Bladder and Urothelial Cancer

Bladder and Urothelial Cancer

• Bladder and urothelial cancer are urological malignancies

Learning Outcomes

• Epidemiology and risk factors of urothelial cancer may be described
• The classification of urothelial cancer may be explained
• The clinical manifestations of urothelial cancer may be described
• The staging of urothelial cancer may be discussed
• Metastatic disease may be discussed
• Management and treatment options may be discussed

Epidemiology

• 2nd most common urological malignancy
• 4th most common cancer in men
• 10th most common cancer in women
• 3% of all cancer deaths
• UK incidence is 13,000 per year, with 4973 deaths
• Average age is the 8th decade and only 1% are less than 40 years
• Male to female ratio is 2.5:1

Risk Factors

• Smoking increases risk 2-5 fold, causing 30-50% of cases
• Gender (male) is a risk factor
• Age is a risk factor
• Occupational history with aromatic amine exposure is a risk factor
• Prior radiation (e.g., for prostate cancer) is a risk factor
• Long term catheter/SIC is a risk factor
• Schistosomiasis is a risk factor
• Drugs such as phenacetin/cyclophosphamide are risk factors

Classification of Urothelial Cancer

• 90% are Transitional cell carcinoma
• Can also be Carcinoma in situ
• Can also be Superficial (low grade vs high grade)
• Invasive classifications are also possible
• 7% are Squamous Cell Carcinoma
• 2% are Adenocarcinoma
• 1% are classified as Other

Clinical Manifestation

• Presentations of bladder cancer include painless visible hematuria in 80-90% of cases, which is considered cancer until proven otherwise
• Persistent microscopic hematuria may be present
• Consider older heavy smokers with recurrent UTIs and persistent storage LUTS as cases
• Clot colic may be present
• Advanced disease can manifest as lower limb swelling, pelvic/bone pain, or ureteral obstruction

Investigations/Diagnosis

• Standard hematuria work up needs to be performed
• Urinalysis
• Urine cytology
• Flexible cystoscopy
• CT TAP/Urography
• +/- MRI pelvis
• Differential diagnosis of haematuria includes Malignancy, Stones, Infection, Inflammation, Trauma, Renal/Nephrology causes, Other

Staging

• Tx: Primary tumor cannot be evaluated
• T0: No primary tumor
• Ta: Noninvasive papillary carcinoma
• Tis: Carcinoma in situ
• T1: Tumor invades connective tissue under the epithelium (surface layer)
• T2: Tumor invades muscle
• T2a: Superficial muscle affected (inner half)
• T2b: Deep muscle affected (outer half)
• T3: Tumor invades perivesical fat
• T3a: Tumor is detected microscopically
• T3b: Extravesical tumor is visible macroscopically
• T4: Tumor invades the prostate gland, uterus, vagina, pelvic wall, or abdominal wall
• Nx: Regional lymph nodes cannot be evaluated
• N0: No regional lymph node metastasis
• N1: Metastasis in a single lymph node <2 cm in size
• N2: Metastasis in a single lymph node >2 cm but <5 cm in size, or multiple lymph nodes <5 cm in size
• N3: Metastasis in a lymph node >5 cm in size
• Mx: Distant metastasis cannot be evaluated
• M0: No distant metastasis
• M1: Distant metastasis

Management of Localized Disease

• Superficial transitional cell carcinoma is managed with TURBT to remove the lesion and provide histology
• It also uses Intravesical chemotherapy with mitomycin C (reduces the risk of tumour recurrence but not disease progression)
• Carcinoma in situ:
• Use of Intravesical immunotherapy with BCG
• For 6 cycles of BCG as induction
• Followed by maintenance BCG for 3 years
• Invasive Transitional cell carcinoma:
• Neoadjuvant chemotherapy and radical cystectomy
• Radical radiotherapy is an option for patients who are unfit for cystectomy

Transurethral Resection Bladder Tumour

• It is Diagnostic and therapeutic
• Stages and grades disease
• Sample muscle to assess invasion
• Use Post operative instillation mitomycin C or epirubicin

NonMuscle Invasive Bladder Cancer (pTa/T1)

• May require repeat TURBT
• 30% tumours upgraded on repeat sampling
• EAU risk groups are classified and treated as followed:
  • Low: immediate instillation of intravesical chemotherapy after transurethral resection of the bladder (TURB).
  • Intermediate: one-year full-dose Bacillus Calmette-Guerin (BCG) treatment (induction plus 3-weekly instillations at 3, 6 and 12 months), or instillations of chemotherapy and one immediate chemotherapy instillation after prior TURB.
  • High: intravesical full-dose BCG instillations for one to three years or radical cystectomy (RC)
  • Very High: Consider RC and offer intravesical full-dose BCG instillations for one to three years to those who refuse or are unfit for RC.

Muscle Invasive Disease (≥pT2)

• Under 25% of bladder cancer presentations
• Can be suspected prior to TURBT based on tumour size, hydronephrosis, or fixed pelvis
• Local staging
  • CT TAP/Urogram
  • MpMRI - staged with VI-RADS score
• MIBC + Cystectomy is a morbid disease and treatment option

Muscle Invasive Disease (≥pT2) Treatment

• Radical Cystectomy + Pelvic Lymphadenectomy has a 5-year survival rate of 50%
  • Men: Cystoprostatectomy (Bladder, prostate, seminal vesicles
  • Women: Anterior exenteration (Bladder, urethra, uterus, ovaries, cervix, anterior vagina)
• Neoadjuvant chemotherapy improves OSS by 5-8% in 5 years
  • Cisplatin based chemo
  • only 20% actually complete NAC
• Urinary diversion procedure is also required
  • Ileal conduit most common in UK/ROI
  • Complications include UTI, pyelonephritis, ureteroileal leakage, stenosis, stomal complications, UUT changes
  • Orthopic neobladder is alternative

Muscle Invasive Disease (≥pT2) Treatment Options

• Bladder Sparing Treatments:
  • TURBT
  • External Beam Radiotherapy
  • Chemotherapy
  • Trimodality Treatment (TUR, EBRT, Chemo)
• Metastatic Disease:
  • Platinum-based chemo, first line
  • PD-1, PD-L1 inhibitors (Pembro, Atezolimab) approved in second line

Carcinoma-in-situ (pCIS)

• Is confined to epithelium
• Has an Intact basement membrane
• 50% present in isolation
• Has a poorer prognosis
• Has a Recurrence rate of 60-90%
• Diffuse CIS - 70% progress to muscle invasive disease
• Managed aggressively
• Treated with BCG
• Can offer upfront RC if necessary

Metastatic Spread

• Invasion of surrounding structures:
  • Peri-vesical fat and contiguous organs
  • Pelvic side wall
• Lymphatic:
  • Pelvic nodes
  • Para-aortic nodes
• Vascular:
  • Lungs
  • Bones
  • Liver
  • Brain

Functional Outcomes and Complications

• Vitamin B12 deficiency (17%)
• Metabolic acidosis
• Worsening of renal function
• Urinary infections
• Urolithiasis
• Stenosis of uretero-intestinal anastomosis
• Stoma complications in patients with ileal conduit
• Neobladder continence problems:
  • 66% women need to self catheterise
• Emptying dysfunction
• Increased fracture risk (21%)

Prognosis

• Confined: 60% 5YSR
• Nodes or local spread: 15-20% 5YSR
• Distant Mets: 0% 5YSR

Other Bladder Tumours

• Squamous cell carcinoma:
  • 5-7%
  • Develop without prior history
  • Rapidly growing aggressive tumours
  • Present as solitary, invasive and high stage
  • Predisposing factors: bladder diverticulae, chronic indwelling catheters, schistosomiasis (55-70%), bladder stones, chronic UTI

Adenocarincoma

• 2% of all bladder cancers
• 6th-7th decade, 2x more frequent in males
• Typically solitary- trigonal or urachal
• Most common tumour in exstrophy (congenital abnormality of bladder)
• Signet cell type infiltrative diffusely
• Make sure its not colorectal primary
• Treatment partial or total cystectomy