The Impact of Neoadjuvant Chemotherapy on Cancer Specific Mortality in Patients With Upper Tract Urothelial Carcinoma: A Retrospective Analysis of an Other Cause Mortality Risk Matched Cohort

Purpose: Although neoadjuvant chemotherapy (NAC) may benefit upper tract urothelial carcinoma (UTUC) treatment, most studies are retrospective and affected by selection bias, as healthier patients are more likely to receive NAC. We therefore aimed to investigate NAC’s impact on cancer specific mortality (CSM) in an other-cause mortality (OCM) matched cohortMethods: The Surveillance, Epidemiology, and End Results database was queried to identify patients with histological diagnosis of UTUC (pT1-4N0-3M0) at radical nephoureterectomy (RNU) between 2007–2021. Patients who underwent systemic therapy before RNU were classified as having received NAC. Cox regression was used to calculate the 5 year-OCM risk, which was used to construct a 1:3 propensity-score matched cohort. Then, in the matched cohort, we performed competing risk regression analysis to investigate the impact of NAC on CSM.Results: We included 4,936 patients, 388 (7.9%) of whom underwent NAC. Median (interquartile range) age at diagnosis was 72 (64–79) years. The 5-year OCM rate was 26.4% versus 37.1% (p=0.004) in patients who received NAC men versus in those who did not receive NAC, but that difference became not statistically significant after matching (p=0.9). The standardized mean difference was 0.0003 for OCM risk, indicating a good match. In the matched cohort, patients in the NAC-group were more likely to be younger (67 vs. 73, p<0.0001), to be diagnosed more recently (2018 vs. 2015, p<0.0001) and to have a pN+UTUC (28.8% vs. 12.3%, p<0.0001), compared to no-NAC group. At MVA analysis, patients who did not undergo NAC had a significantly higher CSM-risk (hazard ratio,1.78; 95% confidence interval, 1.27–2.51; p<0.01), than their counterpart who received NAC.Conclusion: Compared to patients who did not receive NAC, those who received NAC seems to have a reduced CSM-risk for UTUC, when matched with their calculated OCM-risk. However, to establish it as the optimal treatment strategy for UTUC, additional prospective randomized studies are needed.