Sections View Full Chapter Figures Tables Videos Annotate Full Chapter Figures Tables Videos Supplementary Content + Download Section PDF Listen ++ For further information, see CMDT Part 39-18: Bladder Cancer + Key Features Download Section PDF Listen +++ +++ 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 + Clinical Findings Download Section PDF Listen +++ +++ 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 + Diagnosis Download Section PDF Listen +++ +++ 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 + Treatment Download Section PDF Listen +++ +++ 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 + Outcome Download Section PDF Listen +++ +++ 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 + References Download Section PDF Listen +++ + +Babjuk M et al. European Association of Urology guidelines on non-muscle-invasive bladder cancer (TaT1 and carcinoma in situ) – 2019 update. Eur Urol. 2019 Nov;76(5):639–57. [PubMed: 31443960] + +Bellmunt J et al; KEYNOTE-045 Investigators. Pembrolizumab as second-line therapy for advanced urothelial carcinoma. N Engl J Med. 2017 Mar 16;376(11):1015–26. [PubMed: 28212060] + +Faba OR et al. Update of the ICUD-SIU International Consultation on Bladder Cancer 2018: urinary diversion. World J Urol. 2019 Jan;37(1):85–93. [PubMed: 30238399] + +Hussain SA et al. From clinical trials to real-life clinical practice: the role of immunotherapy with PD-1/PD-L1 inhibitors in advanced urothelial carcinoma. Eur Urol Oncol. 2018 Dec;1(6):486–500. [PubMed: 31158093] + +Lee CH et al. Role of imaging in the local staging of urothelial carcinoma of the bladder. AJR Am J Roentgenol. 2017 Jun;208(6):1193–205. [PubMed: 28225635] + +Nadal R et al. Management of metastatic bladder cancer. Cancer Treat Rev. 2019 Jun;76:10–21. [PubMed: 31030123] + +Parekh DJ et al. Robot-assisted radical cystectomy versus open radical cystectomy in patients with bladder cancer (RAZOR): an open-label, randomised, phase 3, non-inferiority trial. Lancet. 2018 Jun 23;391(10139):2525–36. [PubMed: 29976469] + +Patel VG et al. Treatment of muscle-invasive and advanced bladder cancer in 2020. CA Cancer J Clin. 2020 Aug 7. [Epub ahead of print] [PubMed: 32767764]