Oncologic Outcomes in Patients with Residual Upper Tract Urothelial Carcinoma Following Neoadjuvant Chemotherapy
Sean A Fletcher1, Maximilian Pallauf2, Emelia K Watts3
1The James Buchanan Brady Urological Institute and Department of Urology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Background And Objective:
Growing evidence supports the use of neoadjuvant chemotherapy (NAC) for upper tract urothelial carcinoma (UTUC). However, the implications of residual UTUC at radical nephroureterectomy (RNU) after NAC are not well characterized. Our objective was to compare oncologic outcomes for pathologic risk-matched patients who underwent RNU for UTUC who either received NAC or were chemotherapy-naïve.
Methods:
We retrospectively identified 1993 patients (including 112 NAC recipients) who underwent RNU for nonmetastatic, high-grade UTUC between 1985 and 2022 in a large, international, multicenter cohort. We divided the cohort into low-risk and high-risk groups defined according to pathologic findings of muscle invasion and lymph node involvement at RNU. Recurrence-free survival (RFS), overall survival (OS), and cancer-specific survival (CSS) estimates were calculated using the Kaplan-Meier method. Multivariable analyses were performed to determine clinical and demographic factors associated with these outcomes.
Key Findings And Limitations:
Among patients with low-risk pathology at RNU, RFS, OS, and CSS were similar between the NAC and chemotherapy-naïve groups. Among patients with high-risk pathology at RNU, the NAC group had poorer RFS (hazard ratio [HR] 3.07, 95% confidence interval [CI] 2.10-4.48), OS (HR 2.06, 95% CI 1.33-3.20), and CSS (subdistribution HR 2.54, 95% CI 1.37-4.69) in comparison to the pathologic risk-matched, chemotherapy-naïve group. Limitations include the lack of centralized pathologic review.
Conclusions And Clinical Implications:
Patients with residual invasive disease at RNU after NAC represent a uniquely high-risk population with respect to oncologic outcomes. There is a critical need to determine an optimal adjuvant approach for these patients.
Patient Summary:
We studied a large, international group of patients with cancer of the upper urinary tract who underwent surgery either with or without receiving chemotherapy beforehand. We identified a high-risk subgroup of patients with residual aggressive cancer after chemotherapy and surgery who should be prioritized for clinical trials and drug development.
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