Radical cystectomy is the current gold standard treatment for locally advanced bladder cancers. However, 50-60% of patients develop recurrent, metastatic disease due to occult micrometastases at the time of surgery.

Chemotherapy has been used prior to surgery in the treatment of cancers such as breast cancer to downstage the primary tumor and enable an early attack on micrometastases. To date, neoadjuvant chemotherapy for bladder cancer has not been considered standard treatment.

Dr. Ronald Natale presented results from a multi-group Phase III study designed to determine whether neoadjuvant therapy prolongs survival in patients with locally advanced bladder cancer. The results of the study raise debate about its role as a possible new standard therapy for the disease.

The study, which was conducted over 14 years, involved 317 patients with locally advanced transitional cell carcinoma of the bladder with no disease outside the bladder and no prior systemic chemotherapy. They were randomized to receive cystectomy alone or chemotherapy followed by cystectomy.

The chemotherapeutic combination of methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC), the current standard combination for treatment of metastatic bladder cancer, was used as neoadjuvant therapy in the study.

Toxicity associated with this chemotherapeutic regimen included Grade 4 granulocytopenia in 33% of patients and Grade 3/4 gastrointestinal toxicity in 29%. There were no differences in postoperative complications between the two groups.

Median survival for patients receiving neoadjuvant chemotherapy was 6.2 years compared with median survival of 3.8 years in patients receiving radical cystectomy alone. Five-year survival was 57% and 42% in the two groups, respectively.

At time of surgery, 38% of patients in the chemotherapy group were found to be pathologically free of cancer. These patients had an 85% five-year survival rate, accounting for most of the survival advantage in the neoadjuvant group.

Dr. Natale noted that although one successful clinical trial cannot change standard medical practice, results of the current study suggest that neoadjuvant combination chemotherapy should be considered a treatment option in locally advanced bladder cancer.