Although randomized trials comparing initial radical cystectomy versus intravesical therapy for high-grade T1 bladder cancer are lacking, numerous studies demonstrate poor oncologic outcomes with intravesical therapy in patients with the aforementioned “highest-risk” features. The potential benefits of timely, upfront radical cystectomy need to be weighed against the risks associated with cystectomy, such as complications, morbidity, and decreased quality of life for any given patient. Several factors support early radical cystectomy in patients with highest risk NMIBC, including significant understaging of high-grade T1 tumors and increased risk of progression to muscle-invasive disease despite appropriate intravesical therapy. Up to 50% of T1 tumors are upstaged to T2 or greater at the time of radical cystectomy.89, 291-294 Factors associated with high risk of progression to muscle-invasion are high-grade T1 tumors with large tumor size, multifocality, associated CIS, LVI or prostatic urethral involvement, extent and depth of lamina propria invasion, as well as presence of subtype histologies, diffuse disease or tumor location in a site not amenable to complete resection.34, 37, 38, 104, 295-297 It is not clear if intravesical therapy alters the risk of progression in these highest-risk patients with NMIBC, and excellent oncologic outcomes are reported with immediate radical cystectomy.298, 299 In addition to the potential oncologic benefit, a recent prospective study (CISTO trial) examined patient-reported outcomes comparing those who underwent cystectomy versus next-line intravesical therapy for patients with recurrent high-grade NMIBC and found that quality of life was in many cases superior in patients who underwent cystectomy.263 Thus, despite the recognized morbidity of radical cystectomy, the Panel supports considering timely, initial radical cystectomy in this patient population. However, radical cystectomy with urinary diversion has considerable morbidity, including gastrointestinal, genitourinary, and infectious and wound-related complications totaling over 60% within 90 days of surgery, even in high-volume centers of excellence regardless of open versus robotic approaches.300, 301 Mortality after radical cystectomy is typically <5%,300 but may increase substantially in the elderly with 90-day mortality rates >10% in patients >75 years of age and almost 20% in octagenarians.302 Thus, the risks of radical cystectomy and urinary diversion must be weighed and balanced carefully against the risks of disease progression and potential loss of the opportunity for cure in high-risk patients.