Bladder Cancer

Essentials of Diagnosis

• Gross or microscopic hematuria

• Irritative voiding symptoms

• Positive urinary cytology in most patients

• Filling defect noted within bladder 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

• Both cancer grade and stage influence the natural history of bladder cancer including local recurrence within the bladder and progression to higher-stage disease

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 is done primarily for evaluating the upper urinary tract and for 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 non–muscle invasive 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 and/or T1 cancers are good candidates for additional intravesical therapy

• Patients with muscle invasive (T2+) but still localized cancers

  • Are at risk for both nodal metastases and progression

  • Require more aggressive treatment

  • Gold standard treatment is neoadjuvant chemotherapy followed by radical cystectomy, which confers a survival advantage versus cystectomy alone

  • This is particularly important for higher-stage or bulky tumors to improve their surgical resectability

  • Trimodal bladder preservation therapy can offer similar outcomes in optimally selected patients and consists of

    • Complete TURBT

    • Sensitizing systemic chemotherapy

    • External beam radiotherapy

    • 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

• TURBT 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 results in partial or complete responses in 15–45% of patients and is the preferred approach

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

• Immunotherapy

  • FDA-approved anti–PDL-1 inhibitors

    • Atezolizumab

    • Durvalumab

    • Avelumab

  • FDA-approved anti-PD1 inhibitors

    • Nivolumab

    • Pembrolizumab

  • All are approved for second-line treatment of locally advanced or metastatic urothelial cancer that progressed during or after platinum-based chemotherapy

  • Additionally, atezolizumab and pembrolizumab are approved as first-line therapy in

    • Cisplatin-ineligible patients whose tumors express PD-L1 or

    • Patients ineligible for any platinum-based chemotherapy regardless of PD-L1 expression 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 a urologist

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

• Metastatic urothelial cancer should be managed by a medical oncologist