Background: Presently, no level I evidence is available to support the use of neoadjuvant chemotherapy (N)(AC) in patients diagnosed with high-grade upper tract urothelial carcinoma (UTUC). We aimed to compare outcomes of patients treated with radical nephroureterectomy (RNU) who received NAC vs. those who received AC.
Methods: The National Cancer Database was queried for UTUC patients with cT2-4N0M0 disease treated with RNU and NAC or AC. The role of NAC or AC on overall survival (OS) was evaluated by means of a multivariable Cox regression. Time to death was evaluated from diagnosis.
Results: Overall, 936 patients were identified, 128 (14%) received NAC whereas 808 (86%) received AC. No difference was observed between NAC vs. AC in terms of OS (P = 0.9). When sub-stratifying patients who received NAC in responders (cT>pT, given pN0; n = 46 [36%]) vs. nonresponders (n = 82 [64%]), we found that, relatively to AC, the subgroup of patients who did not respond to NAC had higher risk of dying from any cause (hazard ratio [HR]: 1.41; 95% confidence interval [CI]: 1.03,1.91; P = 0.03), whereas the sub-group who responded to NAC had better OS (HR: 0.45; 95% CI: 0.24,0.85; P = 0.01). The 5-year OS rates for responders to NAC vs. nonresponders vs. AC were: 71% vs. 26% vs. 43%, respectively. A landmark analysis fitted at 6 months after diagnosis, including 903 patients (NAC: 126 vs. AC: 777) confirmed our findings.
Conclusion: while we found no difference in outcomes between NAC vs. AC in high-grade UTUC, we found a hypothesis-generating association between survival and response to NAC. Further studies aimed at identifying potential responders to NAC are warranted.
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