Bladder Cancer
Bladder cancer is a malignant neoplasm originating from the epithelial lining of the urinary bladder. The disease arises due to the uncontrolled proliferation of urothelial cells, often driven by genetic mutations and exposure to carcinogens such as tobacco smoke, aromatic amines, and chronic inflammation. Pathogenesis involves a multistep process of genetic alterations, including mutations in oncogenes and tumor suppressor genes, leading to cellular dysregulation, impaired apoptosis, and increased proliferative signaling. Key molecular pathways implicated include FGFR3, TP53, and RB1. Health impacts of bladder cancer are significant, as patients may experience hematuria, dysuria, pelvic pain, and, in advanced cases, systemic symptoms such as weight loss and fatigue. The disease is associated with high morbidity due to frequent recurrences and the potential for progression to muscle-invasive or metastatic disease, which significantly worsens prognosis. Bladder cancer also imposes a considerable psychological and economic burden due to the need for lifelong surveillance and repeated interventions.
Urothelial carcinoma, also known as transitional cell carcinoma, is the most common type of bladder cancer, accounting for over 90% of cases in developed countries. It originates from the urothelial cells lining the bladder and can present as non-muscle-invasive or muscle-invasive disease. Tumors may be papillary (exophytic, projecting into the bladder lumen) or flat (carcinoma in situ). Urothelial carcinoma is characterized by its high propensity for recurrence and can progress to invade the muscularis propria or metastasize to distant organs.
Squamous cell carcinoma of the bladder arises from squamous metaplasia of the urothelium, typically in the context of chronic irritation or infection, such as long-standing catheterization or schistosomiasis. This type accounts for approximately 3–5% of bladder cancers in Western countries but is more prevalent in regions where schistosomiasis is endemic. Squamous cell carcinoma tends to be more aggressive and is often diagnosed at an advanced stage.
Adenocarcinoma of the bladder is a rare histological subtype, comprising about 1–2% of cases. It arises from glandular elements within the bladder, which may be of urachal, primary vesical, or metastatic origin. Adenocarcinoma is often associated with poor prognosis due to its tendency for early invasion and metastasis.
Small cell carcinoma of the bladder is a rare and highly aggressive neuroendocrine tumor, representing less than 1% of bladder cancers. It is characterized by small, round, densely packed cells with scant cytoplasm and high mitotic activity. Small cell carcinoma frequently presents with advanced disease and has a poor prognosis.
Sarcomatoid carcinoma is a rare variant of bladder cancer exhibiting both epithelial and mesenchymal differentiation. This biphasic tumor is highly aggressive, often presenting at an advanced stage with rapid progression and poor clinical outcomes.
Bladder cancer is the tenth most common cancer worldwide, with an estimated 573,000 new cases and 213,000 deaths annually. The disease predominantly affects older adults, with a median age at diagnosis of approximately 73 years. Incidence is significantly higher in males than females, with a male-to-female ratio of about 3:1. Geographical variation exists, with the highest rates reported in North America, Europe, and parts of Northern Africa. Established risk factors include tobacco smoking, which accounts for up to 50% of cases, occupational exposure to aromatic amines, chronic urinary tract infections, prolonged catheterization, and exposure to certain chemotherapeutic agents and radiation. The majority of cases (over 90%) are urothelial carcinomas, while squamous cell carcinoma and adenocarcinoma are less common. Five-year survival rates vary widely depending on stage at diagnosis, with non-muscle-invasive disease having a favorable prognosis and muscle-invasive or metastatic disease associated with significantly lower survival.
The diagnosis of bladder cancer is multifaceted, beginning with a thorough history and physical examination, focusing on symptoms such as painless gross hematuria, irritative voiding symptoms, and risk factor assessment. Urinalysis and urine cytology are initial non-invasive tests, with cytology providing moderate sensitivity and high specificity for high-grade tumors and carcinoma in situ. Cystoscopy remains the gold standard for diagnosis, allowing direct visualization of the bladder mucosa and biopsy of suspicious lesions. Transurethral resection of bladder tumor (TURBT) is performed for histopathological confirmation, tumor staging, and grading. Imaging studies, including ultrasound, computed tomography (CT) urography, and magnetic resonance imaging (MRI), are utilized to assess the extent of local invasion, lymph node involvement, and distant metastases. The American Joint Committee on Cancer (AJCC) TNM staging system is employed for clinical and pathological staging, while tumor grade is determined based on histological features. Additional diagnostic modalities, such as fluorescence in situ hybridization (FISH) and urinary biomarkers, may be used as adjuncts in selected cases.
A range of pharmacological agents is available for the treatment of bladder cancer. Inbakicept, nogapendekin alfa, and the combination product nogapendekin alfa inbakicept are utilized for their immunomodulatory properties in the management of this malignancy. Nadofaragene firadenovec is employed as a gene therapy agent designed to deliver therapeutic genetic material directly to bladder epithelial cells. Disitamab vedotin is an antibody-drug conjugate that targets specific tumor antigens to deliver cytotoxic agents to malignant cells. Tislelizumab and toripalimab are monoclonal antibodies that function as immune checkpoint inhibitors, enhancing the body's immune response against cancer cells. Isactuzumab govitecan and sacituzumab govitecan are antibody-drug conjugates directed against specific cellular targets, facilitating targeted cytotoxicity in neoplastic tissue. Erdafitinib is a selective inhibitor of fibroblast growth factor receptors (FGFRs), indicated for tumors harboring susceptible FGFR genetic alterations. Enfortumab vedotin is another antibody-drug conjugate that binds to nectin-4, a protein commonly overexpressed in urothelial carcinoma, delivering a cytotoxic payload to tumor cells. Avelumab and durvalumab are programmed death-ligand 1 (PD-L1) inhibitors that modulate immune checkpoint pathways, thereby promoting antitumor immunity in advanced or metastatic bladder cancer.
| Structure | Generic Name | CAS Registry Number | Molecular Formula | Molecular Weight |
|---|---|---|---|---|
| inbakicept (Rec INN; USAN); nogapendekin alfa (Rec INN; USAN); nogapendekin alfa inbakicept (Prop INNM; USAN); nogapendekin alfa inbakicept-pmln | 1622189-43-8 | |||
| nadofaragene firadenovec (Rec INN; USAN); nadofaragene firadenovec-vncg | 1823059-12-6 | |||
 | disitamab vedotin (Rec INN; USAN) | 2136633-23-1 | C68 H106 N11 O15 R S | |
| tislelizumab (Rec INN; USAN); tislelizumab-jsgr | 1858168-59-8 | |||
 | isactuzumab govitecan; sacituzumab govitecan (Prop INN; USAN); sacituzumab govitecan-hziy; sactuzumab govitecan | 1491917-83-9 | C73 H98 N11 O22 R S | |
| toripalimab (Rec INN; USAN) | 1924598-82-2 | |||
 | erdafitinib (Rec INN; USAN) | 1346242-81-6 | C25 H30 N6 O2 | 446.545 |
 | enfortumab vedotin (Rec INN; USAN); enfortumab vedotin-ejfv | 1346452-25-2 | C68 H106 N11 O15 R S | |
| avelumab (Rec INN; USAN) | 1537032-82-8 | |||
| durvalumab (Rec INN; USAN) | 1428935-60-7 |
Make Order
Experimental Scheme
Implementation
Conclusion
Solutions For Bladder Cancer
Alfa Cytology, a preclinical research solution provider, provides its clients with one-stop solutions to accelerate cancer therapeutics discovery and development.