Impact of Neoadjuvant Chemotherapy for Upper Tract Urothelial Carcinoma: A Population Based Analysis

Abstract

BACKGROUND AND OBJECTIVES: We examined pathologic complete response (pCR) and pathologic downstaging (pDS) rates after neoadjuvant chemotherapy (NAC) in high-risk upper tract urothelial carcinoma, as well as their predictors. We further sought to determine their effects on overall survival and examine prognosticators of survival after NAC. METHODS: The National Cancer Database was used to identify all patients from 2004 to 2016 with nonmetastatic high grade upper tract urothelial carcinoma who received NAC followed by nephroureterectomy. pCR and pDS rates were examined, and univariate and multivariate logistic regression was performed to identify clinical predictors. Kaplan-Meier and Cox proportional hazard methods were used to estimate overall survival. RESULTS: 309 patients met inclusion criteria. 27 patients (8.74% ) had pCR, and 92 (29.77% ) had pDS. pCR and pDS rates for N+ subgroup were 6.82% and 47.73% respectively, and for N0 subgroup, 9.50% and 22.62%. Female sex (OR 2.94, p = 0.010) was the only predictor of pCR. Node-positive disease (cN1 vs. cN0: OR 6.40, p < 0.001; cN2 vs. cN0: OR 7.46, p < 0.001) was a positive predictor of pDS, and the presence of lymphovascular invasion (LVI) (OR 0.14, p < 0.001) was a negative predictor of pDS. The median OS for all patients was 45.5 months. pCR and pDS were both associated with improved OS, (p < 0.001 for both); median was 99.1 months for both. LVI was the strongest negative prognostic factor for OS (HR 2.85, p < 0.001). CONCLUSIONS: Overall pathological complete response and downstaging rates were 8.74% and 29.77% respectively after multi-agent neoadjuvant chemotherapy. Node-negative and node-positive disease had equivalent rates of complete response, but node-positive disease had a significantly higher rate of downstaging. The presence of LVI was associated with worse overall survival.

Role of Neoadjuvant Chemotherapy on Pathological, Functional, and Survival Outcomes of Upper Tract Urothelial Carcinoma Patients: A Systematic Review and Meta-Analysis

“…Compared to the control group, the NAC group was associated with a significantly lower risk of advanced disease [6 studies, logOR = −0.81; 95% CI, −1.51-0.11] ( Figure 4 ). Significant heterogeneity was observed [ I 2 = 94.18%, P = .001]; however, the leave-one-out sensitivity analysis revealed that the studies of Almassi et al 12 and Venkat et al 29 were the main contributors to the observed heterogeneity ( Supplementary Figure 3 ).…”