Prognostic value of p53 nuclear overexpression in patients with invasive bladder cancer treated with neoadjuvant MVAC.

PURPOSE: This study sought to examine the prognostic role of p53 nuclear overexpression in muscle-invasive bladder cancer because of its correlation with progression of superficial bladder cancer. PATIENTS AND METHODS: Ninety of 111 patients treated with neoadjuvant methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) with a median follow-up duration of 5.8 years were evaluated. p53 nuclear overexpression was determined by immunohistochemistry on deparaffinized tissue sections. Patients were stratified into two groups according to the percent of tumor cells with positive nuclear reactivity. Overexpression was defined as tumors with > or = 20% cells with positive nuclear reactivity and nonoverexpression as tumors with less than 20% reactivity. RESULTS: Nuclear overexpression was observed in 47 patients and nonoverexpression in 43 patients. Patients whose tumors had p53 overexpression had a significantly higher proportion of cancer deaths. A multivariate analysis that evaluated the pretreatment variables p53 nuclear overexpression, age, sex, palpable mass, prechemotherapy tumor stage, performance status, ureteral obstruction, tumor size, multifocality, and grade showed that p53 overexpression had independent significance for survival (P = .001; relative risk ratio, 3.1). The impact of p53 overexpression on survival was predominantly in T2 and T3a tumors. Long-term survival was evident in seven of 17 patients (41%) with p53 overexpression versus 20 of 26 (77%) in whom p53 was not overexpressed (P = .007). CONCLUSION: p53 nuclear overexpression has independent prognostic value for survival in patients with invasive bladder cancer treated with neoadjuvant chemotherapy.

Post-therapy change in prostate-specific antigen levels as a clinical trial endpoint in hormone-refractory prostatic cancer: a trial with 10-ethyl-deaza-aminopterin.

OBJECTIVES: Serial changes in prostate-specific antigen (PSA) correlate with disease status in all stages of prostatic cancer. For hormone-refractory disease, post-therapy declines of 50% and 80% from baseline are associated with an improved survival. This study sought to evaluate edatrexate, a synthetic antifolate, in hormone-refractory prostatic cancer using post-therapy PSA change as the initial endpoint. METHODS: Fourteen patients with progression of disease despite castrate levels of testosterone received edatrexate. Serial changes in PSA were monitored and correlated with other parameters of outcome. RESULTS: Stabilization of a rising PSA level in parallel with clinical stabilization of disease was observed in one patient; disease in all others progressed. Toxic reactions were acceptable. CONCLUSIONS: With no objective evidence for antitumor activity as assessed by post-therapy PSA changes in any of the patients treated, edatrexate seems a poor candidate for future study. The use of post-therapy PSA change as the initial screening modality allows treatments to be evaluated rapidly in patients without measurable disease. The methodology proposed will require validation in prospective phase III investigations using survival as the endpoint.

Neoadjuvant chemotherapy for invasive bladder cancer: prognostic factors for survival of patients treated with M-VAC with 5-year follow-up.

PURPOSE: To determine survival in patients with muscle-invasive bladder cancer treated with neoadjuvant chemotherapy and to analyze prechemotherapy and postchemotherapy factors for prognostic significance. PATIENTS AND METHODS: The survival of 111 patients with T2-4N0M0 bladder cancer treated with neoadjuvant methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC) was assessed. Prechemotherapy and postchemotherapy factors were analyzed for correlation with survival. Factors found to be significant on univariate analysis were subjected to multivariate analysis using Cox's proportional hazards model. RESULTS: The median follow-up duration was 5.3 years. Initial tumor (T) stage (P = .0001), presence of ureteral obstruction (P = .0074), and presence of a palpable mass (P = .0039) were the only pretreatment factors found to be significant on univariate analysis. Postchemotherapy surgery was performed in 81 patients. In these cases, postchemotherapy clinical stage and pathologic stage were significant factors on univariate analysis. In the multivariate analysis, the initial prechemotherapy T stage and the postchemotherapy pathologic stage (pT stage) were the only two factors to demonstrate independent significance. An association between downstaging postchemotherapy and survival was observed for patients with extravesical disease (T < or = 3B) at the start of treatment. In this subset, the 5-year survival rate was 54% for patients with downstaging versus 12% for those without downstaging. This association was not observed for patients with bladder-confined disease (T < or = 3A) at presentation. CONCLUSION: The stage of bladder cancer at presentation and at postchemotherapy pathologic staging are independent prognostic factors for long-term survival in patients treated with neoadjuvant chemotherapy. Downstaging after neoadjuvant chemotherapy was associated with improved survival in patients with muscle-invasive bladder cancers, but only for those with extravesical disease (T > or = 3B) pretreatment. Randomized comparisons will be required to assess the impact of chemotherapy on overall survival.