No Clear Role for Neoadjuvant Chemotherapy in Bladder Cancer

CHICAGO—Systemic chemotherapy would seem to be a reasonable option to reduce the number of deaths from metastatic transitional cell bladder carcinoma. To date, however, systemic neoadjuvant chemotherapy has failed to show an effect on survival, and the jury is still out on the issue of chemotherapy following definitive therapy, said Derek Raghavan, MD, chief of medical oncology, University of Southern California Norris Cancer Center.

In the early 1980s, preliminary findings from trials of neoadjuvant chemotherapy in patients with high-grade T3 and T4 transitional cell carcinoma treated at the Royal Prince Alfred Hospital, Sydney, Australia, suggested that two cycles of cisplatin before definitive therapy might increase survival.

Follow-up randomized trials have not confirmed that neoadjuvant chemotherapy confers a survival benefit, however, Dr. Raghavan said at the Chicago Prostate Cancer Shootout III Plus Bladder Conference, sponsored by the Chicago Urological Society, Chicago Radiological Society, and Chicago Medical Society.

Early reporting from one of the best- designed randomized trials conducted by EORTC in 1996 has shown no difference in survival when CMV (cisplatin, methotrexate, vinblastine) was given before definitive treatment for bladder cancer. The aim of the trial was to try to detect a 10% increase in 3-year survival among 975 bladder cancer patients treated in 16 countries, “which is not asking for too much,” Dr. Raghavan said.

Nevertheless, there was no difference in any of the survival measurements. Two-year disease-free survival was 51% in CMV-treated patients and 45% in controls; overall 2-year survival was 62% in CMV patients and 60% in controls.

These results are preliminary and, therefore, could change over time, he noted. However, since the findings “failed to show a survival benefit at first analysis, we have no basis for using neoadjuvant chemotherapy from this trial,” Dr. Raghavan commented. The RTOG trial of neoadjuvant CMV has provided “another nail in the coffin for neoadjuvant therapy,” Dr. Raghavan said, because there was no difference in actuarial 5-year survival (49% for CMV-treated patients vs 48% for nontreated patients) and no difference in overall 3-year survival.

Trials of adjuvant therapy after chemotherapy and surgery have indicated that there may be at least some effect on survival; however, many of these trials have been poorly designed, Dr. Raghavan said.

A study conducted by Freiha in 1996 demonstrated a trend toward increased survival with adjuvant CMV after cystectomy, but it closed early and therefore had too few cases to support the use of adjuvant treatment.

At present, therefore, Dr. Raghavan said, “there is no routine role for adjuvant chemotherapy other than in very carefully selected patients or in the context of clinical trials.”