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Comparative effectiveness of neoadjuvant chemotherapy in bladder and upper urinary tract urothelial carcinoma

D. D'Andrea, S. Matin, PC. Black, FG. Petros, H. Zargar, CP. Dinney, MS. Cookson, W. Kassouf, MA. Dall'Era, JS. McGrath, JL. Wright, AC. Thorpe, TM. Morgan, JM. Holzbeierlein, TJ. Bivalacqua, SS. Sridhar, S. North, DA. Barocas, Y. Lotan, AJ....

. 2021 ; 127 (5) : 528-537. [pub] 20201014

Language English Country Great Britain

Document type Journal Article

OBJECTIVE: To assess the differential response to neoadjuvant chemotherapy (NAC) in patients with urothelial carcinoma of the bladder (UCB) compared to upper tract urothelial carcioma (UTUC) treated with radical surgery. PATIENTS AND METHODS: Data from 1299 patients with UCB and 276 with UTUC were obtained from multicentric collaborations. The association of disease location (UCB vs UTUC) with pathological complete response (pCR, defined as a post-treatment pathological stage ypT0N0) and pathological objective response (pOR, defined as ypT0-Ta-Tis-T1N0) after NAC was evaluated using logistic regression analyses. The association with overall (OS) and cancer-specific survival (CSS) was evaluated using Cox regression analyses. RESULTS: A pCR was found in 250 (19.2%) patients with UCB and in 23 (8.3%) with UTUC (P < 0.01). A pOR was found in 523 (40.3%) patients with UCB and in 133 (48.2%) with UTUC (P = 0.02). On multivariable logistic regression analysis, patients with UTUC were less likely to have a pCR (odds ratio [OR] 0.45, 95% confidence interval [CI] 0.27-0.70; P < 0.01) and more likely to have a pOR (OR 1.57, 95% CI 1.89-2.08; P < 0.01). On univariable Cox regression analyses, UTUC was associated with better OS (hazard ratio [HR] 0.80, 95% CI 0.64-0.99, P = 0.04) and CSS (HR 0.63, 95% CI 0.49-0.83; P < 0.01). On multivariable Cox regression analyses, UTUC remained associated with CSS (HR 0.61, 95% CI 0.45-0.82; P < 0.01), but not with OS. CONCLUSIONS: Our present findings suggest that the benefit of NAC in UTUC is similar to that found in UCB. These data can be used as a benchmark to contextualise survival outcomes and plan future trial design with NAC in urothelial cancer.

Department of Genitourinary Oncology H Lee Moffitt Cancer Center and Research Institute Tampa FL USA

Department of Medical Oncology and Hematology Princess Margaret Cancer Center Toronto ON Canada

Department of Oncology Cross Cancer Institute University of Alberta Edmonton AB Canada

Department of Urologic Sciences University of British Columbia Vancouver BC Canada

Department of Urologic Surgery Vanderbilt University Medical Center Nashville TN USA

Department of Urology 2nd Faculty of Medicine Charles University Prag Czech Republic

Department of Urology and Kidney Transplant Eleanor N Dana Cancer Center The University of Toledo Medical Center Toledo OH USA

Department of Urology Center and The Stephenson Cancer Center The University of Oklahoma Health Sciences Oklahoma City OK USA

Department of Urology Comprehensive Cancer Center Medical University of Vienna Vienna Austria

Department of Urology Davis Medical Center University of California at Davis Sacramento CA USA

Department of Urology Freeman Hospital Newcastle Upon Tyne UK

Department of Urology MD Anderson Cancer Center Houston TX USA

Department of Urology The Johns Hopkins School of Medicine The James Buchanan Brady Urological Institute Baltimore MD USA

Department of Urology The Netherlands Cancer Institute Antoni van Leeuwenhoek Hospital Amsterdam The Netherlands

Department of Urology University of Jordan Amman Jordan

Department of Urology University of Kansas Medical Center Kansas City KS USA

Department of Urology University of Michigan Health System Ann Arbor MI USA

Department of Urology University of Texas Southwestern Medical Center Dallas TX USA

Department of Urology University of Washington Seattle WA USA

Department of Urology USC Norris Comprehensive Cancer Center University of Southern California Los Angeles CA USA

Department of Urology Western Health Melbourne Vic Australia

Departments of Urology Weill Cornell Medical College New York NY USA

Division of Urology Department of Surgery McGill University Health Center Montreal QC Canada

European Association of Urology Research Foundation Arnhem The Netherlands

Glickman Urological and Kidney Institute Cleveland Clinic Cleveland OH USA

Institute for Urology and Reproductive Health 1 M Sechenov 1st Moscow State Medical University Moscow Russia

References provided by Crossref.org

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$a OBJECTIVE: To assess the differential response to neoadjuvant chemotherapy (NAC) in patients with urothelial carcinoma of the bladder (UCB) compared to upper tract urothelial carcioma (UTUC) treated with radical surgery. PATIENTS AND METHODS: Data from 1299 patients with UCB and 276 with UTUC were obtained from multicentric collaborations. The association of disease location (UCB vs UTUC) with pathological complete response (pCR, defined as a post-treatment pathological stage ypT0N0) and pathological objective response (pOR, defined as ypT0-Ta-Tis-T1N0) after NAC was evaluated using logistic regression analyses. The association with overall (OS) and cancer-specific survival (CSS) was evaluated using Cox regression analyses. RESULTS: A pCR was found in 250 (19.2%) patients with UCB and in 23 (8.3%) with UTUC (P < 0.01). A pOR was found in 523 (40.3%) patients with UCB and in 133 (48.2%) with UTUC (P = 0.02). On multivariable logistic regression analysis, patients with UTUC were less likely to have a pCR (odds ratio [OR] 0.45, 95% confidence interval [CI] 0.27-0.70; P < 0.01) and more likely to have a pOR (OR 1.57, 95% CI 1.89-2.08; P < 0.01). On univariable Cox regression analyses, UTUC was associated with better OS (hazard ratio [HR] 0.80, 95% CI 0.64-0.99, P = 0.04) and CSS (HR 0.63, 95% CI 0.49-0.83; P < 0.01). On multivariable Cox regression analyses, UTUC remained associated with CSS (HR 0.61, 95% CI 0.45-0.82; P < 0.01), but not with OS. CONCLUSIONS: Our present findings suggest that the benefit of NAC in UTUC is similar to that found in UCB. These data can be used as a benchmark to contextualise survival outcomes and plan future trial design with NAC in urothelial cancer.
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