Adjuvant chemotherapy after radical nephroureterectomy improves the survival outcome of high-risk upper tract urothelial carcinoma patients with cardiovascular comorbidity

This prospective randomized comparative trial study aimed to evaluate the therapeutic outcomes of radical nephroureterectomy and adjuvant chemotherapy (ACT) used in combination in high risk upper tract urothelial carcinoma (UTUC) patients with cardiovascular comorbidity. Based on the inclusion criteria of high-risk UTUC in EAU guidelines (updated in 2014), all eligible patients treated in our hospital from January 2014 to March 2018 were included, and cases with late disease, renal dysfunction, severe cardiopulmonary disease or other malignant tumors were excluded. The cases were randomized into two groups based on treatment regimen. Multivariate analyses were performed to analyze the influencing factors of survival outcome in the enrolled patients. The Cox proportional-hazards model and the Kaplan-Meier method were employed to assess progression free survival (PFS), overall survival (OS) and cancer specific survival (CSS). In addition, the potential adverse effects of chemotherapy were actively monitored. A total of 176 high-risk UTUC individuals with cardiovascular comorbidity were enrolled and evaluated in this study. Median follow-up durations were 30 months (range 6-54) in the RNU (n=82) group and 36 months (range 6-54) in the RNU+ACT (n=94) group. Multivariable analysis indicated that peri-operative cardiovascular events risk grade was independent prognostic factor for OS. Tumor size was independent prognostic factor for PFS and CSS. BMI and lymphovacular invasion were significant predictors of PFS. Clinical stage, lymph node involvement, and tumor grade were significant predictors of PFS, OS and CSS in these patients. Especially, chemotherapy was helpful in improving PFS [P<0.001, HR=6.327 (5.115-7.793)], OS [P=0.013, HR=2.336 (1.956-2.883)] and CSS [P=0.008, HR=3.073 (2.533-3.738)]. Kaplan-Meier analysis demonstrated that the oncologic outcomes of RNU treated high-risk UTUC patients were improved much significantly by ACT, including PFS [P=0.0033, HR=3.78 (3.13-4.55)], OS [P=0.0397, HR=1.39 (1.01-1.75)] and CSS [P=0.0255, HR=1.26 (1.07-1.45)]. Further analysis of the lymph node positive subgroup showed that the median time of oncologic events was enhanced in RNU+ACT treated individuals in comparison with the RNU group, including PFS (11.4 months vs. 31.9 months, P=0.0018), OS (26.8 months vs. 36.3 months, P=0.0255) and CSS (28.2 months vs. 39.3 months, P=0.0197). In the T3/4 cohort, significantly increased median PFS (13.9 months vs. 36.3 months, P=0.0217), OS (20.6 months vs. 32.2 months, P=0.0183) and CSS (21.9 months vs. 38.4 months, P=0.0226) were obtained in the combination group. Additionally, no severe adverse events (over grade 4) associated with chemotherapy were detected in the RNU+ACT group. In conclusion, ACT after radical surgery has statistically significant therapeutic effects on PFS, OS and CSS in high-risk UTUC patients with cardiovascular comorbidity.