Chemotherapy in Locally Advanced and Metastatic Bladder Cancer

Abstract

The gold standard for the treatment of metastatic urothelial cancer over the past 15 years was a regimen including MVAC (methotrexate, vinblastine, adriamycin and cisplatin). It was demonstrated that this systemic approach revealed a significantly higher clinical efficacy when compared with different forms of combination chemotherapy, resulting in promising response and complete remission rates of up to 50% and 25%, respectively. Although it became evident that mainly patients with complete remissions reveal a favourable clinical prognosis, this advantage regarding overall survival becomes undetectable after 5 years of follow-up. Given that 25% of patients experience a complete tumor remission that persists for more than 3 years in about 50% of cases, a long lasting therapy-induced clinical benefit can be expected in only about 13% of patients. Therefore, the median long-term survival of patients with metastatic bladder cancer is roughly one year. Due to the observation that locally advanced tumors reveal a higher risk for the development of regional lymph node metastases already present at the time of surgery and that up to 50% of patients develop systemic tumor progression even following an aggressive local treatment, it has been postulated that an early chemotherapeutical treatment, either as neoadjuvant or adjuvant therapy in addition to local radiation or radical cystectomy, might improve the clinical prognosis of the patients due to an eradication of low-volume metastatic deposits. The present review tries to elucidate the clinical benefit that has been suggested to result from the latter treatment option. In addition, the role of new cytotoxic drugs like gemcitabine and paclitaxel during the therapy of metastatic urothelial cancer even in patients with significant comorbidity like impaired renal function as well as the impact on the patients’ clinical prognosis that might be derived from molecular targeting is discussed.