An advisory panel split 50/50 on a two-year immunotherapy regimen but voted 7-to-1 for a one-year drug with similar efficacy. This reveals that for adjuvant therapies in non-metastatic cancer, halving the treatment duration and toxicity exposure can decisively shift the risk/benefit calculation in favor of approval.

Beyond efficacy, new therapies like bispecifics require significant institutional support. Clinicians need training for unfamiliar side effects like CRS, and facilities need resources like observation units and admission protocols, creating a steep implementation curve for clinical practice.

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.

Current bladder cancer trials often fail to differentiate between patients with primary resistance (never responded) versus acquired resistance (responded, then progressed). Adopting this distinction, common in lung cancer research, could help identify patient subgroups more likely to benefit from immunotherapy re-challenge and refine trial eligibility criteria.

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.

High relapse rates (~70%) in surgery-alone arms of recent trials suggest most patients with muscle-invasive bladder cancer (MIBC) already have micrometastatic disease. This reframes the disease, prioritizing early systemic therapy over immediate surgery to achieve control and potential cure.

While the TAR-200 gemcitabine-releasing device showed lower efficacy than systemic EV-pembrolizumab, its value proposition is logistical simplicity. As a treatment administered entirely by urologists in-office via cystoscopy, it offers a less complex and potentially less toxic alternative, making it an attractive option based on practice workflow rather than superior outcomes alone.

In high-risk non-muscle invasive bladder cancer (NMIBC), trials like CREST and POTOMAC show adding a systemic immune checkpoint inhibitor to BCG therapy introduces significant toxicity. The benefit is primarily in local control, which may not justify the risk, especially with other effective intravesical options available.

Despite data from kidney cancer showing immunotherapy re-challenge is often ineffective, oncologists admit to using it in urothelial cancer. This highlights a clinical conflict where the desire to use a powerful drug class outweighs the lack of supporting evidence, especially in specific, confusing patient scenarios.