Localized and locally advanced bladder cancer.

Localized and locally advanced bladder cancer represents a heterogeneous spectrum of diseases with different biologic and clinical behavior. It varies with respect to invasive potential, propensity for metastases, and sensitivity to chemotherapy. Although several significant surgical advances have been made over the past 20 years in the treatment of muscle-invasive bladder cancer, resulting in decreases in perioperative morbidity and mortality and improvement of quality of life in patients with continent urinary diversions, the natural history of the disease has remained unaltered. Advances in chemotherapy for metastatic disease have prompted trials of systemic therapy in patients with early stage, high-risk disease administered before or after local therapy consisting of cystectomy or radiotherapy. The data available from nonrandomized and randomized trials have not definitively established the exact role of neoadjuvant chemotherapy and its impact on survival. Even if neoadjuvant chemotherapy does not improve survival, preliminary data suggest that bladder preservation may be possible in selected patients and that such combined therapy will hopefully lead to better patient management. The trials of postoperative chemotherapy provide insufficient evidence to support the routine use of adjuvant chemotherapy in clinical practice as a result of small sample size, confusing analyses, and the reporting of questionable conclusions. New large-scale, multicenter trials are imperative to provide convincing results. A better understanding of the microbiology of bladder cancer will influence the search for new therapeutic modalities. Molecular-targeted small-molecule therapy and monoclonal antibodies have begun to dominate contemporary studies.