Immune checkpoints inhibitors in the management of high-risk non-muscle-invasive bladder cancer. A scoping review

Abstract

Purpose: Provide the current state of trials investigating the effectiveness and safety of checkpoint inhibitors in patients with non-muscle invasive bladder cancer.

Methods: We conducted this scoping review following the recommendations of the Joanna Briggs Institute. We searched for MEDLINE, EMBASE, CENTRAL databases, and clinical trials in search engines such as clinicaltrials.gov and clinicaltrialsregister.eu. We included clinical trials in patients over 18 years of age diagnosed with high-risk non-muscle-invasive bladder cancer who suffer treatment failure with Bacillus Calmette-Guérin (BCG). Even those who have not received prior therapy. Those clinical trials also evaluated intravenous- or intravesical-administered immune checkpoint inhibitors and those associated with BCG.

Results: Thirteen clinical trials are currently being developed with immune checkpoint inhibitors as a therapeutic alternative in patients diagnosed with non-muscle-invasive urothelial carcinoma of the bladder. Five of these have not received prior therapy with bacillus Calmette-Guérin. The remaining eight studies in patients who received BCG immunotherapy with a poor response are classified as persistent, refractory, or non-responders to BCG therapy. Also, in patients who do not accept surgical management with radical cystectomy. Preliminary results from studies such as SWOG S1605 (NCT02844816) show encouraging antitumor activity and long-lasting response patients with carcinoma in situ with or without papillary disease in terms of disease-free survival and rate free of adverse events. Recently, Keynote-057 (NCT02625961) evidenced that after 36 months of follow-up, Pembrolizumab as monotherapy was tolerable and showed promising antitumor activity in patients with BCG-unresponsive non-muscle-invasive bladder cancer.

Conclusion: The checkpoint inhibitor response may offer a therapeutic alternative for patients diagnosed with high-risk non-muscle-invasive bladder cancer. However, the complete response rate documented in this scoping review is limited to patients with carcinoma in situ, with mild adverse effects, without reporting severity or death from the intervention.

Keywords: Atezolizumab; Bladder cancer; Bladder neoplasia; CTLA-4 blockers; Durvalumab; Immune checkpoint inhibitors; Ipilimumab; Nivolumab; Non-muscle invasive bladder cancer; PD-L1 inhibitor; PD1 inhibitor; Pembrolizumab or Keytruda.