Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Sep 25;9(3):237-251.
doi: 10.3233/BLC-230043. eCollection 2023.

New Intravesical Agents for BCG-Unresponsive High-Risk Non-Muscle Invasive Bladder Cancer

Anastasios D Asimakopoulos  1 , Maxim Kochergin  2 , Gaia Colalillo  1 , Omar Fahmy  3 , Fahmy Hassan  4 , Markus Renninger  5 , Andrea Gallioli  6 , Pavel Gavrilov  6 , Georgios Gakis  7
Affiliations

New Intravesical Agents for BCG-Unresponsive High-Risk Non-Muscle Invasive Bladder Cancer

Anastasios D Asimakopoulos et al. Bladder Cancer. .

Abstract

Background: With the exception of the FDA-approved valrubicin and pembrolizumab, there are no standard second-line treaments for BCG-unresponsive high-risk non-muscle invasive bladder cancer (NMIBC).

Objectives: To provide a systematic review of the novel intravesically administered therapeutic agents for the salvage treatment of BCG-unresponsive NMIBC.

Methods: Online search of the PubMed, EMBASE and Web of Science databases was performed. The endpoints of this review were to evaluate the efficacy of the agents in terms of complete response rates (CR) and durability of CR, overall survival, recurrence-free survival and cancer-specific survival and to report on their toxicity profile. A search on Clinicaltrials.gov was performed to identify ongoing clinical trials.

Results: 14 studies were included in this review. The critical clinical need for the development of an effective, safe and durable intravesical drug for the salvage treatment of high-risk NMIBC seems to be met mainly by intravesical gene therapy; in fact, data support the FDA-approved nadofaragene firadenovec as a potentially important therapeutic advancement in this context. Promising results are also being obtained by the combination of N-803/BCG and by innovative drug delivery systems.

Conclusions: Considering the plethora of novel intravesical treatments that have completed phase II evaluation, one can reasonably expect that clinicians will soon have at their disposal new agents and treatment options for BCG-unresponsive NMIBC. In the near future, it will be up to the urologist to identify, for each specific patient, the right agent to use, based on safety, results and cost-effectiveness.

Keywords: BCG; bladder cancer; bladder instillations; intravesical instillations; non-muscle invasive bladder cancer.

PubMed Disclaimer

Conflict of interest statement

A.D.A., M.K., G.C., O.F., F.H., M.R., A.G., P.G. have no conflicts of interest concerning the manuscript. G.G. is an Editorial Board Member of this journal, but was not involved in the peer-review process nor had access to any information regarding its peer-review.

Figures

Fig. 1
Fig. 1
PRISMA flowchart.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. van Rhijn BWG, Burger M, Lotan Y, Solsona E, Stief CG, Sylvester RJ, Witjes JA, Zlotta AR. Recurrence and progression of disease in non–muscle-invasive bladder cancer: from epidemiology to treatment strategy. Eur Urol. 2009;56:430–42. - PubMed
    1. Pignot G, Baboudjian M, Lebacle C, Chamouni A, Lechevallier E, Irani J, Tillou X, Waeckel T, Monges A, Doisy L, Walz J, Gravis G, Mourey E, Duperron C, Masson-Lecomte A, Efficacy of hyperthermic intravesical chemotherapy (HIVEC) in patients with non-muscle invasive bladder cancer after BCG failure. World J Urol. 2023 Feb 22. doi: 10.1007/s00345-023-04332-z - DOI - PubMed
    1. Witjes JA. Management of BCG failures in superficial bladder cancer: a review. Eur Urol. 2006;49(5):790–7. - PubMed
    1. Catto JWF, Khetrapal P, Ricciardi F, Ambler G, Williams NR, Al-Hammouri T, Khan MS, Thurairaja R, Nair R, Feber A, Dixon S, Nathan S, Briggs T, Sridhar A, Ahmad I, Bhatt J, Charlesworth P, Blick C, Cumberbatch MG, Hussain SA, Kotwal S, Koupparis A, McGrath J, Noon AP, Rowe E, Vasdev N, Hanchanale V, Hagan D, Brew-Graves C, Kelly JD; iROC Study Team. Effect of robot-assisted radical cystectomy with intracorporeal urinary diversion vs open radical cystectomy on 90-day morbidity and mortality among patients with bladder cancer: a randomized clinical trial. JAMA. 2022;327:2092–103. - PMC - PubMed
    1. Yang LS, Shan BL, Shan LL, Chin P, Murray S, Ahmadi N, Saxena A. A systematic review and metaanalysis of quality of life outcomes after radical cystectomy for bladder cancer. Surg Oncol. 2016;25:281–97. - PubMed

Publication types

LinkOut - more resources