Molecular determination of perivesical and lymph node metastasis after radical cystectomy for urothelial carcinoma of the bladder

Purpose: Current methods used to determine the pathological stage of the pr imary tumor and associated lymphatics after radical cystectomy are tedious, costly, and may lack the sensitivity afforded by molecular approaches such as reverse transcription-PCR (RT-PCR) for markers specific for urothelial tissue such as the uroplakin II (UPII) gene. Thus, we sought to evaluate an objective and sensitive molecular approach for the assessment of perivesic al extension and lymph node status after radical cystectomy, based on the d etection of UPII expression using RT-PCR and compare this assay to standard clinical and pathological examination, Experimental Design: From November 1999 to September 2000, 27 patients with clinical T-a-T3N0M0 urothelial bladder cancer underwent radical cystectomy , 19 (70%) of which also had pelvic lymphadenectomy. At the completion of c ystectomy, systematic biopsies of the external surface of the bladder speci men as well as from the largest palpable lymph node found at lymphadenectom y were obtained for molecular analysis, RT-PCR analysis for UPII mRNA was c arried out on these biopsy specimens, and results were compared with data o btained from conventional pathological examination. Results: Pathologically organ-confined tumors had a 42% (5 of 12) incidence of positive signals in the perivesical tissues and 17% (1 of 7) in the lym ph nodes, Corresponding percentages for pT(3a)N(0) and pT(3b)-T4N0 lesions were 67% (4 of 6)/25% (1 of 4) and 67% (4 of 6)/33% (2 of 6), respectively. Overall, pathologcally node-negative cancers had a perivesical positivity rate of 54% (13 of 24) and a lymph node positivity rate of 25% (4 of 16), A ll patients with pathologically positive nodes had positive UPII signals in the lymph node sample, Conclusions: This molecular assay aimed at assessing perivesical extension and lymph node status after radical cystectomy appears to identify patients that may harbor residual disease not appreciated by conventional histology , Larger studies with 5-7-year follow-up will be required to determine the prognostic significance of such molecular information.