Optimal therapy for locally advanced bladder cancer ups survival

August 1, 2005

Orlando, FL--Radical cystectomy with pelvic lymph node dissection is the mainstay surgical treatment of locally advanced bladder cancer. Despite aggressive surgery, half of patients experience recurrence and die of the disease following cystectomy alone. However, there is evidence that patients receiving optimizing therapy (ie, neoadjuvant chemotherapy before cystectomy, radical cystectomy, and adequate lymph node dissection) have prolonged survival, compared with those treated with cystectomy only.

That was the conclusion of Memorial Sloan-Kettering Cancer Center researchers in a retrospective analysis of the data from a Southwest Oncology Group study.

"Patients with locally advanced bladder cancer have significantly improved freedom from local recurrence and [better] survival when therapy is optimized to include neoadjuvant chemotherapy, cystectomy, and adequate lymphadenectomy. Patients who failed to undergo radical cystectomy had a dismal prognosis," said Zohar A. Dotan, MD, PhD, a urologic oncology fellow at Memorial Sloan-Kettering working with Harry W. Herr, MD, and colleagues.

Over an 11-year period (1987 to 1998), the complete records of 307 of the original 317 patients (97%) became available for review. Of those, 39 (13%) did not have a cystectomy for reasons such as aborted surgery or patient refusal to consent to the procedure. The median follow-up time for the 307 patients was 8.4 years.

"We classified the patients according to the status of chemotherapy, cystectomy, surgical margin following cystectomy, and the number of pelvic lymph nodes removed according to the pathology report. We observed that patients who had cystectomy with negative surgical margins and removal of 10 lymph nodes following chemotherapy had the best outcome (freedom from local recurrence of 91% and overall survival of 81% at 5 years). Patients who had suboptimal therapy had decreased probability of freedom from local recurrence and shorter overall survival," Dr. Dotan told Urology Times at the American Society of Clinical Oncology annual meeting.

Although the study clearly showed that the combination therapy was associated with prolonged overall survival of patients with locally advanced bladder cancer, "there are debatable questions regarding the timing of chemotherapy (prior or after surgical therapy), the extension of lymph node dissection, and the definition of optimal therapy for locally advanced bladder cancer," he said.

Dr. Dotan defines optimized surgery as removal of the bladder, radical cystectomy with wide resection, and wide resection of the lymph nodes and soft tissue around the bladder. The main limitations are the retrospective nature of the analysis and the fact that the patients were not randomized for the different surgical variables such as the extent of the perivesical and lymph node dissections.

"The standard of care in the United States for locally advanced bladder cancer is radical cystectomy. Neoadjuvant chemotherapy prior to cystectomy for those patients is becoming more popular due to the promising data from the original SWOG 8710 trial. We hope that our observation of improving the outcome of those patients following neoadjuvant chemotherapy and optimal surgery will be validated by our studies," Dr. Dotan explained.