Adjuvant chemotherapy for deep muscle-invasive transitional cell bladder carcinoma - a practice guideline.

BACKGROUND AND PURPOSE: To examine the role of adjuvant chemotherapy in the treatment of patients with deep muscle-invasive transitional cell carcinoma (TCC) of the bladder who have undergone cystectomy. MATERIALS AND METHODS: A systematic review of the published literature was combined with a consensus process, involving the interpretation of evidence within the context of conventional practice, to develop an evidence-based practice guideline for use in Ontario. RESULTS: Five randomized controlled trials (RCTs) comparing adjuvant chemotherapy with observation were found that reported data on survival. Sample sizes of the trials were small, and each of the trials evaluated a cisplatin-based chemotherapy regimen; however, none studied less toxic combination chemotherapy regimens such as gemcitabine-cisplatin or dose-intensive methotrexate-vinblastine-doxorubicin-cisplatin (MVAC) with granulocyte-colony stimulating factor (G-CSF). One trial was excluded due to inadequate reporting of outcomes. The remaining four studies failed to demonstrate an overall survival benefit in favor of adjuvant chemotherapy, although three of the four trials showed statistically significant benefits for adjuvant chemotherapy with respect to disease-free survival. CONCLUSIONS: As randomized trials have not proven a benefit in overall survival, adult patients with deep muscle-invasive TCC of the bladder should not be routinely offered adjuvant chemotherapy following cystectomy. Disease-free survival may be improved by adjuvant chemotherapy, but it is unclear whether this improvement compensates for the detrimental effects of chemotherapy. If a patient chooses adjuvant chemotherapy to improve disease-free survival they should be made aware of the lack of proven overall survival benefit, and a cisplatin-based combination chemotherapy regimen such as MVAC or CMV is recommended. RCTs of gemcitabine-cisplatin and dose-intensive MVAC plus G-CSF in the setting of metastatic TCC of the bladder provide indirect evidence that these regimens could offer equivalent benefit to MVAC and CMV but with less toxicity in patients with muscle-invasive disease. The use of these regimens in the adjuvant setting after cystectomy is currently being evaluated in a randomized trial (EORTC trial 30994).