| Section 1:Risk Factors of Intravesical Recurrence and Prognosis Outcomes after Radical Nephroureterectomy for Upper Tract Urothelial CarcinomasObjective To analysis the risk factors for the intravesical recurrence after radical nephroureterectom (RNU) for primary upper tract urothelial carcinomas (UTUC). And to explore the influence of intravesical recurrence as well as clinicopathologic factors on oncologic outcomes for UTUC.Methods 115 patients with primary UTUC after RNU were retrospectively collected between Mar 2004 and Feb 2014 in Beijing Hospital of the Ministry of Health. The expression of tumor markers Ki-67 and P53 protein was detected by immunohistochemistry. The relationship between Ki-67 and P53 expression and clinicopathological features was evaluated. Combined with cliniopathological factors and molecular markers, effective predictive markers for recurrence and prognosis were analyzed in patients with UTUC. The SPSS 16.0 was used for statistical analysis.Results1. Relationship between intravesical recurrence and oncologic outcomes The median follow-up time was 54.4 months (7 to 130 mo), and the incidence of intravesical recurrence was 11.3%(13/115) in patients with the primary UTUC after RNU. The mean progression free survival time (PFS) was 92.1±13.3 and 112.8±4.3 mo respectively in recurrence group and non-recurrence group. There was no significant difference between those two groups (P=0.491). The mean disease specific survival time (CSS) was 113.50±4.25 and 116.00±4.95 mo. There was no significant difference between those two groups (P> 0.05).2. Risk factors for intravesical recurrence and risk stratification for UTUC Multivariate survival analysis revealed that more than 65 years old (P=0.040). low ureteral cancer (P=0.008) and low level Ki-67 expression (P=0.041) were independent predictors for intravesical recurrence. According to risk factors, patients were stratified to low risk group, intermediate risk group and high risk group. Intravesical recurrence free time were 121.5±2.4 mo,114.7±8.4mo and 59.3±13.2 mo respectively (P<0.001) in those three groups.3. Predictive markers for prognosis in patients with UTUC Multivariate Cox regression analysis found that the positive cytology (P= 0.012), advanced stage (P= 0.004) and lymph node metastasis (P= 0.018) were independent risk factors for PFS. Advanced stage (P= 0.005). tumor pathological type (lymphovascular invasion and sarcomas, P= 0.015) and lymph node metastasis (P< 0.001) associated with CSS.Conclusion There was no relationship between intravesical recurrence and oncological outcomes. Advanced stage and lymph node metastasis were still important prognostic factors for UTUC. Older age. lower ureteral cancer and low level Ki-67 expression were independent predictors for intravesical recurrence in patients with primary UTUC after RNU. High risk patients for intravesical recurrence could be distinguished by risk stratification which could be used to individualize intravesical instillation.Section 2:A Clinical Study of Prophylactic Intravesical Chemotherapy Schedule in Patients with Upper Tract Urothelial Carcinoma after Radical Nephroureterectomy and a Meta-analysisObjective To assess the impact of single intravesical chemotherapy and repeated instillation on intravesical recurrence after radical nephroureterectomy(RNU) in upper tract urothelial carcinoma (UTUC).Methods 115 UTUC patients who underwent RNU were retrospectively collected between Mar 2004 and Feb 2014 in Beijing Hospital of the Ministry of Health. To compare the incidence rates of bladder cancer in instillation group and non-instillation group and different efficacy between single instillation and repeated instillation. A comprehensive literature search was performed in July 2014 using the Medline. Embase, and Cochrane Library, as well as Chinese journal literature databases. All clinical trials were included which were used to compare the effect of prophylactic intravesical chemotherapy after RNU for primary UTUC. Analysis was performed using the Stata 12.0 SE software. Fixed effect model (M-H) was used to pool odd ratio (OR) after heterogeneity test. The Begg and Egger analysis were used to evaluate the publication bias.Results1. Clinical study Bladder cancer incidence rates were 11.1%(3/27) and 11.4% (10/88) in instillation group and non-instillation group respectively. Intravesical recurrence rates were 18.2%(2/11) and 6.3%(1/16) in single instillation group and repeated instillation group respectively. And it is suggested that repeated instillation better than single instillation.2. Meta-analysis Eight trials were analyzed with a total of 979 patients. The bladder cancer incidence rate was 20.7%(108/521) in patients with intravesical instillation chemotherapy after nephroureterectomy. and 36.9%(169/458) without the intravesical chemotherapy after nephroureterectomy. Compared with those who didn’t receive instillation, the pooled OR of intravesical recurrence was 0.45 (95% CI 0.34-0.61,P< 0.001) in instillation patients. Subgroup analysis revealed that single instillation pooled OR was 0.48 (95% CI 0.28-0.83. P=0.009), ≧5 times instillation group pooled OR was 0.45 (95% CI 0.28-0.74. P=0.002). There was no significant difference between the two groups (P= 0.852).Conclusion This study demonstrates that prophylactic intravesical instillation chemotherapy could prevent bladder cancer recurrence in patients with primary UTUC after RNU. Although single instillation effect may be similar to repeated instillation, clinical results suggest that repeated instillation can’t be replaced by single instillation. There are some limitations for this study, so intravesical chemotherapy schedule is needed to be further studied by high quality trials.
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