Background: The treatment landscape for inoperable locally advanced and/or mUC has evolved with the availability of 1L immune checkpoint inhibitors (ICIs), including approval of avelumab maintenance. However, the real world decision-making process for 1L regimens is not well defined. Methods: We interviewed US oncologists and oncology nurses in academic and community-based practices. Semi-structured interviews were conducted in August 2020 to explore decision-making processes regarding 1L treatment choices for patients (pts) with mUC, including PD1/PD-L1 testing practices and treatment eligibility determinants. Thematic analysis was used to identify clinical considerations associated with 1L treatment decisions. Results: 18 oncologists (mean age, 51.3 [SD, 9] years; 11% women, 55% >15 years in practice, 39% academic) and 18 oncology nurses (mean age, 43.8 [SD, 11.1] years; 94% women, 34% >15 years in practice, 50% academic) participated. Providers preferred platinum-based regimens in the 1L setting, specifically cisplatin-gemcitabine (cis-gem) and carboplatin (carbo)-gem. Eligibility for platinum-based regimens is typically assessed using clinical criteria, such as neuropathy, ototoxicity, poor kidney function, and performance status (PS). Providers noted that cis-based therapies have a greater risk of tolerability issues than non-cis-based 1L regimens. Oncologists recommended 4- 6 cycles of 1L chemotherapy and assessing response or progression after 2- 4 cycles. Across practice settings, providers described a shift to earlier and widespread use of PD-L1 testing to inform initial and/or future treatment decisions. Oncologists recommended 1L ICI monotherapy (approved for cis-ineligible pts with PD-L1+ expression status) for pts who may not tolerate chemotherapy well, including pts who are elderly, frail, and have poor PS or comorbidities. Practitioners used clinical guidelines, especially NCCN, and consider pt preferences and goals when making treatment recommendations, accounting for overall survival, quality of life, and durable response. Conclusions: Consistent with NCCN guidelines, practitioners reported use of cis-gem, carbo-gem, and ICIs as 1L regimens in pts with mUC, dependent on clinical factors. As the 1L mUC treatment pattern evolves with the adoption of avelumab 1L maintenance as the new standard of care and clinical trials test new approaches, future studies should evaluate changes in real world practice, including use of PD-L1 testing.