Bladder Cancer

For further information, see CMDT Part 39-18: Bladder Cancer

Essentials of Diagnosis

• Gross or microscopic hematuria

• Irritative voiding symptoms

• Positive urinary cytology in most patients

• Filling defect within bladder noted on imaging

General Considerations

• Second most common urologic cancer

• More common in men than women (3.1:1)

• Mean age at diagnosis is 73 years

• Risk factors: cigarette smoking, exposure to industrial dyes and solvents

Pathology

• Urothelial cell carcinomas: ∼90%

• Squamous cell cancers: ∼7%

• Adenocarcinomas: ∼2%

• Bladder cancer staging is based on the extent (depth) of bladder wall penetration and the presence of either regional or distant metastases

• Natural history is based on cancer recurrence and progression to higher stage disease. Both are related to cancer grade and stage

Symptoms and Signs

• Hematuria is the presenting symptom in 85–90%

• Irritative voiding symptoms in a small percent

• Masses detected on bimanual examination with large-volume or deeply infiltrating cancers

• Lymphedema of the lower extremities with locally advanced cancers or metastases to pelvic lymph nodes

• Hepatomegaly or palpable lymphadenopathy with metastatic disease

Laboratory Tests

• Urinalysis—hematuria; on occasion, pyuria

• Azotemia

• Anemia

Imaging Studies

• Ultrasound, CT, MRI show masses within the bladder

Diagnostic Procedures

• Urine cytology useful in detecting disease at initial presentation or recurrence

• Cytology very sensitive (80–90%) in detecting cancers of higher grade and stage

• Imaging done primarily for evaluating the upper urinary tract and staging

• Diagnosis and staging are by cystourethroscopy and tumor biopsy, as well as random bladder and, on occasion, transurethral prostate biopsies

• Transurethral resection of bladder tumor (TURBT)

• TURBT can be done under general or regional anesthesia

• Resection is done down to muscular elements of the bladder

Medications

• Patients with superficial cancers (Tis, Ta, T1) are treated with complete transurethral resection with selective use of a single dose intravesical chemotherapy immediately following resection

• The subset of patients with carcinoma in situ (Tis) and those undergoing resection of large, high-grade, recurrent Ta lesions or T1 cancers are good candidates for additional intravesical therapy

• Patients with more invasive (T2, T3) but still localized cancers require more aggressive surgery (radical cystectomy), or the combination of chemotherapy and selective surgery

• Patients with muscle invasive (T2 or greater) urothelial cell carcinoma should receive neoadjuvant systemic chemotherapy prior to radical cystectomy

• Intravesical chemotherapy

  • Immunotherapeutic or chemotherapeutic agents administered weekly for 6–12 weeks

  • Maintenance therapy after the initial induction regimen includes intravesical

    • Thiotepa

    • Mitomycin

    • Doxorubicin

    • Valrubicin

    • Bacillus Calmette-Guérin (BCG) instillation

  • BCG is the only agent effective in reducing disease progression

Surgery

• Transurethral resection is diagnostic, allows for proper staging, and controls superficial cancers

• Partial cystectomy is indicated in patients with cancers in a bladder diverticulum

• Radical cystectomy with urinary diversion—a conduit of small or large bowel

• Continent forms of diversion are available, improve quality of life

Therapeutic Procedures

• Radiotherapy: external beam therapy over a 6- to 8-week period

• Chemotherapy (systemic)

  • Cisplatin-based combination chemotherapy

  • Combination radiotherapy and systemic chemotherapy or surgery, radiotherapy, and systemic chemotherapy

• Immunotherapy

  • Anti-PDL1 immunotherapy with atezolizumab

  • Atezolizumab, FDA approved for urothelial cancers, is associated with response rates of 25–30% in locally advanced and metastatic bladder cancer

  • In many cases, the responses to this immunotherapy are durable

  • Additional checkpoint inhibitors have also been approved for patients with chemo-refractory disease

    • Pembrolizumab and nivolumab (anti-PD-1 agents)

    • Durvalumab and avelumab (anti-PDL1 agents)

    • Atezolizumab and pembrolizumab are now approved as first-line therapy in patients with metastatic disease (PDL-1 positive tumors) or cisplatin ineligible patients (regardless of PDL-1 status)

Complications

• Intravesical chemotherapy: side effects include irritative voiding symptoms and hemorrhagic cystitis

• Radiotherapy

  • Bladder, bowel, or rectal complications develop in about 10–15% of patients

  • Local recurrence is common (30–70%)

Prognosis

• About 50–80% of bladder cancers are superficial (Ta, Tis, or T1) at initial presentation

  • Lymph node metastases and progression are uncommon in such patients when they are properly treated

  • Survival is excellent at 81%

• 5-year survival of patients with T2 and T3 disease ranges from 50% to 75% after radical cystectomy

• Long-term survival for patients with metastatic disease at presentation is rare

When to Refer

• All patients should be referred to an urologist

• Refer when histologic diagnosis and staging require endoscopic resection of the cancer

• Metastatic urothelial cancer should be managed by a medical oncologist