Improved cancer specific-survival in patients with carcinoma invading bladder muscle expressing cyclo-oxygenase-2

OBJECTIVE To determine whether the expression of cyclo-oxygenase (COX)-2 has an influence on survival and on the response to chemotherapy in invasive bladder cancer. PATIENTS AND METHODS A population of 266 patients from a tertiary university centre with carcinoma invading bladder muscle without evidence of metastasis at time of cystectomy was analyzed retrospectively. COX-2 expression was evaluated immunohistochemically with a monoclonal anti-COX-2 antibody. All pertinent clinical and pathological parameters were reviewed and correlated with risk factors influencing outcome, including disease-specific and overall survival, as well as COX-2 expression. Immunoreactivity was categorized as positive if COX-2 staining was present in > 5% tumour cells. RESULTS The expression of COX-2 was not influenced by tumour stage, grade or nodal status, nor any other parameters. The risk factors that influenced disease-specific survival in carcinoma invading bladder muscle on multivariate analysis were lymph node status (hazards ratio, HR = 2.46 for N1, P = 0.001, HR = 2.90 for N2, P < 0.001, HR = 5.19 for N3, P = 0.012), use of neoadjuvant chemotherapy (HR = 3.54; P = 0.004) or adjuvant chemotherapy (HR = 0.57, P = 0.014) and COX-2 expression (HR = 0.64 if > 5% cells had positive expression; P = 0.025). Kaplan-Meier analysis showed an increased disease-specific survival (P = 0.0063), as well as longer recurrence-free survival (P = 0.003), in patients with muscle-invasive bladder tumours expressing COX-2 in > 5% of the cells. A tendency was also observed in a subgroup with positive nodes treated with adjuvant chemotherapy (P = 0.093). CONCLUSIONS The overexpression of COX-2 is associated with a better recurrence-free and disease-specific survival in a large cohort of 266 patients with carcinoma invading bladder muscle treated by cystectomy. A trend for increased disease-specific survival was also observed for patients with COX-2 overexpression and positive nodes who received adjuvant chemotherapy. Potential of COX-2 as a prognostic marker in bladder cancer should be considered.