Sections View Full Chapter Figures Tables Videos Full Chapter Figures Tables Videos Supplementary Content + Print Section ++ For further information, see CMDT Part 39-18: Bladder Cancer + Key Features Print Section ++ ++ 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 + Clinical Findings Print Section ++ ++ 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 Print Section ++ ++ 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 + Treatment Print Section ++ ++ 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) + Outcome Print Section ++ ++ 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 + References Print Section ++ + +Babjuk M et al. EAU guidelines on non-muscle-invasive urothelial carcinoma of the bladder: update 2016. Eur Urol. 2017 Mar;71(3):447–61. [PubMed: 27324428] + +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] + +Johnson DC et al. Surgical advances in bladder cancer: at what cost? Urol Clin North Am. 2015 May;42(2):235–52. [PubMed: 25882565] + +Kamat AM et al. Bladder cancer. Lancet. 2016 Dec 3;388(10061):2796–810. Erratum in: Lancet. 2016 Dec 3;388(10061):2742. [PubMed: 27345655] + +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] + +Lerner SP et al. Novel endoscopic diagnosis for bladder cancer. Cancer. 2015 Jan 15;121(2):169–78. [PubMed: 25132313] + +Lucca I et al. Novel biomarkers to predict response and prognosis in localized bladder cancer. Urol Clin North Am. 2015 May;42(2):225–33. [PubMed: 25882564] + +Tripathi A et al Immunotherapy for urothelial carcinoma: current evidence and future directions. Curr Urol Rep. 2018 Nov 7;19(12):109. [PubMed: 30406502]