| Abstract: |
In this prospective biomarker study, we evaluated the prognostic significance of Ki67, p53 and angiogenesis in patients with locally advanced bladder cancer. The patients were volunteers from a Southwest Oncology Group trial of locally advanced bladder cancer who were randomized to treatment with neoadjuvant chemotherapy plus cystectomy or cystectomy alone. Tissue specimens were obtained prior to neoadjuvant chemotherapy from 42 patients randomized to receive the combination-treatment arm and 52 randomized to cystectomy alone. The statistical power of the study was quite limited by the small sample size. The biomarkers were assayed by immunohistochemistry. Angiogenesis was determined using anti-CD34 immunostaining. Patients whose tumors had increased Ki67 expression had better progress ion-free survival that was marginally significant, p=0.063. The median survival in those with higher Ki67 expression was 73 months, and in those with lower expression was 38 months. However, this did not achieve statistical significance, p=0.25. There was a suggestion of worse survival among patients whose tumors exhibited altered p53 staining [hazard ratio (HR)=1.48; p=0.15], but there was no difference in progression-free survival (HR=1.02; p=0.93). The enumeration of tumor microvessels did not provide prognostic information. with aggressive surgical extirpation, 56% of patients with pathologic stage T3 disease (invasion of perivesical tissue) have tumor recurrence, which occurs most commonly as distant metastases (1). In 1987, the Southwest Oncology Group (SWOG) initiated a study to determine if neoadjuvant chemotherapy would improve the outcome for patients with locally advanced bladder cancer. Patients were randomized to 3 cycles of M-VAC (methotrexate, vinblastine, doxorubicin and cisplatin) and cystectomy or cystectomy alone. In 1994, the NCI Bladder Cancer Marker Network and SWOG initiated a companion trial to study three promising indicators of prognosis. The clinical trial has been published and demonstrated that patients receiving neoadjuvant chemotherapy and radical cystectomy lived 2.6 years longer than patients treated with cystectomy alone (2). The results of the companion biomarker study evaluating Ki67, p53 and angiogenesis in these patients are now being reported. |
