Insights from ASCO GU 2026: Evolving Treatment Strategies in Bladder Cancer
Key Points
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Perioperative enfortumab vedotin (EV) plus pembrolizumab (pembro) may redefine the standard of care for muscle-invasive bladder cancer (MIBC) based on strong pathologic complete response (pCR) data and encouraging survival results.
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Bacillus Calmette-Guérin (BCG) combined with immunotherapy may expand treatment options for selected patients with very high-risk non–muscle-invasive bladder cancer (NMIBC). However, the benefit appears modest, and toxicity must be carefully considered.
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As EV plus pembro moves into earlier disease settings, optimal sequencing after recurrence remains uncertain; platinum chemotherapy and biomarker-driven therapies remain key options.
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Increasing use of antibody-drug conjugates (ADCs) requires greater attention to toxicity management, particularly neuropathy, rash, and metabolic complications.
Emerging data may soon influence bladder cancer treatment algorithms and clinical decision-making in community practice. During a panel discussion at the 2026 ASCO Genitourinary Cancers Symposium, bladder cancer experts shared insight on key findings from the conference.
Non–Muscle-Invasive Bladder Cancer: Options Beyond BCG
For decades, intravesical BCG has remained the cornerstone of therapy for high-risk NMIBC. Recent trials evaluating combinations of BCG with immune checkpoint inhibitors suggest modest improvements in event-free survival compared with BCG alone, although the benefit must be weighed against added toxicity.
A key takeaway from the discussion was that these regimens are unlikely to replace BCG as universal first-line therapy. Instead, they may provide an additional option for carefully selected patients with very high-risk disease, particularly those who might otherwise be recommended cystectomy but still wish to pursue bladder preservation.
Another important consideration is the real-world impact of introducing systemic therapy into NMIBC management. Because many of these patients may never develop metastatic disease, exposing all patients to systemic immunotherapy could represent overtreatment. As a result, patient selection and shared decision-making remain essential when considering BCG plus immunotherapy strategies.
Muscle-Invasive Disease: EV PlusPembrolizumab Moves Earlier
One of the most notable discussions focused on perioperative treatment for MIBC. New data evaluating EV plus pembrolizumab in the perioperative setting generated considerable interest, with many viewing the regimen as a potential new standard of care.
Historically, cisplatin-based chemotherapy has been the preferred neoadjuvant approach for eligible patients. However, EV plus pembro has demonstrated high activity across disease settings, including metastatic urothelial carcinoma. In the perioperative setting, the regimen achieved higher pCR rates than historical cisplatin-based regimens, reinforcing its potential to shift the treatment paradigm.
Importantly, EV plus pembro should not be considered a toxicity-free alternative to chemotherapy. While it avoids platinum exposure, EV carries its own adverse effect (AE) profile. As the regimen moves earlier in treatment algorithms, clinicians will need increasing familiarity with monitoring and managing these toxicities.
Several clinical questions remain unanswered. For example, it is not yet clear whether all patients require the full adjuvant component of therapy after surgery, particularly those who achieve excellent pathologic responses. In addition, the applicability of these data to upper tract urothelial carcinoma remains uncertain.
ctDNA and Bladder Preservation: Promising but Still Investigational
Circulating tumor DNA (ctDNA) is emerging as a potentially valuable biomarker in bladder cancer, especially in the perioperative setting. The panel noted that ctDNA testing is increasingly being incorporated into clinical discussions when evaluating postoperative risk or considering continuation of adjuvant therapy.
However, experts emphasized that ctDNA should currently be viewed as a prognostic tool rather than a definitive guide for treatment decisions. While ctDNA positivity is associated with a higher risk of recurrence, the optimal way to incorporate this information into treatment algorithms remains uncertain.
Bladder preservation after systemic therapy was also discussed. Although complete responses on imaging, cystoscopy, and ctDNA testing can be encouraging, there is currently insufficient evidence to routinely omit cystectomy. Outside of clinical trials, radical cystectomy remains the standard approach for eligible patients. Observation may be considered in select frail patients who are poor surgical candidates, but broader adoption of bladder-preserving strategies will require prospective data.
Metastatic Disease: Sequencing Questions Emerge
As EV plus pembro moves into earlier disease settings, sequencing after recurrence is becoming more complicated. The optimal approach after perioperative EV plus pembro remains unclear.
In practice, platinum-based chemotherapy remains a reasonable option at recurrence, given its continued activity and familiarity. This approach also allows biomarker-directed therapies to be reserved for later lines of treatment.
Molecular testing plays an increasingly important role in this setting. Patients with FGFR3 alterations may benefit from FGFR inhibitors, while HER2-directed therapies such as trastuzumab deruxtecan offer another targeted option in select patients. As more targeted therapies become available, sequencing decisions will likely remain individualized.
Managing Toxicity in the Era of ADCs
As ADCs move earlier in the treatment paradigm, toxicity management becomes an increasingly important component of care. EV is associated with several notable AEs, including peripheral neuropathy, dermatologic toxicity, hyperglycemia, and ocular symptoms.
Early recognition and proactive management are critical to maintaining patients on therapy. Temporary treatment holds, dose reductions, and multidisciplinary collaboration with dermatology or endocrinology may be necessary in some cases. Rash can be particularly challenging when EV is combined with pembrolizumab, since distinguishing ADC-related toxicity from immune-related toxicity may not always be straightforward. Patient education also plays an essential role, as early reporting of symptoms can help prevent more serious complications.
Overall, the discussion highlighted how quickly bladder cancer treatment is evolving. As new therapies continue to enter earlier stages of disease, clinicians must balance promising efficacy data with careful patient selection, sequencing, and toxicity management.