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Chemotherapy Improves Survival In Bladder Cancer Patients Undergoing Radical Cystectomy

Among patients with locally advanced bladder cancer undergoing radical cystectomy, addition of neoadjuvant methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC) appears to increase the elimination of residual cancer and may improve survival.

Recurrence rate is significant after radical cystectomy for locally advanced bladder cancer and has been estimated at 56 percent among patients with pathological stage T3, in which there is invasion of perivesical tissue, according to H. Barton Grossman, MD, M.D. Anderson Cancer Center, Houston, Texas, United States, and colleagues.

The researchers conducted a study to evaluate the ability of neoadjuvant chemotherapy to improve the outcome in 307 patients with locally advanced bladder cancer who were treated with radical cystectomy.

Patients with muscle-invasive bladder cancer (stage T2 to T4a) scheduled to undergo radical cystectomy were stratified according to age (less than 65 years versus 65 years or older) and stage (superficial muscle invasion versus more extensive disease). The researchers randomly assigned 154 patients to radical cystectomy alone and 153 to 3 cycles of M-VAC before undergoing radical cystectomy.

An intention-to-treat analysis found that median survival among patients assigned to surgery alone was 46 months compared with 77 months among patients assigned to combination therapy (P=.06).

Improved survival was associated with the absence of residual cancer in the cystectomy specimen in both groups. However, 38% of the combination-therapy group had no residual disease compared to only 15% of patients in the cystectomy group (P<.001).

"Our study demonstrates that the four-drug combination M-VAC can be given safely before radical cystectomy to patients with locally advanced bladder cancer," the researchers conclude.

Adverse effects were moderate, all patients recovered, and no treatment-related deaths occurred, according to the researchers.

"Furthermore, M-VAC did not adversely affect a patient's chance of undergoing radical cystectomy, nor did it increase the risk of death or complications related to the surgery," they add.

Neoadjuvant M-VAC can be offered to patients with locally advanced bladder cancer who are candidates for radical cystectomy, they conclude. But they note that a safe and successful outcome with M-VAC "requires the selection of patients with adequate renal function, careful monitoring for chemotherapy-induced toxic effects, and appropriate intervention in the event of severe adverse effects."
N Engl J Med 2003;349:9:859-866. "Neoadjuvant chemotherapy plus cystectomy compared with cystectomy alone for locally advanced bladder cancer"

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