Bladder cancer

Abstract

Bladder cancer is a global health issue with sex differences in incidence and prognosis. Bladder cancer has distinct molecular subtypes with multiple pathogenic pathways depending on whether the disease is non-muscle invasive or muscle invasive. The mutational burden is higher in muscle-invasive than in non-muscle-invasive disease. Commonly mutated genes include TERT, FGFR3, TP53, PIK3CA, STAG2 and genes involved in chromatin modification. Subtyping of both forms of bladder cancer is likely to change considerably with the advent of single-cell analysis methods. Early detection signifies a better disease prognosis; thus, minimally invasive diagnostic options are needed to improve patient outcomes. Urine-based tests are available for disease diagnosis and surveillance, and analysis of blood-based cell-free DNA is a promising tool for the detection of minimal residual disease and metastatic relapse. Transurethral resection is the cornerstone treatment for non-muscle-invasive bladder cancer and intravesical therapy can further improve oncological outcomes. For muscle-invasive bladder cancer, radical cystectomy with neoadjuvant chemotherapy is the standard of care with evidence supporting trimodality therapy. Immune-checkpoint inhibitors have demonstrated benefit in non-muscle-invasive, muscle-invasive and metastatic bladder cancer. Effective management requires a multidisciplinary approach that considers patient characteristics and molecular disease characteristics.

Fig. 1 |. Bladder cancer categories.

Bladder cancer can be categorized into grades, which is the cytological appearance of the urothelium, and stages, which are determined by the spread and depth of bladder wall invasion of the tumour. Non-invasive papillary carcinomas are classified as Ta disease, whereas urothelial carcinoma in situ is classified as Tis disease. All invasive urothelial cancers arise from either high-grade papillary carcinoma or urothelial carcinoma situ. Adapted from ref. , Springer Nature Limited.

Fig. 2 |. Global incidence of bladder cancer.

Global estimated incidence of bladder cancer in 2020 in men and women of all ages. Data are expressed as age-standardized rates (ASRs; adjusted to World Standard Population) to account for differing age profiles among regions. Data were obtained from GLOBOCAN 2020. Map was produced by the World Health Organization/International Agency for Research on Cancer (https://gco.iarc.fr/today).

Fig. 3 |. Global mortality of bladder cancer.

Global estimated mortality due to bladder cancer in 2020 in men and women of all ages. Data are expressed as age-standardized rates (ASRs; adjusted to World Standard Population) to account for differing age profiles among regions. Data were obtained from GLOBOCAN 2020. Map was produced by the World Health Organization/International Agency for Research on Cancer (https://gco.iarc.fr/today).

Fig. 4 |. Pathogenesis pathways.

Potential pathogenesis pathways to papillary non-muscle-invasive bladder cancer (NMIBC) and solid muscle-invasive bladder cancer (MIBC), including key genomic events, are shown (Tables 1 and 2). Solid arrows indicate pathways for which there is histopathological and/or molecular evidence. Dashed arrows indicate pathways for which there is uncertainty. Estimated time for tumour development is shown on the left. CIS, carcinoma in situ.

Fig. 5 |. Histopathology of bladder cancer.

Normal urothelium (part a) is defined by cellular polarization towards the luminal surface with individual cells relatively monotonous in appearance and containing open chromatin. Low-grade papillary urothelial carcinoma (part b) shows papillary cores, in this image cut in cross-section, lined by urothelium that remains relatively monotonous and polarized but with hyperchromasia of some nuclei. Non-invasive high-grade neoplasia in the bladder may be papillary (part c) or flat (part d) and demonstrates disorganization, nuclear enlargement, nuclear pleomorphism, and hyperchromasia. High-grade lesions have the potential to invade beyond the basement membrane and into the underlying bladder wall.

Fig. 6 |. Landmarks in understanding, diagnosis and treatment of bladder cancer.

This timeline shows seminal developments in bladder cancer, highlighting clinical, scientific and technical advances that have changed or will change clinical practice or scientific thinking in the field^,,,,,,,,,–. BCG, Bacillus Calmette–Guérin; MVAC, methotrexate, vinblastine, doxorubicin plus cisplatin; NAC, neoadjuvant chemotherapy; TCGA, The Cancer Genome Atlas; UC, urothelial carcinoma.