This study summarizes a landmark study on the role of neoadjuvant chemotherapy with methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC) in patients with muscle-invasive bladder cancer. This randomized study of M-VAC plus cystectomy versus cystectomy alone suggested improved overall survival in patients receiving neoadjuvant therapy. Severe granulocytopenia was a common adverse effect in the chemotherapy group, but no deaths were attributed to chemotherapy.