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.

Achieving a pathologic complete response (path CR) in the bladder after neoadjuvant therapy is a marker of drug efficacy, not a signal to stop treatment. Because patients die from metastatic, not local, disease, a path CR should be seen as a reason to "double down" on the effective systemic therapy to eradicate micrometastases.

After failing to outperform chemoradiation in muscle-invasive disease, TAR-200 may be repositioned. Instead of a primary treatment, it could be used sequentially after an effective systemic therapy to control the high-grade, non-muscle invasive relapses that often occur in patients who achieve a major response and wish to preserve their bladder.

While new FDA-approved intravesical treatments like nadofaragene firadenovec and TAR-200 demonstrate high complete response rates initially, their effectiveness consistently diminishes over time. This highlights the ongoing challenge of achieving durable, long-term bladder preservation.

In the SURE-01 trial, nearly a third of patients declined radical cystectomy after strong responses to sacituzumab govitecan. This patient-driven decision highlights a significant, growing interest in bladder preservation, pushing the field to validate less invasive approaches for select patients.

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.

While new systemic agents dominate MIBC discussions, chemo-radiation remains a critical treatment, especially for patients unsuitable for radical cystectomy due to age or comorbidities. For these individuals, it offers a potentially curative, bladder-preserving alternative that avoids the high risks and sequelae of major surgery.

For muscle-invasive bladder cancer patients achieving a complete response to neoadjuvant therapy, a barrier to forgoing bladder removal is local relapse risk. Adding intravesical BCG could prevent these recurrences, making bladder preservation a more viable long-term strategy for these patients.

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.