Sebastiano Nazzani1,2,3, Felix Preisser4,5,6, Elio Mazzone4,5,7, Zhe Tian5, Francesco A Mistretta8, Shahrokh F Shariat9, Denis Soulières5, Fred Saad5, Emanuele Montanari10, Stefano Luzzago10, Alberto Briganti7, Luca Carmignani11, Pierre I Karakiewicz4,5. 1. Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Center, Montreal, QC, Canada. sebastiano.nazzani@yahoo.com. 2. Centre de recherche du Centre Hospitalier de l'Université de Montréal (CR-CHUM) and Institut du cancer de Montréal, Montréal, QC, Canada. sebastiano.nazzani@yahoo.com. 3. Academic Department of Urology, IRCCS Policlinico San Donato, University of Milan, Corso San Gottardo 12, Milano MI, Italy. sebastiano.nazzani@yahoo.com. 4. Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Center, Montreal, QC, Canada. 5. Centre de recherche du Centre Hospitalier de l'Université de Montréal (CR-CHUM) and Institut du cancer de Montréal, Montréal, QC, Canada. 6. Martini-Klinik Prostate Cancer Center, University Hospital Hamburg-Eppendorf, Hamburg, Germany. 7. Division of Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Vita-Salute San Raffaele University, Milan, Italy. 8. Department of Urology, Istituto Europeo di Oncologia, Milan, Italy. 9. Department of Urology, Medical University of Vienna, Vienna, Austria. 10. Department of Urology, IRCCS Fondazione Ca' Granda-Ospedale Maggiore Policlinico University of Milan, Milan, Italy. 11. Academic Department of Urology, IRCCS Policlinico San Donato, University of Milan, Corso San Gottardo 12, Milano MI, Italy.
Abstract
OBJECTIVES: To analyze the potential survival benefit of perioperative chemotherapy (CHT) in patients treated with nephroureterectomy (NU) for non-metastatic locally advanced upper tract urothelial carcinoma. METHODS: Within the Surveillance, Epidemiology, and End Results database (2004-2014), we identified 1286 patients with T3 or T4, N 0-3 M0 UTUC. Kaplan-Meier plots, as well as multivariable Cox regression models (MCRMs) relying on inverse probability after treatment weighting (IPTW) and landmark analyses, were used to test the effect of CHT vs no CHT on overall mortality (OM) in the overall population (n =1286), as well as after stratification according to lymph node invasion (LNI). RESULTS: Overall, 37.4% patients received CHT. The CHT rate was higher with LNI (62.2% vs 35.2%, p < 0.001). In MCRMs, testing for OM in the overall population, CHT was associated with lower rates of OM (HR 0.71, CI 0.58-0.87; p = 0.001). Similarly, in MCRMs testing for OM in patients with LNI, CHT achieved independent predictor status for lower OM (HR 0.61, CI 0.48-0.78; p < 0.001). Conversely, in MCRMs testing for OM in patients without LNI, no CHT effect was recorded (HR 0.72, CI 0.52-1.01; p = 0.05). All results were confirmed after IPTW adjustment and in landmark analyses. CONCLUSIONS: Our results represent a contemporary North American report indicating lower OM after CHT for patients with locally advanced non-metastatic upper tract urothelial carcinoma, specifically in patients with T3-T4, N1-N3, M0 disease. Validation of the current and of the previous study is required within a randomized prospective design.
OBJECTIVES: To analyze the potential survival benefit of perioperative chemotherapy (CHT) in patients treated with nephroureterectomy (NU) for non-metastatic locally advanced upper tract urothelial carcinoma. METHODS: Within the Surveillance, Epidemiology, and End Results database (2004-2014), we identified 1286 patients with T3 or T4, N 0-3 M0 UTUC. Kaplan-Meier plots, as well as multivariable Cox regression models (MCRMs) relying on inverse probability after treatment weighting (IPTW) and landmark analyses, were used to test the effect of CHT vs no CHT on overall mortality (OM) in the overall population (n =1286), as well as after stratification according to lymph node invasion (LNI). RESULTS: Overall, 37.4% patients received CHT. The CHT rate was higher with LNI (62.2% vs 35.2%, p < 0.001). In MCRMs, testing for OM in the overall population, CHT was associated with lower rates of OM (HR 0.71, CI 0.58-0.87; p = 0.001). Similarly, in MCRMs testing for OM in patients with LNI, CHT achieved independent predictor status for lower OM (HR 0.61, CI 0.48-0.78; p < 0.001). Conversely, in MCRMs testing for OM in patients without LNI, no CHT effect was recorded (HR 0.72, CI 0.52-1.01; p = 0.05). All results were confirmed after IPTW adjustment and in landmark analyses. CONCLUSIONS: Our results represent a contemporary North American report indicating lower OM after CHT for patients with locally advanced non-metastatic upper tract urothelial carcinoma, specifically in patients with T3-T4, N1-N3, M0 disease. Validation of the current and of the previous study is required within a randomized prospective design.