Transitional cell carcinoma of the bladder (syn. urothelial carcinoma) makes up the majority of bladder cancers. Based on the extent to which the tumor has spread into the bladder wall, it can be categorized as non-muscle invasive (superficial, papillary) or muscle invasive (non-papillary). The most typical symptom, painless hematuria, calls for further cystoscopy investigation, especially in high-risk patients (smokers, workers exposed to carcinogenic chemicals such as aromatic amines, patients exposed to arsenic in water, radiation or cyclophosphamide therapy), whereas computed tomography and magnetic resonance imaging provide additional visualization and staging information.
Transitional cell carcinoma of the bladder (syn. urothelial carcinoma) (TCC) constitutes 90% of bladder cancers [1]. Depending on cancer penetration into the bladder wall muscle layer, it is categorized as non-muscle invasive (papillary) or muscle invasive (non-papillary). A majority of bladder TCC are non-muscle invasive on discovery. Being low-grade, this type of cancer has a better prognosis than the high-grade invasive type but is more likely to recur. However, without treatment, non-muscle invasive carcinoma will eventually progress into muscle-invasive type [1] [2].
In both men and women, the most widespread risk factor for developing bladder TCC is smoking [3]. The second major factor is workplace exposure to carcinogens, such as aromatic amines, polycyclic aromatic hydrocarbons, chlorinated hydrocarbons or heavy metals [4] [5]. Oral intake of arsenic is also associated with bladder cancer, with contaminated drinking water being the main source of exposure [6]. Iatrogenic causes of TCC include ionizing radiation and cyclophosphamide therapy [4].
Most patients with TCC display urinary signs and symptoms, predominantly painless hematuria. While usually visible, hematuria can sometimes be microscopic and intermittent, requiring repeated tests in order to be discovered. Additionally, patients can experience urgency or frequency of urination, in some cases accompanied by discomfort or pain. In advanced disease, flank pain, leg swelling or a palpable pelvic mass may occur; non-specific symptoms such as cachexia or bone pain may signal the presence of distant metastases [7].
Cystoscopy and bimanual examination are the golden standards for diagnosis in suspected bladder cancer. Aside from enabling tumor detection and visualization, cystoscopy provides an opportunity for biopsy of the observed abnormalities through all bladder wall layers. The obtained samples can give information on the cell type in addition to cancer stage and grade [8]. Difficulties arise in cystoscopic detection of carcinoma in situ (CIS), which is either invisible or mimics inflammation (appears in red-velvety flat patches) [9]. CIS can be detected through cytology analysis of voided urine. While urine cytology demonstrates high accuracy in diagnosis of CIS and high-grade lesions, its sensitivity is inadequate for low-grade malignancies, which yield too few cells per urine sample. Urine tumor marker analysis, such as fluorescence in situ hybridization (FISH) can increase sensitivity and specificity in TCC detection [10]. In the case of positive cytology, but negative cystoscopy findings, mapping biopsy along with additional diagnostic procedures (e.g. imaging) are recommended for investigation of CIS and upper urinary tract malignancies, respectively [9].
Imaging techniques, primarily computed tomography (CT) and magnetic resonance imaging (MRI) complement cystoscopy in the detection of carcinomas situated in bladder diverticula, disease staging (distinguishing invasive from non-invasive forms) and lymph node visualization [8]. MRI is superior in tumor staging, especially when contrast-enhanced, T2-weighted and diffusion-weighted techniques are combined [1] [11]. Shortcomings of CT and MRI include false positive and false negative findings due to small lymph nodes, reactive lymphadenopathy and variability in bladder wall thickening depending on the degree of bladder extension [1] [8]. [F-18]-Fluorodeoxyglucose positron emission tomography (FDG-PET) can be used for staging of pelvic lymph nodes, discovering distant metastases and differentiating the reactive from tumor tissue. Urinary excretion of FDG limits this method in the diagnosis of primary bladder TCC [12].
The exceptionally high recurrence rate of bladder TCC warrants periodic post-therapeutic surveillance, by using cystoscopy, urinary cytology (including FISH), FDG PET and other imaging techniques [1] [8] [10] [12].