At the 2026 American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO GU), one of the world’s most prestigious meetings in genitourinary oncology, multiple landmark studies were presented that are reshaping clinical practice. Among them, advances in urothelial carcinoma (UC) stood out prominently. We had the privilege of interviewing Professor Michiel van der Heijden from the Netherlands Cancer Institute, who shared in-depth insights into the latest breakthroughs in UC, bladder preservation strategies, safety management, and future directions in precision treatment.
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Oncology Frontier: During this ASCO-GU congress, which breakthroughs in urothelial carcinoma impressed you the most? What emerging directions may reshape clinical practice in the coming years?
Dr. Michiel van der Heijden: The most striking progress in urothelial carcinoma reflects a major trend: the rapid expansion of antibody–drug conjugates (ADCs) combined with immune checkpoint inhibitors. In particular, regimens based on monomethyl auristatin E (MMAE)-containing ADCs have become a central focus.
Previously, the EV-302 study demonstrated that enfortumab vedotin (a Nectin-4–targeted ADC) combined with pembrolizumab significantly outperformed platinum-based chemotherapy in first-line metastatic urothelial carcinoma, establishing this combination as a new standard of care.
At this ASCO-GU meeting, the EV-304 study further extended this paradigm into the perioperative setting for muscle-invasive bladder cancer (MIBC). The results confirmed that the combination of enfortumab vedotin plus pembrolizumab (EVP regimen) provides meaningful survival benefits when used before and after surgery, outperforming both upfront radical cystectomy and traditional cisplatin-based neoadjuvant chemotherapy.
One important unanswered question remains: do all patients need the full course of perioperative treatment, especially adjuvant therapy? This will be a key research direction moving forward.
Perhaps even more exciting is the progress in bladder preservation. For decades, avoiding radical cystectomy while maintaining oncologic control has been a major goal. The EVP regimen has achieved very high pathological complete response (pCR) rates—over 55% in the intention-to-treat population—providing a strong foundation for bladder-sparing strategies.
Currently, two main approaches are being explored. One is to identify patients who achieve clinical complete response (cCR) and potentially omit further consolidation therapy. However, local recurrence remains a concern.
To improve patient selection, we have learned that circulating tumor DNA (ctDNA) alone is insufficient. At this meeting, I presented urinary tumor DNA (utDNA) data from the phase III NIAGARA trial. ctDNA better reflects systemic disease risk, while utDNA is more accurate for detecting residual bladder lesions. Combining both significantly improves prediction of pCR and helps identify patients suitable for safe bladder preservation.
We also presented results from the INDIBLADE trial, a phase II study evaluating dual immunotherapy (ipilimumab plus nivolumab) followed by chemoradiotherapy. This approach achieved a 2-year bladder-intact event-free survival rate of 78%, with manageable safety. ctDNA clearance also emerged as a promising biomarker. This model suggests that induction plus consolidation therapy may allow more patients to safely preserve their bladder.
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Oncology Frontier: With these novel regimens, what are the key considerations for safety management and clinical implementation?
Dr. Michiel van der Heijden: The perioperative EVP data show generally good tolerability, even in cisplatin-eligible patients. About 25% of patients did not complete the full course, mainly due to intolerance to prolonged enfortumab vedotin exposure. However, we currently lack evidence that incomplete treatment compromises outcomes.
Importantly, the toxicity profile of ADC plus immunotherapy differs significantly from traditional chemotherapy. Peripheral neuropathy is one of the most common and clinically relevant adverse events associated with enfortumab vedotin, directly impacting quality of life.
Given that perioperative treatment may last up to six months, careful monitoring is essential. This also highlights the urgent need for treatment de-escalation strategies—reducing toxicity while maintaining efficacy. Although EVP represents the current cutting-edge standard, optimizing duration and intensity of therapy remains a key future goal.
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Oncology Frontier: Looking ahead, what are the most urgent scientific questions in advanced urothelial carcinoma?
Dr. Michiel van der Heijden: The central challenge is how to personalize treatment intensity.
With EVP therapy, many patients achieve deep remission. Meanwhile, our ability to assess disease status is improving rapidly through tools such as ctDNA, utDNA, and multiparametric MRI (mpMRI).
The future lies in integrating these tools to guide individualized treatment:
Patients with deep remission and no detectable disease may safely omit further intensive therapy. Patients with only local residual risk may benefit from localized consolidation, such as radiotherapy, avoiding unnecessary systemic treatment. Patients with persistent ctDNA positivity, indicating high systemic relapse risk, may require early treatment escalation or regimen changes.
This risk-adapted approach represents the future of urothelial carcinoma management. However, unmet needs remain—especially for patients who do not respond to current therapies. Developing more effective and less toxic treatments continues to be a priority.
Expert Profile
Michiel van der Heijden Netherlands Cancer Institute
Professor van der Heijden is a leading expert in urothelial carcinoma, with major contributions to clinical trials shaping modern treatment strategies, particularly in ADC and immunotherapy combinations. His work has played a key role in advancing precision oncology and bladder preservation approaches.
