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

Study Type – Prognosis (case series) Level of Evidence 4 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.