Following high response rates to systemic therapies like EV Pembro, using radiation for bladder preservation is now questioned. It may constitute overtreatment by radiating a now cancer-free organ, while providing no benefit for the systemic micrometastases that are the primary driver of mortality.

For bladder cancer patients with micrometastatic disease, the standard cystectomy requires a significant delay for the operation and recovery. This window may allow unseen metastases to progress, suggesting that upfront, effective systemic therapy is more critical for survival than immediate major surgery.

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.

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.

Expert consensus shows a major paradigm shift: perioperative systemic therapy (like EV-Pembro, scoring 2.9) is the undisputed standard for muscle-invasive bladder cancer. Approaches starting with cystectomy alone now score below 1.8, formally branding them as inferior options.

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.

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.

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.