Urothelial Carcinoma: Risk Factors and Development

• Urothelial carcinoma is a common urological malignancy
• It can start in the urinary tract, both upper and lower, but the bladder is the most common location

Bladder Cancer (90-95%)

• Bladder cancer ranks as the 7th most common in males and 10th in the general population
• Females with bladder cancer have a higher mortality rate, lower incidence, higher stage at diagnosis and have a worse prognosis
• Symptoms of the bladder cancer in women are often mistaken for urinary tract infections or cystitis

Epidemiology

• Bladder cancer is common in Europe and the US
• It's less common or less diagnosed in East Asia and Africa
• Mortality is relatively high overall

Risk Factors

• The most important and established risk factor is tobacco smoke
• Family history seems less relevant for bladder cancer
• Occupational exposure to aromatic amines and other compounds in factories is the second most important risk factor
• Schistosomiasis is a risk factor, especially in countries like Egypt
• Environmental pollution can increase the likelihood of bladder cancer
• Previous medical interventions in the pelvis, like secondary tumors due to radiation, increases the risk of developing bladder cancer
• Tobacco smoke accounts for an estimated 50% of bladder tumors
• Current smokers have a 4-fold higher risk of developing bladder cancer compared to nonsmokers
• Substances found in tobacco smoke cause bladder cancer and are excreted through the urinary tract, exerting a carcinogenic effect
• Workers who handle dyes, paint, metals, and petroleum products are at higher risk Occupational risk-related carcinogenic substances include aromatic amines, accounting for an estimated 10% of bladder cancers
• The impact of diet appears limited, although some studies link meat and vitamin supplements to bladder cancer, the topic is still controversial

Histology

• The most common type of bladder cancer and upper urinary tract tumor is urothelial carcinoma (90% of cases)
• Other cases that are not urothelial carcinoma are squamous cell carcinoma (presents with a meat-like appearance) and schistosomiasis is an important factor
• Tumors that are not part of the urothelium are adenocarcinoma, small cell carcinoma, sarcomatoid carcinoma and other rare tumors
• These account for about 1% of total cases

Diagnosis and Staging

• The most common symptom is haematuria, that can appear alone, or with lower urinary tract symptoms
• Imaging is performed using transabdominal ultrasounds (first-line testing) since it is cheap and non invasive - these can detect renal and intraluminal bladder masses and hydronephrosis
• CT urography requires a late-phase scan to highlight lesions
• The bladder is filled with contrast, and suspicious lesion can be seen
• It is the gold standard to diagnose muscle-invasive tumors of the bladder and to diagnose upper urinary tract carcinoma
• Intravenous urography involves injection of contrast media in veins.
• MRI is useful for staging of bladder cancer, but its role in this context is being still evaluated

Urinary Cytology

• Additional modality used for diagnosis
• Using voided urine or bladder washing specimens, pathologist looks for specific tumor cells
• Urinary cytology is very accurate in the detection of high grade tumors
• Sensitivity, specificity of urinary cytology is generally low, so tests are usually repeated multiple times
• Urine molecular tests are currently under evaluation, but their use is limited to investigation

Cystoscopy

• Allows detection of papillary tumors while identification of flat lesions can be challenging
• Can be performed before the CT scan
• Always consider patient's history and then use US, CT urography, cystoscopy and cytology to diagnose bladder cancer

Additional Detection Methods

• Narrow-band imaging and Photodynamic diagnosis, these improve the accuracy of cystoscopy in detecting flat lesions, but specificity decreases because lesions that are hypervasculaized but are not tumors
• NBI darkens hypervascularized lesions for detection
• TURBT is the standard first approach to BC and is diagnostic & therapeutic step

TURBT Method

• Collects specimens to confirm the tumor, local staging (how deep the tumor goes into the bladder wall) and grading
• Cystoscopy is performed with rigid instruments and a 'resection loop' is used to resect the lesion which is then analyzed by the pathologist
• It helps differentiate between Muscle-invasive bladder cancer and the non-invasive type

Staging

• Distinguishes MIBC from NMIBIC
• Tis is a synonym for CIS, representing a separate chapter for convenience, stages are considered to be Ta, T1, T2, T3, and T4
• Ta and T1 = superficial tumors
• T2 or higher = muscle-invasive tumor
• Staging also includes categories that highlight the presence of distant metastases and lymph node involvement

Tumor Grading Systems

• First system goes from 1 to 3
• Second system distinguishes between low-grade and high-grade tumors, where G1 = low grade, and G2 + G3 = high grade tumors
• CIS (Tis) = limited to the mucosa and high grade, with the potential to progress
• Second resection or re-TURBT is performed within 2-6 weeks if the first resection isn't macroscopically considered complete

Risk Group

• High indicators of recurrence: age, number of tumors, their size, prior recurrence rate, staging, presence of concurrent CIS and grade.
• Risk groups are Low, Intermediate, High and Vary High risk

Post TURBT

• Patient should cease smoking based on risk group classification
• Repeated instillations of chemotherapy (mitomycin, gemcitabine or pharmorubicin) can be offered
• High Risk Group uses BCG treatments - immediate radical cystectomy if high grade, not muscle-invasive
• Patients with Very High Risk tumors, immediate RC is recommended in addition to BCG.
• Therapeutic pathway for NMIBC is TURBT, adjuvant intravesical instillations (one shot or repeated) and cystectomy

Muscle-Invasive Bladder Cancer

• Reaches into the the detrusor muscle of the bladder
• Requires staging nodes and metastases with contrast enhances CT
• Gold standard for treatment is radical cystectomy with extended bilateral pelvic lymph node dissection

Other Facts

• If patient is fit for cisplatin-based chemotherapy and if their tumor is T2-T4a, cN0 M0 offer neoadjuvant chemotherapy

Surgical Procedures

• Incontinence: (unilateral/bilateral ureterostomy or ileal conduit)
• Continence: (ureterosigmoidostomy, heterotopic, or orthotopic neobladder)
• For metastatic bladder cancer, surgery is performed for salvage, otherwise treatment normally involves chemotherapy and immunotherapy

Upper Urinary Tract Tumors (5-10%)

• Involve ureters, and the pelvis/calyces of the kidney (in the urothelium, not the parenchyma)
• 17% of these cases have concurrent bladder cancer, upper the fact urinary tract imaging is performed following BC treatment
• Peak incidence in the eighth decade of life for both BC and UTUC
• UTUC can be linked to hereditary nonpolyposis colorectal carsinoma HNPCC otherwise know as lynch syndrome

Factors

• Common with that of BL risk and tobacco and occupational exposure are factors
• Presenting with haematuria always ask what their job is and if they are smokers
• Tobacco smoking is increased from 2.5 to 7

Histology and Presentation compared to BC

• Derived from urothelium, urethral sarcomas present as well
• Can be non invasive papillary tumors, flat lesions or muscle invasive carcinomas
• UTUCs are invasive and can be diagnosed at time of diagnosis unlike BC
• UTUC = aggressive than BC - 7% of people who have it have metastatic disease at presentation.

Symptoms and Diagnosis

• Diagnosis can be incidental due to detection of hydronephrosis though imaging
• CT Urography
• MRI
• Cystoscopy
• Urine cytology
• Diagnostic = ureteroscopy
• CT has over 70% lower % for UTUC, but specificity is higher
• A diagnosis can be achieved though CT Urography, MRI, Cystoscopy, Urine Cytology, diagnostic Ureteroscopy
• Ureteroscopy = permits tissue sampling though a flexible uroteroscope which is also a biopsy
• Laser ablation allows them to be small enough

Other Facts and Info

• Sampling of the muscle layer is almost impossible due to it being to thin
• A procedure used is radical nephroureterectomy = removal of entirely kidney and the ureter, including the part of the ureter that enters the wall of bladder

Explore the major risk factors contributing to urothelial carcinoma development, including the impact of tobacco smoke and other environmental exposures. Understand why females often present with advanced stages of bladder cancer. Learn about characteristics indicative of muscle-invasive bladder cancer.