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SWOG 8710 (INT-0080): Randomized Phase III Trial of Neoadjuvant MVAC+Cystectomy Versus Cystectomy Alone in Patients With Locally Advanced Bladder Cancer

James Metz, MD

University of Pennsylvania Cancer
Last Modified: May 14, 2001

Presenter: R.B. Natale
Affiliation: SWOG

Background:

Radical cystectomy has been the gold standard for the treatment of locally advanced bladder cancer. However, 50-60% develop recurrent or metastatic disease after cystectomy. It has been hypothesized that neoadjuvant therapy for advanced bladder cancer will 1)immediately treat micrometastatic disease, 2) downstage tumors and improve efficacy of surgery, and 3)allow better tolerance and compliance to chemotherapy when compared to adjuvant chemotherapy. This trial was designed to test MVAC in the neoadjuvant setting.

Materials and Methods:

• 317 patients with T2-4N0M0 transitional cell carcinoma of the bladder were enrolled over a period of 12 years
• Patients were randomized to cystectomy alone (arm 1) vs 3 cycles of MVAC prior to cystectomy (arm 2)

Results:

• Arm 2 had a 33% incidence of grade IV granulocytopenia and 29% incidence of GI complications
• 82% underwent the planned cystectomy in each arm
• There was no difference in the post-cystectomy complication rates
• 5 yr overall survival was 57% vs 42% favoring the MVAC arm (p<0.044, 1 sided t-test)
• Patients with a pathologic complete response had an overall survival of 85% at 5 years

Authors' Conclusions

• MVAC is safe prior to radical cystectomy, although toxicity can be moderately severe
• MVAC does not decrease the chances of a patient having a radical cystectomy
• This is the first randomized trial to show both a clinically and statistically significant advantage to the addition of neoadjuvant chemotherapy in locally advanced bladder cancer
• Neoadjuvant MVAC can be offered as a treatment option
• A confirmatory trial is needed to support these results

Clinical/Scientific Implications:

This is a controversial trial for a number of reasons. It accrued patients over a long period of time(12 years) which questions the selection of patients for this trial and the broad applicability to patients. There is significant controversy regarding the choice of statistical analysis of using a one sided t-test. If a 2 sided t-test was used, this trial would not be statistically significant. Seven previous randomized trials of neoadjuvant chemotherapy for advanced bladder cancer have been negative. Although neoadjuvant therapy with MVAC is an option, it should not be considered the standard of care until a confirmatory trial is performed.