Treatment Approaches for Cisplatin-Ineligible Patients with Invasive Bladder Cancer.

OPINION STATEMENT: Cisplatin has been established as an important agent in the neoadjuvant setting prior to radical cystectomy (RC) surgery for muscle-invasive urothelial cancer (MIUC) as well as in the unresectable or metastatic urothelial carcinoma (mUC) setting. Unfortunately, many patients in practice are felt to be "cisplatin-ineligible." Thus, it is vital that we develop treatment approaches and novel therapeutics for this population. We evaluate therapeutic alternatives to cisplatin-based treatment. For patients undergoing RC, there is no recommended alternative to neoadjuvant cisplatin-based combination therapy, and upfront RC or clinical trials are preferable. For patients receiving "bladder-sparing" radiation, concurrent radiosensitizing chemotherapies may be used, and several trials are also underway. For cisplatin-ineligible patients with mUC who are eligible for chemotherapy, carboplatin-based or split-dose cisplatin-based regimens may be employed. Pembrolizumab and atezolizumab offer options as first-line therapy for cisplatin-ineligible patients with high PD-L1 expression. The results of trials combining checkpoint inhibitors or platinum-based chemotherapy plus PD1/PD-L1 inhibitors are eagerly awaited. For platinum or chemotherapy-ineligible patients with mUC, immune checkpoint inhibitors such as inhibitors of programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) are approved regardless of PD-L1 expression. However, given limited effectiveness of first-line PD-1/PD-L1 inhibitor monotherapy in tumors with low PD-L1 expression, trials in this space are critical.