1757 CYTOKERATIN 18 AND EAU SCORE PREDICT TUMOR RECURRENCE IN PATIENTS WITH NON-MUSCLE-INVASIVE BLADDER CANCER FOLLOWING SINGLE POSTOPERATIVE IMMEDIATE INTRAVESICAL CHEMOTHERAPY INSTILLATION

Abstract

INTRODUCTION AND OBJECTIVES: According to the European Association of Urology (EAU) guidelines, intravesical chemotherapy should be performed immediately after transurethral resection of the bladder tumor (TURBT) in all patients with non-muscle invasive bladder cancer (NMIBC). We examined the prognostic factors for recurrence after TURBT using molecular markers as well as the scoring system of the EAU. METHODS: Eighty-eight patients with primary or recurrent bladder tumors who underwent TURBT, followed by the single postoperative immediate instillation of pirarubicin (30 mg) and no further instillations of chemotherapy or BCG were enrolled between 2003 and 2006; the median follow-up period was 46 months. The time to first recurrence was the primary endpoint of this study. Patients were divided into 3 EAU recurrence risk groups as follows: low-risk group (total score, 0), intermediate-risk group (score, 1–9) and high-risk group (score, 9–17). The intermediate-risk group patients were subdivided into score of 1–4 and score of 5–9. Immunostaining using Ki-67, pHH3 (phospho-Histone H3; mitotic marker), CK18 (cytokeratin 18) and Survivin (cytoplasmic staining and nuclear staining) were performed on the TURBT specimens. RESULTS: According to the EAU risk stratification, 5, 82, and 1 were assigned to the low, intermediate and high-risk recurrence groups, respectively. During the follow-up period, recurrences were observed in 0% of the low-risk group, 45% (37 out of 82) in the intermediate-risk group, and 100% in the high-risk group. We evaluated various predictors of a recurrence-free outcome among the 82 intermediate-risk patients. In univariate analyses, EAU score stratification (1–4, 32.1% vs. 5–9, 62.1%), high CK18 expression (nega, 31.4% vs. posi, 88.8%), a high Ki-67 labeling index ( 5%, 35.4% vs. 5%, 52.5%) and high Survivin nuclear staining ( 5%, 35.9% vs. 5%, 62.5%) were significantly associated with recurrence. In a multivariate analysis, EAU score stratification (HR 2.95, p 0.003) and a higher expression of CK18 immunostaining (HR 6.70, p 0.0001) were independent predictors of disease recurrence. CONCLUSIONS: A single immediate chemotherapy instillation is, by itself, insufficient for the treatment of patients in the intermediate or high risk recurrence groups defined by the EAU guidelines. Strong immunohistochemical expression of CK18 and the EAU scoring system appeared to be independent predictors of clinical outcome among patients with urothelial carcinoma of the bladder.