Intensity of androgen and epidermal growth factor receptor immunoreactivity in samples of radical prostatectomy as prognostic indicator: correlation with clinical data of long-term observations.

PURPOSE: We analyzed the potential prognostic significance of the immunohistochemical expression of androgen and growth factor receptors determined in prostatectomy specimens of patients with prostate cancer. MATERIALS AND METHODS: A cohort of 211 patients with locally confined prostate cancer treated with radical prostatectomy with or without antiandrogen pretreatment between January 1, 1990 and August 31, 1996 was observed prospectively. Prostatectomy samples were processed immunohistochemically to visualize androgen and growth factor receptors, of which immunoreaction intensity was scored relative to that of positive control tissue. Clinical postoperative data were processed using the Kaplan-Meier method, log rank test, and univariate and multivariate explorative Cox modeling to evaluate the contribution to overall and relapse-free survival. RESULTS: There were statistical dependencies between the androgen receptor and epidermal growth factor receptor staining indexes. Following data stratification according to the epidermal growth factor receptor staining index the prognosis associated with a low androgen receptor staining index was worse than that with a higher androgen receptor staining index. Cox regression analysis for relapse-free survival confirmed that the risk factors low androgen receptor and increased epidermal growth factor receptor staining were associated with significantly increased relative risk. Univariate Kaplan-Meier analysis showed that patients with grade 3 carcinoma had a worse prognosis than those with better differentiated carcinoma, whereas antiandrogen pretreatment had no influence on overall survival or relapse-free survival. CONCLUSIONS: Using a multivariate proportional hazards regression model for data on a cohort of 211 patients with 68 showing relapse/progress or death from disease a low intensity of androgen receptor staining indicated a poor prognosis.

Adjuvant cisplatin plus methotrexate versus methotrexate, vinblastine, epirubicin, and cisplatin in locally advanced bladder cancer: results of a randomized, multicenter, phase III trial (AUO-AB 05/95).

PURPOSE: Radical cystectomy as standard treatment of muscle-invasive urothelial carcinoma of the urinary bladder cures less than 50% of patients with locally advanced bladder cancer. We compared two adjuvant combination chemotherapies in patients with stage pT3a-4a and/or pathologic node-positive transitional-cell carcinoma of the bladder after radical cystectomy. PATIENTS AND METHODS: A total of 327 patients were randomly assigned to either adjuvant systemic chemotherapy with three cycles of cisplatin 70 mg/qm(2) on day 1 and methotrexate 40 mg/qm(2) on days 8 and 15 of a 21-day cycle (CM) or three cycles of methotrexate 30 mg/qm(2) on days 1, 15, and 22, vinblastine 3 mg/qm(2) on days 2, 15, and 22, epirubicin 45 mg/qm(2) on day 2, and cisplatin 70 mg/qm(2) on day 2 of a 28-day cycle (M-VEC). RESULTS: The hazard ratio for progression-free survival as the primary end point was 1.13 (90% CI, 0.86 to 1.48) for 163 CM patients compared with 164 M-VEC patients whose right-hand limit remained below the upper bound compatible with the noninferiority hypothesis (alpha = .0403). The 5-year progression-free, tumor-specific, and overall survival rates (point estimates +/- SE) for CM versus M-VEC were 46.3% +/- 4.6% v 48.8% +/- 4.5%, 52.0% +/- 4.6% v 52.3% +/- 4.8%, and 46.1% +/- 4.3% v 45.1% +/- 4.6%, respectively. WHO grade 3 and 4 leukopenia occurred in 7.0% of patients treated with CM and 22.2% of patients treated with M-VEC (P < .0001). CONCLUSION: CM cannot be considered inferior to M-VEC with regard to progression-free survival of patients with locally advanced bladder cancer after radical cystectomy. Moreover, patients receiving adjuvant CM combination therapy experienced significantly less grade 3 and 4 leukopenia than patients treated with M-VEC.