TY - JOUR
T1 - Neoadjuvant versus adjuvant chemotherapy for upper tract urothelial carcinoma
AU - Martini, Alberto
AU - Falagario, Ugo Giovanni
AU - Waingankar, Nikhil
AU - Daza, Jorge
AU - Treacy, Patrick Julien
AU - Necchi, Andrea
AU - Galsky, Matthew D.
AU - Sfakianos, John P.
N1 - Publisher Copyright:
© 2020 Elsevier Inc.
PY - 2020/8
Y1 - 2020/8
N2 - 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.
AB - 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.
KW - Adjuvant chemotherapy
KW - Neoadjuvant chemotherapy
KW - Overall survival
KW - Radical nephroureterectomy
KW - Urothelial carcinoma
UR - http://www.scopus.com/inward/record.url?scp=85083061044&partnerID=8YFLogxK
U2 - 10.1016/j.urolonc.2020.03.008
DO - 10.1016/j.urolonc.2020.03.008
M3 - Article
C2 - 32284255
AN - SCOPUS:85083061044
SN - 1078-1439
VL - 38
SP - 684.e9-684.e15
JO - Urologic Oncology: Seminars and Original Investigations
JF - Urologic Oncology: Seminars and Original Investigations
IS - 8
ER -