Study On The Prognosis Of Upper Urinary Tract Transitional Cell Carcinoma

Objective: To identify variables that were predictive of progression-free (PFS) and bladder tumor-free survival rate (RFS) in patients with Transitional Cell Carcinoma of the Upper Urinary Tract (UUT-TCC). The related clinical and pathologic factors as well as tumor markers that may affect prognosis of the urothelium carcinoma were screened by univariate and multivariate analysis. Set up a prognostic model which may stratify the patients into different risk groups as a tool for prognosis prediction to UUT-TCC.Methods:1. Clinical and pathologic data from 219 patients who underwent nephroureterectomy (NU) for UUT-TCC from 1997 to 2006 in The Second Hospital of Tianjin Medical University were collected retrospectively. Among these patients, only 168 were included because they were followed up and in accordance with the inclusive criteria, and their paraffin-embedded specimens were available for detecting the expression of P53, Ki-67, E-cadherin, FGFR-3 and MVD by immunohistochemistry.2. In univariate analysis, Kaplan-Meier survival curves were generated and compared by Log-rank test. The following factors were included in the analysis: age, sex, macroscopic hematuria, tumor location, sides, operating types for distal ureter, bladder instillation, numbers and sites of tumors, pathologic grade, TNM classification, bladder tumor recurrence and the expression of P53, Ki-67, E-cadherin, FGFR-3 and MVD.3. All significant factors in the univariate analysis or to be considered necessary for the study entered into multivariate analysis. A stepwise, forward-selection strategy was used to screen factors and set the Cox PH models for PFS and RFS. The Proportional Hazards assumption of the Cox model was evaluated by Harrel's test and a graphical procedure.4. Evaluating the model's accuracy for predicting to the prognosis by comparing the difference with the TNM classification and between the three risk groups.Results:1. The 1-year, 3-year, and 5-year PFS and USS of these patients were 96%, 75%, 71% and 88%, 72%, 68% respectively, and the RFS at 1, 3 and 5 years were 88%, 76% and 63%. 2. The ratio of patients with positive expression of P53, Ki-67, FGFR-3 and abnormal expression of E-cadherin were 64.3%, 40.5%, 49.4% and 44.0% respectively. MVD were higher than the median value in 47.6% patients. The expression of E-cadherin, FGFR-3 and MVD were correlated with TNM classification, and the expression of P53, Ki-67, FGFR-3, E-cadherin, MVD were correlated with tumor grades.3. Significant factors for progression on univariate analysis were: tumor size, bladder instillation, tumor grades, tumor stage, expression of P53, Ki-67, E-cadherin, FGFR-3 and MVD. Tumor grade, bladder insillation, tumor numbers, expression of Ki-67 and proximal ureter were associated with bladder recurrence probabilities. Bladder tumors developed in 67.3% of recurrent patients during the first 2 years after NU and tended to locate on the same sides of previous UUT-TCC, especially around the orifice of ureters. The grade of recurrent bladder tumors were correlated with the grade of previous UUT-TCC.4. On multivariate analysis, tumor grade, stage, expression of P53 and E-cadherin were associated with PFS and USS; Tumor grade, bladder instillation, tumor numbers and proximal ureter were independent risk factors for bladder recurrence.5. In the progression risk model, the progression probabilities at 1, 3 and 5 years after NU were 0%, 2%, 5% for low risk group; 10%, 24%, 29% for middle risk group and 29%, 76%, 80% for high risk group. In the bladder recurrence risk model, the 1-year, 3-year and 5-year recurrence probabilities were 6%, 9%, 20% for low risk group; 13%, 27%, 45% for middle risk group and 31%, 47%, 75% for high risk group.Conclusion:1. Grade and stage of tumors, expression of P53 and E-cadherin were independent factors associated with PFS and USS.2. Tumor grades, bladder instillation, tumor numbers and proximal ureter tumor were independent factors for RFS, but none of the tumor markers detected in this study were associated with such a hazard.3. Most recurrent bladder tumors developed during the first 2 years after NU, and tended to locate around the orifice on the same sides of previous UUT-TCC. Bladder recurrence did not affect the USS and PFS.4. Intravesical instillation can reduce the risk of bladder recurrent tumors after NU.5. By stratifying patients with all independent risk factors, the prognostic score model developed in this study may improve the accuracy for prognosis prediction to patients with UUT-TCC.