Novel intravesical therapeutics in the treatment of non-muscle invasive bladder cancer: Horizon scanning

Abstract

IntroductionNon-muscle-invasive bladder cancer (NMIBC) is a common and heterogeneous disease; many patients develop recurrent or progress to muscle-invasive disease. Intravesical drug therapy is a pillar in the current management of NMIBC; notwithstanding, Mitomycin C (MMC) and Bacillus Calmette-Guérin (BCG) have numerous limitations including international supply issues, and local and systemic toxicity. Here we review novel intravesical therapeutic options and drug delivery devices with potential for clinical use in the treatment of NMIBC.MethodsPubMed, ClinicalTrials.gov and Cochrane Library searches were undertaken. Systematic reviews, meta-analyses, randomised controlled trials, single-arm clinical trials and national/international conference proceedings were included.ResultsNovel intravesical drugs, including chemotherapeutic agents, immune checkpoint inhibitors, monoclonal antibodies and gene therapies, have demonstrated varying efficacy in the treatment of NMIBC. Current evidence for the majority of treatments is mostly limited to single-arm trials in patients with recurrent NMIBC. Various novel methods of drug delivery have also been investigated, with encouraging preliminary results supporting the intravesical delivery of hyperthermic MMC and MMC hydrogel formulations.ConclusionsNovel therapeutic agents and drug delivery systems will be important in the future intravesical management of NMIBC. As our understanding of the molecular diversity of NMIBC develops, molecular subtyping will become fundamental in the personalisation of intravesical treatments. Further randomised studies are urgently required to investigate the efficacy of novel intravesical treatments and novel regimens, in comparison to current standards-of-care, particularly in the context of international BCG shortages.

Mucoadhesive Thiolated Hyaluronic Acid/Pluronic F127 Nanogel Formation via Thiol–Maleimide Click Reaction for Intravesical Drug Delivery

“…However, the high recurrence rate and poor prognosis diminish the effectiveness of surgery. Intravesical instillation chemotherapy and immunotherapy following TURBT are the major clinically available approaches for reducing tumor recurrence. , However, the bladder permeation barrier prevents the adhesion and permeation of instilled drugs on the bladder mucosa resulting in short residence time, poor permeability, and low bioavailability of instilled drugs inside the bladder . Furthermore, the instilled drug solutions were diluted with urine and washed out of the bladder during urine excretion, necessitating repeated infusions of high doses of drugs.…”

Local Drug Delivery in Bladder Cancer: Advances of Nano/Micro/Macroscale Drug Delivery Systems

“…When cancer spreads to the submucosa or lamina propria, it is considered a T1-stage cancer, 2 of 26 defined as non-muscle-invasive cancer (NMIBC). NMIBC accounted for around 68-80% of all cases, with 42% in the Ta low-grade stage [1,[3][4][5]. When cancer invades the detrusor muscle, it is a T2-stage cancer (muscle-invasive bladder cancer, MIBC).…”

Local Drug Delivery in Bladder Cancer: Advances of Nano/Micro/Macro-Scale Drug Delivery Systems

“…When cancer spreads to the submucosa or lamina propria, it is considered a T1-stage cancer, defined as non-muscle-invasive cancer (NMIBC). NMIBC accounted for around 68–80% of all cases, with 42% in the Ta low-grade stage [ 1 , 3 , 4 , 5 ]. When cancer invades the detrusor muscle, it is a T2-stage cancer (muscle-invasive bladder cancer, MIBC).…”

“…Approximately 25 to 32% of patients with bladder cancer present with MIBC (from which about 8% had T4), and despite a lower prevalence, the radical cystectomy raises a lot of concerns regarding the risk of cancer-related mortality and compromised quality of life [ 3 , 5 ]. Many NMIBC cases are suboptimally managed and are associated with a high recurrence (occurring in up to 80%) and progression rate.…”

“…Many NMIBC cases are suboptimally managed and are associated with a high recurrence (occurring in up to 80%) and progression rate. Moreover, 40–50% of cases progress to MIBC, which carries a 5-year survival rate of only 27–50% [ 5 ]. Effective treatment at the T1 stage will avoid removal of the bladder and improve the quality of life.…”