Acknowledging these limitations in the existing literature, we sought to examine the impact of NAC on pathologic outcomes in patients with UTUC undergoing RNU or segmental ureterectomy on a national level. Using data from the National Cancer Database, which captures approximately 70% of newly diagnosed cancers in the United States, we identified a cohort of 6174 patients with non-metastatic UTUC who underwent RNU or segmental ureterectomy from 2006 – 2014.
Two-hundred sixty patients (4.2% of the cohort) received NAC, with increasing NAC utilization observed over the study period from 1.9% in 2006 to 7.1% in 2014. Patients receiving NAC were younger (median age 67.5 vs. 73 years) and had a higher frequency of clinical T2-4 stage (47% vs. 29%), reflecting the biases inherent to selecting patients for NAC before extirpative surgery. Defining pathologic response as a pathologic stage less than the clinical stage, we observed a higher incidence of pathologic response among patients receiving NAC (25.2% vs. 1.8%), including complete pathologic response (pT0) in 6% of patients receiving NAC. On multivariable logistic regression analysis, NAC was independently associated with pathologic response (odds ratio 19.8, 95% confidence interval 11.8 – 33.5).
The results of this analysis of national registry data reflecting ‘real world’ practice provide further evidence supporting the benefit of NAC in pathologic down-staging in patients with high-grade UTUC undergoing extirpative surgery. The decision to administer neoadjuvant versus adjuvant chemotherapy is especially important in UTUC, given that renal functional decline after RNU can render up to 61% of patients cisplatin-ineligible, based on prior studies. Although the recent phase III POUT trial demonstrated significantly improved disease-free survival with adjuvant platinum-based chemotherapy in locally advanced UTUC (pT2-T4 N0-3), 38% of patients in that trial were cisplatin-ineligible after RNU (Birtle, et al. GU ASCO Symposium 2018). These inherent limitations to adjuvant chemotherapy make NAC an appealing alternative for UTUC. While the recently-reported single arm phase II trial (ECOG-ACRIN 8141) provided additional data suggesting a pathologic response in a proportion of patients with NAC, additional prospective (ideally randomized) trials are needed to better define the impact of NAC on clinical outcomes in UTUC.
Written by: Nima Almassi, MD1, and Petros Grivas, MD, PhD2
1Glickman Urological and Kidney Institute and Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH
2University of Washington, Fred Hutchinson Cancer Research Center, Seattle, WA
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