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Bladder Cancer

Table of Contents
1 Disease Overview
        1.1 Risk Factors and Prevention
        1.2 Pathology
2 Diagnosis
3 Staging
4 Management of Bladder Cancer
        4.1 Noninvasive Bladder Cancer
        4.2 Invasive Bladder Cancer
        4.3 Perioperative Chemotherapy
        4.4 Metastatic Bladder Cancer

Disease Overview

    Bladder cancer is more common in men than women (1:4) and median age at diagnosis is 73. Approximately 8,000 (6,000 men and 2,000 women) new cases of bladder cancer and 2,200 (1,550 men and 640 women) related deaths were estimated to occur in Canada.

Risk Factors and Prevention

    Risk factors for bladder cancer include tobacco use, occupational exposures, urinary tract diseases, and pharmaceutical drug use. Cigarette smoking is strongly associated with an increased risk of bladder cancer among men and women. Occupational exposure to aromatic amines (particularly 2-naphthylamine, benzidine, and polycyclic aromatic hydrocarbons) is associated with an increased incidence of bladder cancer (e.g., workers in dyestuff manufacturing and rubber and aluminum industries). Infection with the trematode schistosoma haematobium leads to chronic irritation of the urothelium and to an increased risk of both squamous and urothelial carcinomas. Other chronic urinary tract infections, including stones and cystitis, also may lead to chronic inflammation and to an increased risk of bladder cancer. Heavy use of phenacetin-containing analgesics is associated with tumours of the renal pelvis and ureter, and cyclophosphamide also has been associated with an increased risk of urothelial carcinoma. These myriad risk factors lead to field changes within the urothelium that predispose individuals to the development of recurrent tumours, as well as to the involvement of new locations in the urothelial tract (polychronotropism).

Pathology

    Urothelial carcinoma may occur throughout the urinary tract (i.e., in any structure lined by the urothelium), with more than 90% of tumours originating in the bladder. Upper urinary tract tumours, including the renal pelvis and ureter, account for 5% to 7% of urothelial carcinomas, with renal pelvis tumours comprising the majority. In the United States, 92% of lower urinary tract tumours are urothelial carcinomas, 5% are squamous cell cancers, 2% are adenocarcinomas, and 1% are small cell carcinomas. Lesions of mixed histology generally are variants of urothelial carcinoma. Adenocarcinomas may be of urachal origin, occurring at the junction of the urachal ligament and bladder dome. In Northern Africa and other parts of the world where there is a high prevalence of infection with schistosoma haematobium, up to 75% of tumours are pure squamous cell carcinomas.

Diagnosis

    The most common presenting symptom is hematuria, and patients with carcinoma in situ or invasive disease may present with irritative urinary symptoms. Less frequently, patients present with symptoms related to distant metastases. The diagnosis is established by cystoscopy and biopsy.

Staging

The major problem with staging is that the correlation of depth of invasion determined by cystoscopy and biopsy with the results of cystectomy is only 50% to 60%. Non invasive imaging with CT or MRI can identify extravesical or nodal disease and is more reliable if done prior to the transurethral resection with a distended bladder. The histologic grading system of well differentiated (G1), moderately differentiated (G2), and poorly differentiated (G3) is more relevant for superficial tumours, because virtually all invasive neoplasms are poorly differentiated (G3).

Management of Bladder Cancer

Noninvasive Bladder Cancer

    Seventy percent of patients with newly diagnosed bladder cancer will present with noninvasive disease, with 70% confined to the mucosa (Ta or Tis) and 30% involving the submucosa (T1). The treatment involves complete removal of the lesion by transurethral resection followed by rigorous surveillance with cystoscopy and urine cytology at 3-month intervals for recurrence and/or progression to a more advanced stage. These cases are managed by the urologist.

Invasive Bladder Cancer

    Although the majority of patients present with noninvasive disease, approximately 20% to 40% of patients either present with more advanced disease or experience disease progression after therapy for noninvasive disease. Staging for patients with invasive disease includes a CT scan of the abdomen and pelvis, chest x-ray, and, if clinically indicated, a bone scan.

    The standard treatment for a muscle-invasive tumour is a radical cystectomy with bilateral pelvic lymphadenectomy that includes removal of the bladder, prostate, seminal vesicles, and proximal urethra for men, and removal of the bladder, urethra, and uterus (including bilateral salpingo-oophorectomy), as well as excision of a portion of the anterior vaginal wall, for women.

Perioperative Chemotherapy for Invasive and Locally Advanced Bladder Cancer

    The use of perioperative chemotherapy in the management of invasive and locally advanced bladder cancer has been studied in the neoadjuvant (preoperative) and adjuvant (postoperative) settings. The potential advantages for neoadjuvant chemotherapy include: evaluation of response to therapy in vivo with continuation of effective chemotherapy; discontinuation of chemotherapy and early cystectomy in the setting of no response or progression; tumour down staging to allow for a less complicated surgery; and the delivery of full-dose chemotherapy without the problems associated with postoperative recovery. The major advantages for the use of adjuvant chemotherapy include treatment based on pathologic criteria, with the ability to select those patients at high risk who are most likely to benefit from chemotherapy and to avoid the unnecessary treatment of patients with low-risk disease.

Metastatic Bladder Cancer

    Urothelial tumours are sensitive to several chemotherapy agents with different mechanisms of action, including methotrexate, vinblastine, doxorubicin, cisplatin, the taxanes, ifosfamide, pemetrexed, and gemcitabine. Two-, three-, and four-drug combinations have been used with the combination of methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) and gemcitabine plus cisplatin (GC) representing the standard regimens. Exciting research in bladder cancer regarding molecular types, targeted therapy and immunotherapy is ongoing and patients should be referred for testing for any mutations for the COMPACT trial at PMH.