Neoadjuvant versus adjuvant chemotherapy for upper tract urothelial carcinoma.

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.

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.

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.

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.

Urologic oncology. 2020 Apr 10 [Epub ahead of print]

Alberto Martini, Ugo Giovanni Falagario, Nikhil Waingankar, Jorge Daza, Patrick Julien Treacy, Andrea Necchi, Matthew D Galsky, John P Sfakianos

Department of Urology, Icahn School of Medicine at Mount Sinai, NY; Department of Urology, Vita-Salute San Raffaele University, Milan, Italy. Electronic address: ., Department of Urology, Icahn School of Medicine at Mount Sinai, NY., Department of Urology, Icahn School of Medicine at Mount Sinai, NY; Institute for Healthcare Delivery Science, Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, NY., Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy., Division of Hematology and Oncology, Department of Medicine, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, NY.