A Comprehensive Review of Current Approaches in Bladder Cancer Treatment

Abstract

Bladder cancer is one of the most common malignant tumors of the urinary system globally. It is also one of the most expensive cancers to manage, due to the need for extensive treatment and follow-ups that often involve invasive and costly procedures. Although there have been some improvements in treatment options, the quality of life they offer has not improved at the same rate as other cancers. Therefore, there is an urgent need to find new alternatives to ease the burden of bladder cancer on patients. Recent discoveries have opened new avenues for the diagnosis and management of bladder cancer even though the clinical approach has largely remained the same for years. The decline in bladder cancer-specific mortality in regions that promote social awareness of risk factors and reduction of carcinogenic exposure demonstrates the effectiveness of such measures. New agents have been approved for patients who have undergone radical cystectomy after Bacillus Calmette-Guérin failure. Current best practices for diagnosing and treating bladder cancer are presented in this review. The review discusses radiation therapy, photodynamic therapy, gene therapy, chemotherapy, and nanomedicine in relation to non muscle-invasive cancers and muscle-invasive bladder cancers, as well as systemic treatments.

Figure 1

Stages of bladder cancer.

Figure 2

A schematic diagram illustrating the mechanism using PD-1 (programmed cell death-1)/PD-L1 (programmed cell death-ligand 1) immune checkpoint inhibitors in restoring T-cell functionality.

Figure 3

(A) In vitro drug uptake in bladder epithelial cell (BdEC) vs cancer cell (RT112). “Wash” represents the time of replacing the drug solution with complete media. (B) In vivo drug uptake in rat tumor and nontumor areas on day 7 of intravesical administration of HAL and prodrug solutions in the nontumor area and tumor area for PpIX, Rh-L-PTX, and Rh-L-SN-38, respectively. (C) Fluorescence intensity along the cut line from the luminal side to the muscle layer (360 μm). (D) Scatter plot showing in vivo efficacy with 635 nm laser with PpIX-PDT and prodrug (Rh-L-SN-38 and Mt-L-MMC) combination. (E) Mean ± standard deviation presented in panel D. Statistical significance was determined using a paired one-tailed t test with **P < 0.01 and * P < 0.05). Reprinted in part with permission from the refs (124) and (125). Copyright 2024, American Society for Photobiology.

Figure 4

(A) Evaluation of drug release of PTX/CS NSs in various pH conditions. (B) Bioluminescence images of mice from each treatment group were taken. (C) Statistical results after normalizing each mouse’s tumor bioluminescence to the initial flux. (D) Results of tumor volume in different groups of mice were also recorded (n = 4), *P < 0.05; ** P < 0.01; ***P < 0.001. Reprinted in part with permission from the ref (186). Copyright 2018, American Chemical Society.

Figure 5

(A) Synthesis scheme of HSA NPs. (B) Percentage cell viabilities of T24 cells incubated with different concentrations (Ce6: 0.625–10.0 μg/mL, NTZ: 1.225–19.6 μg/mL) of formulations, both with and without laser exposure. (C) Immunofluorescence images of tumor slices stained for hypoxia, blood vessels, and nuclei using an antipimonidazole antibody, red dye, and blue DAPI, respectively. (D) Semiquantitative analysis of tumor’s hypoxia status was conducted using ImageJ software. Data are presented as mean ± SD, with **p < 0.01 analyzed by Student’s t test. (E) Survival rate of mice evaluated after receiving different treatments showed statistically significant results (P < 0.05). Reprinted in part with permission from the ref (216). Copyright 2021, American Chemical Society.