During the consensus meeting, patient advocates successfully argued for a highly robust definition of "event-free survival." The final definition counts not just cancer recurrence, but also the need for any additional standard-of-care treatment—including intravesical therapy—as an "event," reflecting the patient's perspective on what constitutes a successful outcome.

Despite strong data favoring pre-surgical systemic therapy, a surgeon argues that many patients will continue to undergo surgery first. This is due to real-world factors like surgeons being the point of diagnosis, urgent symptoms requiring rapid intervention, and patient preferences to have the tumor removed immediately.

The practice-changing Keynote B15 trial showed strong efficacy for neoadjuvant EV-Pembro. However, about half of patients discontinued treatment due to side effects. This creates a clinical paradox: patients who complete the full regimen may be over-treated, while those who stop early due to toxicity may be under-treated, complicating patient management and counseling.

The excitement around new systemic therapies has already created a "Wild West" environment where patient and surgeon motivation for cystectomy has plummeted. This cultural shift is outpacing prospective data, raising concerns that patients are making major decisions outside of rigorous clinical trials.

While bladder preservation is a key goal, there is an unavoidable risk. Forgoing definitive local treatment like surgery means a subset of patients will not be cured by systemic therapy alone and will miss their opportunity for a potentially curative operation, a crucial ethical consideration.

With highly effective neoadjuvant therapies now available, the surgeon's role in muscle-invasive bladder cancer is evolving. They are moving from being the primary decider and treater to being a key manager of a 'perioperative bundle,' where their first goal is often to get patients to medical oncology for systemic treatment.

Clinical Complete Response (cCR), assessed by imaging and biopsy, is the primary endpoint for avoiding surgery in new trials. However, these tools are known to be unreliable, potentially missing up to 25% of residual post-mucosal tumors and leading to undertreatment.

The success of new treatments like immunotherapy and ADCs leads to more patients achieving a deep response. This high efficacy makes patients question the necessity of a radical cystectomy, a life-altering surgery, creating an urgent need for data-driven, bladder-sparing protocols.

With pathologic complete response rates approaching 67% in patients completing neoadjuvant EV-Pembro, a majority of cystectomies are now removing cancer-free bladders. This creates an ethical and clinical imperative to rapidly launch prospective trials to validate bladder preservation strategies and avoid overtreatment.