Elsevier

The Lancet

Volume 374, Issue 9685, 18–24 July 2009, Pages 239-249
The Lancet

Seminar
Bladder cancer

https://doi.org/10.1016/S0140-6736(09)60491-8Get rights and content

Summary

Bladder cancer is a heterogeneous disease, with 70% of patients presenting with superficial tumours, which tend to recur but are generally not life threatening, and 30% presenting as muscle-invasive disease associated with a high risk of death from distant metastases. The main presenting symptom of all bladder cancers is painless haematuria, and the diagnosis is established by urinary cytology and transurethral tumour resection. Intravesical treatment is used for carcinoma in situ and other high grade non-muscle-invasive tumours. The standard of care for muscle-invasive disease is radical cystoprostatectomy, and several types of urinary diversions are offered to patients, with quality of life as an important consideration. Bladder preservation with transurethral tumour resection, rad iation, and chemotherapy can in some cases be equally curative. Several chemotherapeutic agents have proven to be useful as neoadjuvant or adjuvant treatment and in patients with metastatic disease. We discuss bladder preserving approaches, combination chemotherapy including new agents, targeted therapies, and advances in molecular biology.

Section snippets

Epidemiology

Bladder cancer is the second most common genitourinary malignant disease in the USA, with an expected 69 000 newly diagnosed cases in 2008, and 14 000 deaths. The incidence of bladder cancer rises with age, peaking between age 50 years and 70 years, and is three times more common in men than in women.1 Risk factors for the development of bladder cancer can be classified into three subsets; genetic and molecular abnormalities, chemical or environmental exposures, and chronic irritation. Genetic

Pathophysiology and diagnosis

More than 90% of bladder cancers are transitional cell carcinomas, 5% are squamous cell carcinomas, and less than 2% are adenocarcinomas. The histopathological grading of transitional cell carcinoma of the bladder has historically been grade 1–3 as per the 1973 WHO classification system,17 but in 1998 a WHO and International Society of Urological Pathology consensus classified urothelial tumours into four categories; papilloma, papillary urothelial neoplasm of low malignant potential, low grade

Superficial bladder cancer

The high rate of recurrence is the feature of bladder cancer that makes follow-up a crucial component in effective management. After transurethral resection of the tumour, patients should have cystoscopy and voided urine cytology every 3 months for 2 years, then 6 monthly for 2 years, and then once yearly indefinitely. Upper tract imaging should be done every 12–24 months to establish whether a transitional cell carcinoma is present in the renal collecting system or ureters, because lifetime

Molecular biology and targeted therapies

Variations in chromosomal alterations arise at several points along the pathogenesis of transitional cell carcinoma. The loss of 9q seems to happen early in tumour development120 whereas the loss of 17p, 3p, 13q, 18q, and 10q is noted more frequently in high than in low grade and stage disease.121 When the range of genetic alterations in the pathogenesis of transitional cell carcinoma is compared, gains and amplifications are more frequent in advanced than in early stage disease, whereas

Search strategy and selection criteria

We searched Medline (1996–2008) and PubMed (1993–98), ClinicalTrials.gov, UpToDate database, and the National Cancer Institute Surveillance, Epidemiology and End Results Cancer Statistics Review 1975–2005. We used the search terms “bladder cancer”, “chemotherapy, bladder cancer”, “radiation therapy, bladder cancer”, “bladder presentation, cancer”, “invasive bladder cancer”, “neoadjuvant chemotherapy, bladder cancer”, “adjuvant chemotherapy, bladder cancer”, “chemotherapy, advanced bladder

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