suit with a white shirt and patterned tie, looking thoughtfully to the side against a plain gray background. Matt Galsky, MD A professional male doctor in a suit standing outdoors with trees in the background, smiling confidently. Sia Daneshmand, MD A professional male in a navy suit and red patterned tie, smiling confidently against a neutral background, representing healthcare or medical expertise. Chad Reichard, MD High-quality professional portrait of a confident woman in business attire, showcasing leadership and expertise in healthcare or corporate settings. Shilpa Gupta, MD

Key Points

  • Treatment tailoring based on toxicity, pathological response, and emerging biomarkers—eg, circulating tumor DNA (ctDNA)—may allow clinicians to modify or de-escalate perioperative therapy, optimizing outcomes while minimizing exposure.
  • Enfortumab vedotin plus pembrolizumab (EV-pembrolizumab) includes an antibody–drug conjugate (ADC), and clinicians should communicate clearly that this systemic therapy brings unique toxicities such as rash, neuropathy, diarrhea, and alopecia.
  • Sequencing in recurrent disease and integration with other systemic therapies remains under investigation. Clinical judgment and patient-specific factors guide whether retreatment is appropriate.

Antibody–Drug Conjugates and Perioperative Management

During a Clinical Insights session moderated by Rahul Gosain, MD, MBA, of the Wilmot Cancer Institute, and Rohit Gosain, MD, of Roswell Park Comprehensive Cancer Center, experts including Sia Daneshmand, MD, of the Keck School of Medicine of USC; Matt Galsky, MD, of Mount Sinai; Shilpa Gupta, MD, of Cleveland Clinic; and Chad Reichard, MD, of Urology of Indiana explored nuances of perioperative systemic therapy for muscle-invasive bladder cancer (MIBC). 

Emerging regimens, such as EV-pembrolizumab, use an ADC platform designed to deliver chemotherapy more selectively, but panelists emphasized that this approach remains systemic therapy with associated toxicities.

Common adverse events observed in perioperative trials include rash, neuropathy, diarrhea, and alopecia, differentiating EV-pembrolizumab from gemcitabine-cisplatin–based regimens. Panelists highlighted the importance of counseling patients about these effects and monitoring them carefully, particularly in community settings. For patients unable to complete planned neoadjuvant cycles, clinicians may adjust the regimen—dropping one component or modifying the dose—based on toxicity severity and timing without necessarily compromising outcomes.

Individualizing Therapy and Looking Ahead

Pathologic complete response rates from EV-pembrolizumab and durvalumab trials have prompted discussion of potential treatment de-escalation or ctDNA-guided strategies, though panelists agreed these approaches are not yet ready for standard practice. For patients achieving robust responses, questions remain regarding adjuvant therapy’s necessity and duration. Dr. Galsky noted that future biomarker-driven approaches may refine duration, helping balance efficacy and toxicity.

Additionally, treatment sequencing in recurrent disease depends on timing and prior exposure. Patients whose disease progresses while receiving therapy are unlikely to benefit from immediate re-treatment, whereas those whose disease progresses after stopping therapy may respond to a similar regimen.