The bladder cancer landscape is evolving rapidly. The emergence of immune checkpoint inhibitors (ICIs) has fundamentally reshaped treatment, especially for muscle-invasive (MIBC) and advanced disease cases, and antibody-drug conjugates (ADCs) have introduced a new level of precision by targeting proteins like Nectin-4 commonly found on bladder cancer cells. The combination of these novel modalities is now producing much better outcomes — even in the perioperative setting for MIBC patients where chemotherapy used to be the main option, as we recently learned at the 2026 ASCO Genitourinary Cancers Symposium in San Francisco.
But as innovation accelerates, so does complexity. With a growing number of therapies entering clinical practice across disease stages, understanding real-world patterns — how treatments are sequenced, who responds, and where resistance emerges — has become critical. For life sciences companies, real-world data (RWD) offers a powerful lens to decode these dynamics, inform biomarker strategies, and guide more confident, value-driven investment decisions in an increasingly competitive space.
In this post, we highlight a few recent innovations and explore how high-fidelity RWD can bring greater clarity to decision-makers.
A perioperative paradigm shift in MIBC
For patients with MIBC or resectable locally advanced disease, the standard of care for more than two decades has been cisplatin-based neoadjuvant chemotherapy followed by radical cystectomy. That paradigm is now being challenged, with EV+P used in both neoadjuvant and adjuvant settings demonstrating superior outcomes and receiving approval from the FDA in November 2025 for cisplatin-ineligible MIBC patients.
Emerging evidence suggests the impact may extend well beyond that population. New data presented at ASCO GU this year showed that, in the perioperative setting, 79.4% of cisplatin-eligible MIBC patients treated with EV+P were event-free at two years, compared with 66.2% for those receiving chemotherapy. Complete response rates were also substantially higher (55.8% vs. 32.5%), with a consistent and manageable safety profile.
For the first time, a chemotherapy-free regimen appears to outperform cisplatin-based chemotherapy even in cisplatin-eligible patients. This represents the most significant shift in perioperative bladder cancer treatment in over 20 years — and positions EV+P as a likely future standard of care.
As adoption ramps up, new questions are emerging for life sciences companies:
- How rapidly are clinicians adopting EV+P in the perioperative setting?
- Are there disparities in access, and what factors are driving them?
- How is EV+P reshaping the neoadjuvant and adjuvant treatment landscape?
- Is increased use of EV+P translating into higher rates of bladder preservation?
- Which patients are most suited for this approach, and how influential is toxicity in decision-making?
A new standard for la/mUC — and new sequencing questions
Let’s start with the advanced disease setting, where enfortumab vedotin in combination with pembrolizumab (EV+P) has redefined the standard of care. The regimen has demonstrated markedly improved outcomes (including overall survival, progression-free survival, and objective response rates) compared with traditional chemotherapy in patients with untreated locally advanced or metastatic urothelial carcinoma (la/mUC). It is now the preferred first-line systemic treatment in this setting.
EV+P received accelerated approval from the U.S. Food and Drug Administration in 2023, driven in part by the urgent need for effective alternatives to platinum-based chemotherapy for patients unable to tolerate it due to comorbidities such as renal impairment, neuropathy, or overall frailty.
The approval of EV+P has significantly reshaped the first-line treatment landscape for advanced bladder cancer. Where treatment decisions were once largely split based on cisplatin eligibility, clinicians now have an effective option that can be used across patient groups. This has broadened the pool of patients who can receive a highly active regimen upfront and reduced reliance on traditional platinum-based chemotherapy as the default starting point. As a result, clinicians are rethinking how and when to use platinum-based regimens, and treatment sequencing strategies are beginning to shift.
This evolving landscape is introducing new complexity into treatment decision-making and raising critical questions for life sciences companies:
- What does real-world treatment sequencing look like today?
- To what extent does cisplatin eligibility still influence first-line treatment selection?
- What clinical or non-clinical factors are driving oncologists’ decisions to prescribe EV+P?
- How are second-line treatment patterns shifting in the post–EV+P era?
- Are patients discontinuing treatment prematurely? And if so, why?
Toward a more biomarker-driven future
At ASCO GU this year, new data also highlighted the growing role of circulating tumor DNA (ctDNA) in guiding treatment decisions for patients with MIBC, particularly when weighing active surveillance vs cystectomy post neoadjuvant therapy as well as if patients should receive adjuvant therapy or not. Interim results from a recent study suggest that ctDNA-positive patients experience poor outcomes regardless of whether they undergo surgery, while ctDNA-negative patients show similar metastasis-free survival whether managed with cystectomy or active surveillance. These findings raise a provocative possibility: ctDNA, measured through both serial plasma and urine assays,could help identify patients suitable for bladder-sparing strategies. In addition, ctDNA status may help refine decisions around adjuvant therapy, with ctDNA-positive patients potentially benefiting from treatment escalation, while ctDNA-negative patients may be candidates for de-escalation or observation.
In parallel, the advanced disease setting is seeing increased focus on HER2 as a therapeutic target, particularly for new antibody-drug conjugates like disitamab vedotin. This is highly relevant given that an estimated 60–80% of patients exhibit some level of HER2 expression.
Together, these developments underscore a more biomarker-driven future in bladder cancer and raise a new set of questions for life sciences companies:
- How common is HER2 testing in advanced bladder cancer today?
- What proportion of patients express HER2 across different levels?
- How are HER2-targeted ADCs likely to be sequenced alongside EV+P?
- What share of MIBC patients currently undergo ctDNA testing, and how frequently?
- How are ctDNA results influencing treatment decisions?
Reimagining intravesical therapy in NMIBC
The final area of innovation we’d like to point out is in intravesical drug delivery, particularly for patients with non–muscle invasive bladder cancer (NMIBC) where new device-enabled approaches are beginning to reshape the treatment landscape.
In 2025, the FDA approved two such therapies. One uses a reverse thermal hydrogel to maintain prolonged contact between a chemotherapy agent and the bladder lining, while the other relies on a pretzel-shaped device inserted via a standard catheter to facilitate sustained local drug delivery. Additional technologies are advancing in the pipeline, including intravesical systems designed to deliver targeted therapies such as FGFR inhibitors directly to the bladder, potentially reducing the systemic toxicities associated with oral administration.
Clinical outcomes to date have been particularly encouraging in patients with BCG-unresponsive disease, positioning these approaches as credible, non-surgical alternatives to repeat transurethral resection of bladder tumor (TURBT) procedures. As these options gain traction, however, developers need a clear understanding of real-world dynamics to fully realize their potential:
- What proportion of NMIBC patients are BCG-unresponsive?
- What are the typical next steps for patients who recur after BCG treatment?
- How is toxicity influencing the use of systemic therapies in this population?
- To what extent are urologists adopting intravesical, device-enabled therapies?
- Who is being tested for FGFR alterations?
Translating innovation into real-world insights
These are pivotal times in bladder cancer care. After decades of incremental progress, a new wave of therapies is not only improving outcomes but moving earlier in the disease continuum, when curative intent is still achievable. As the landscape continues to evolve, life sciences companies face a dual imperative: understand how these innovations are being adopted in the real world, and determine how to optimally position both emerging and established assets in an increasingly complex treatment paradigm.
To help research and commercial teams explore the questions raised throughout this piece — and uncover new insights beyond them — we developed the Panoramic dataset. It covers nearly 50,000 patients with bladder cancer and captures granular clinical detail, including neoadjuvant and adjuvant treatments , surgical and bladder sparing interventions, recurrence, cisplatin eligibility, as well as clinically meaningful subcohorts like HER2-positive and FGFR-altered patients. Outcomes data spans key endpoints such as pathologic complete response (pCR), resection status, real-world progression, and adverse events, alongside emerging biomarkers like ctDNA and PD-L1.
All data points are derived from electronic health records using advanced, in-house AI models and are systematically validated through a peer-reviewed quality framework, ensuring the level of fidelity required for high-stakes research and decision-making.
Connect with us at ASCO to learn how to turn evidence into smarter, faster decisions in bladder cancer.
