Two Onc Docs, hosted by Samantha A. Armstrong, MD, and Karine Tawagi, MD, is a podcast dedicated to providing current and future oncologists and hematologists with the knowledge they need to ace their boards and deliver quality patient care. Dr Armstrong is a hematologist/oncologist and assistant professor of clinical medicine at Indiana University Health in Indianapolis. Dr Tawagi is a hematologist/oncologist and assistant professor of clinical medicine at the University of Illinois in Chicago.

In this episode, OncLive On Air® partnered with Two Onc Docs to provide a comprehensive review of localized bladder cancer, covering everything from initial histology to the rapidly evolving treatment paradigms for muscle-invasive disease. Drs Armstrong and Tawagi emphasized that although urothelial carcinoma remains the most common bladder cancer histology, recognizing variants like squamous, adenocarcinoma, and small cell is vital, as they often require surgery-first approaches or specialized chemotherapy. A critical diagnostic pearl highlighted for oncology boards was the necessity of muscularis propria in the transurethral resection of the bladder tumor (TURBT) specimen. If muscle is absent, a repeat TURBT is mandatory to ensure the cancer is not under-staged. For non–muscle-invasive bladder cancer, the treatment goal is preventing recurrence and progression. Patients with high-risk disease should receive BCG induction and maintenance. For those who are BCG unresponsive, Drs Armstrong and Tawagi discussed several novel intravesical therapy options that may be preferred over systemic pembrolizumab to avoid toxicity.

The management of muscle-invasive bladder cancer (MIBC) is primarily dictated by cisplatin eligibility, which is determined by performance status, renal function, and the absence of neuropathy or hearing loss. In cisplatin-eligible patients, the phase 3 NIAGARA trial (NCT03732677) results led to a new standard of care (SOC), which is the addition of durvalumab (Imfinzi) to a gemcitabine/cisplatin backbone. Furthermore, the phase 3 KEYNOTE-B15 trial (NCT04700124) data demonstrated that neoadjuvant enfortumab vedotin-ejfv (Padcev) plus pembrolizumab (Keytruda) significantly improved overall survival compared with standard chemotherapy, though this combination is not yet the board-tested standard. For cisplatin-ineligible patients, the phase 3 EV-303 trial (NCT03924895) established neoadjuvant enfortumab vedotin plus pembrolizumab as a new SOC, replacing the previous approach of upfront cystectomy followed by adjuvant nivolumab (Opdivo).

Finally, Drs Armstrong and Tawagi discussed trimodal therapy as a bladder-sparing treatment approach. Ideal candidates for this approach must have small tumors, a complete TURBT, no hydronephrosis, and must commit to lifelong cystoscopic surveillance.