The emergence of positive data from trials like PATINA creates a dilemma for oncologists treating patients who are already stable on an older maintenance therapy. The consensus suggests not altering a successful regimen to avoid disrupting patient stability, revealing a cautious approach to integrating new evidence into established care.

In real-world practice, oncologists are granting treatment breaks, or 'holidays,' to metastatic bladder cancer patients who achieve major responses on enfortumab vedotin-pembrolizumab. This practice, driven by toxicity management and quality of life concerns, is common despite the lack of formal trial data to guide the optimal duration or timing of discontinuation.

Traditional non-inferiority trials for reducing treatment are difficult to fund and execute. A proposed paradigm shift is to use superiority trial designs, where the burden of proof is on demonstrating that a higher dose or longer duration of therapy is actually better than a de-escalated approach.

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.

Despite acknowledging that a one-size-fits-all treatment duration is suboptimal, the expert consensus is to follow the study protocol. This conservative, evidence-based approach prevails due to the absence of validated biomarkers, like ctDNA, to safely guide treatment de-escalation for individual patients.

Some oncologists are stopping guideline-supported perioperative treatment regimens early if a patient achieves a pathologic complete response (pCR) from neoadjuvant therapy alone. This practice is considered premature and risky, as data from dedicated de-escalation trials like VOLGA is not yet available to support it.

In early-stage bladder cancer, where the goal is a cure, the argument to "save a therapy for later" is flawed. The primary objective should be to use the most effective treatment upfront. Withholding it doesn't make it more effective upon relapse; it just gives the cancer an opportunity to progress.

New bladder-sparing trials mandate nine cycles of EV-Pembro to replicate the conditions of successful surgical trials. This conservative approach ignores that patient response is front-loaded while toxicity is back-loaded, likely overtreating many patients to ensure comparable efficacy.

A key lesson in bladder cancer is that patient attrition is rapid between lines of therapy; many who relapse from localized disease never receive effective later-line treatments. This reality provides a strong rationale for moving the most effective therapies, like EV-pembrolizumab, to earlier settings to maximize the number of patients who can benefit.