Bladder cancer (BC) is the most common urinary tract cancer and a leading cause of mortality worldwide, with approximately 550,000 new cases and 160,000 deaths per year
[1]. The incidence of bladder cancer differs according to the geographical region considered: the age-standardized incidence (ASI) is one-third less in undeveloped with respect to high-developed countries. The World Health Organization (WHO) predicts a rise in cases and deaths for the near future due to increased life expectancy
[2].
BC encompasses a wide range of histologies: urothelial carcinoma (UC), which represent the majority (~90–95%) of bladder tumors, squamous cell carcinoma (SCC) (2–5%), adenocarcinoma (0.5–2%), and small cell carcinoma (<1%). BC’s risk factors include occupational factors, age, sex, race, socioeconomic status, personal health, diet, and infection by pathogens
[3][4][5]. BC tumors are divided into two classes depending on whether they invade the detrusor muscle (muscle-invasive bladder cancer, MIBC) or not (non-muscle-invasive bladder cancer, NMIBC). The first presents a higher risk of metastasis of lymph nodes or other organs but, fortunately, represents only 25% of diagnosticated BC cases
[2]. NMIBC generally involves the fibroblast growth factor receptor 3 (
FGFR3) mutation, producing cancer with a high recurrence rate but a low risk of progression. By contrast, MIBC and carcinoma in situ exhibit deletions or mutations of
TP53, RB transcriptional corepressor 1 (
RB1), erb-b2 receptor tyrosine kinase 2 or
PTEN, leading to metastatic cancer
[6]. A link between some of these genotypes and cell phenotypes was recently observed, leading to the result that cell lines associated with a low risk of progression present an activated oxidative metabolic state, while those associated with a high risk present a non-oxidative state and high glycolytic activity
[7].
Evaluation of patients suspected of having BC is performed using cystoscopy, an invasive endoscopic procedure performed with a flexible scope and with local anesthesia
[8]. Histological evaluation is required if reddish flat papillary or solid lesions are observed because benign conditions like inflammatory diseases can mimic BC. Trans Urethral Resection of Bladder Tumor (TURBT) or resection of the entire area is used to obtain information about the histology of tumors. In addition, an inspection of cells in the urine (cytology) can be performed to detect missed cancer. Cells with a malignant appearance indicate cancerous lesions in the bladder and warrant cystoscopy and histological investigation.