Plasmacytoid bladder cancer spreads locally along the urothelium, which can be missed on imaging. Clinicians must push for a thorough examination under anesthesia (EUA) before surgery, even if a patient shows a complete radiographic response to therapy.

In muscle-invasive bladder cancer, cisplatin ineligibility is frequently due to renal insufficiency caused by large, aggressive tumors obstructing the ureter. This redefines this patient group as having more advanced local disease, rather than simply being unfit for chemotherapy, explaining their poor outcomes with surgery alone.

With highly active agents yielding 30% complete response rates, the immediate goal should be to cure more patients by exploring potent combinations upfront. While sequencing minimizes toxicity, an ambitious combination strategy, such as ADC doublets, offers the best chance to eradicate disease and should be prioritized in clinical trials.

Treating 'non-clear cell' kidney cancer as a single entity is a major research limitation. Experts argue that distinct histologies like papillary and chromophobe are different diseases. Future progress requires dedicated, international trials for each subtype rather than grouping them due to rarity.

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.

In mixed histology bladder cancers treated with standard urothelial therapy, the variant component (e.g., squamous) is hypothesized to be the source of the resistant clone that emerges after treatment. This suggests post-progression biopsies are key to understanding resistance.

Even if a bladder tumor is predominantly a variant histology like squamous, the presence of any urothelial cancer component means it should be treated with the standard urothelial regimen (EV-Pembro). Pure variants without a urothelial element are treated differently.

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.

An expert oncologist identified a pathological complete response (pCR) rate over 50% as the benchmark that would fundamentally alter treatment. The EV Pembro trial's 57% pCR rate crossed this threshold, forcing a shift from a surgery-centric model toward bladder preservation strategies and systemic therapy.