Objective: Prognostic epigenetic biomarkers and clinical factors in upper tract urothelial carcinoma(UTUC)are inconclusive.We conducted this study to identify gene promoter(ABCC6,BRCA1,CDH1,GDF15,HSPA2,RASSF1A,SALL3,THBS1,TMEFF2 and VIM)methylation status and clinical predictors for UTUC patients(N=687).Methods: Using methylation-sensitive polymerase(MSP)chain reaction,we examined 10-gene promoter methylation status in 687 UTUC patients.The log-rank test and Cox regression were applied,and two nomograms were utilized to construct the prognostic model for cancer specific survival(CSS)and bladder recurrence free survival(BRFS),respectively.Results: Methylation in tumor tissue was detected in 14.3%for ABCC6,17.3%for BRCA1,14.3%for CDH1,49.9%for GDF15,41.2%for HSPA2,26.6%for RASSF1A,34.4%for SALL3,25.2%for THBS1,43.2%for TMEFF2 and 63.2%for VIM.A methylated promoter of CDH1(P=0.045),HSPA2(P<0.001)and RASSF1A(P=0.037)was significantly associated with a higher tumor stage(T3 and T4).A methylated promoter of BRCA1(P=0.013),HSPA2(P=0.030),RASSF1A(P=0.031)and THBS1(P=0.001);and an unmethylated promoter of GDF15(P<0.001)were significantly associated with tumor grade 3.A methylated promoter of RASSF1A(P=0.005)was associated with pN+.Older age(P<0.001),male sex(P=0.033),tumor muhifocality(P=0.008),ipsilateral hydronephrosis(P<0.001),larger main tumor diameter(5 cm,P<0.001),higher tumor stage(P<0.001),positive N status(P=0.018),methylated TMEFF2 promoter(P=0.002)and unmethylated BRCA1 promoter(P=0.004)were significantly associated with poor CSS.Tumor multifocality(P=0.002),ureteroscopy history(P=0.001),lower tumor grade(P=0.046),unmethylated promoter of GDF15(P=0.030)and RASSF1A(P=0.001)were considered as predictors to develop bladder recurrence after surgery.Conclusions: Methylation occurs commonly in UTUCs,may affect carcinogenic mechanisms,and is a well predictive factor for CSS and BR in UTUCs.