There's a significant shift in urological practice where high-risk patients, such as an 80-year-old, are now often considered non-candidates for radical cystectomy due to the procedure's high morbidity. This change from the surgical side is a key driver for exploring bladder-preserving treatments like chemoradiation or novel systemic therapies.
Even as therapies like enfortumab vedotin (EV) become standard, clinicians express uncertainty about their efficacy in patients with variant histologies. Some variants exhibit low or no expression of nectin, the drug's target, raising concerns about treatment suitability and highlighting a critical knowledge gap where traditional platinum-based chemotherapy may still be preferred.
The development of TAR-210, an intravesical device delivering erdafitinib, exemplifies a key trend: achieving targeted therapy efficacy while avoiding debilitating systemic side effects. With a hundred-fold lower systemic drug absorption compared to its oral counterpart, this approach provides the "best of both worlds" for biomarker-driven, non-muscle-invasive bladder cancer.
Some clinicians are already using enfortumab vedotin plus pembrolizumab (EVP) for cisplatin-eligible patients off-trial, driven by promising early data and patient preference. This practice contrasts with a more "purist" approach of waiting for full trial results, highlighting a real-world tension between early adoption and strict adherence to evidence-based guidelines.
The upcoming Sunrise 3 trial is positioned to potentially replace BCG as the standard frontline intravesical therapy. Beyond superior efficacy, a key driver for this shift would be the chronic global BCG shortage and physicians' eagerness to adopt effective alternatives, mirroring the rapid adoption of new agents in the neoadjuvant setting.