The standard of care for nonmuscle invasive bladder cancer (NMIBC) is the transurethral resection of bladder tumor (TURBT), followed by a risk-adapted approach involving adjuvant intravesical chemotherapy or immunotherapy (IO) to reduce both tumor recurrence and progression rates.1 Particularly, for intermediate- and high-risk NMIBC, Bacillus Calmette-Guerin (BCG) is the standard adjuvant treatment. However, a non-negligible portion of patients continues to fail or is unable to complete the scheduled BCG treatment and, consequently, radical cystectomy (RC) is the only therapeutic option recommended.1 Thus, reliable bladder-sparing solutions are urgently needed to fulfill the request of a rapidly increasing number of BCG-unresponsive patients who aim to postpone or avoid RC without impairing their survival. In this context, following the encouraging results of immune checkpoint inhibitors (ICIs) both in localized and advanced bladder cancer, many clinical trials are testing ICIs and novel targeted treatments also for NMIBC.