Malte Rieken1, Evanguelos Xylinas2, Luis Kluth3, Joseph J Crivelli4, James Chrystal4, Talia Faison4, Yair Lotan5, Pierre I Karakiewicz6, Maxine Sun6, Harun Fajkovic7, Marek Babjuk8, Alexander Bachmann9, Douglas S Scherr4, Shahrokh F Shariat10. 1. Department of Urology, Weill Cornell Medical College, New York-Presbyterian Hospital, New York, NY; Department of Urology, University Hospital Basel, Basel, Switzerland. 2. Department of Urology, Weill Cornell Medical College, New York-Presbyterian Hospital, New York, NY; Department of Urology Cochin Hospital, APHP, Paris Descartes University, Paris, France. 3. Department of Urology, Weill Cornell Medical College, New York-Presbyterian Hospital, New York, NY; Department of Urology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. 4. Department of Urology, Weill Cornell Medical College, New York-Presbyterian Hospital, New York, NY. 5. Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX. 6. Department of Urology, University of Montreal, Montreal, Quebec, Canada. 7. Department of Urology, Medical University of Vienna, Vienna, Austria. 8. Department of Urology, Hospital Motol, Second Faculty of Medicine, Charles University, Praha, Czech Republic. 9. Department of Urology, University Hospital Basel, Basel, Switzerland. 10. Department of Urology, Weill Cornell Medical College, New York-Presbyterian Hospital, New York, NY; Division of Medical Oncology, Weill Cornell Medical College, New York-Presbyterian Hospital, New York, NY; Department of Urology, Medical University of Vienna, Vienna, Austria. Electronic address: sfshariat@gmail.com.
Abstract
OBJECTIVES: Evidence suggests a positive effect of metformin on cancer incidence and outcome. To date, the effect of metformin use on prognosis in urothelial carcinoma of the bladder (UCB) remains uninvestigated. We tested the hypothesis that metformin use affects oncologic outcomes of patients treated with radical cystectomy for UCB. METHODS AND MATERIALS: We retrospectively evaluated 1,502 patients treated at 4 institutions with radical cystectomy and pelvic lymphadenectomy without neoadjuvant therapy. Cox regression models addressed the association of diabetes mellitus (DM) and metformin use with disease recurrence, cancer-specific mortality, and any-cause mortality. RESULTS: A total of 200 patients (13.3%) had DM, 80 patients (5.3%) used metformin. Within a median follow-up of 34 months, 509 patients (33.9%) experienced disease recurrence, 402 patients (26.8%) died of UCB, and 551 patients (36.7%) died from any cause. In univariable Cox regression analyses, DM without metformin use was associated with increased risk of disease recurrence (hazard ratio [HR]: 1.40, 95% confidence interval [CI] 1.05-1.87, P = 0.02), cancer-specific mortality (HR: 1.60, 95% CI 1.17-2.17, P = 0.003), and any-cause mortality (HR: 1.55, 95% CI 1.18-2.03, P = 0.002), whereas metformin use was associated with decreased risk of disease recurrence (HR: 0.61, 95% CI 0.37-0.98, P = 0.04), cancer-specific mortality (HR: 0.56, 95% CI 0.33-0.97, P = 0.04), and any-cause mortality (HR: 0.54, 95% CI 0.33-0.88, P = 0.01). In multivariable Cox regression analyses, DM treated without metformin use remained associated with worse cancer-specific mortality (HR: 1.53, 95% CI 1.12-2.09, P = 0.007) and any-cause mortality (HR: 1.52, 95% CI 1.16-2.00, P = 0.003) but not disease recurrence. CONCLUSIONS: Diabetic patients who do not use metformin appear to be at higher risk of cancer-specific and any-cause mortality than patients without DM. It remains unclear, whether the severity of DM in this group of patients or the use of metformin itself affects outcomes of UCB. The mechanisms behind the effect of DM on patients with UCB and the potential protective effect of metformin need further elucidation.
OBJECTIVES: Evidence suggests a positive effect of metformin on cancer incidence and outcome. To date, the effect of metformin use on prognosis in urothelial carcinoma of the bladder (UCB) remains uninvestigated. We tested the hypothesis that metformin use affects oncologic outcomes of patients treated with radical cystectomy for UCB. METHODS AND MATERIALS: We retrospectively evaluated 1,502 patients treated at 4 institutions with radical cystectomy and pelvic lymphadenectomy without neoadjuvant therapy. Cox regression models addressed the association of diabetes mellitus (DM) and metformin use with disease recurrence, cancer-specific mortality, and any-cause mortality. RESULTS: A total of 200 patients (13.3%) had DM, 80 patients (5.3%) used metformin. Within a median follow-up of 34 months, 509 patients (33.9%) experienced disease recurrence, 402 patients (26.8%) died of UCB, and 551 patients (36.7%) died from any cause. In univariable Cox regression analyses, DM without metformin use was associated with increased risk of disease recurrence (hazard ratio [HR]: 1.40, 95% confidence interval [CI] 1.05-1.87, P = 0.02), cancer-specific mortality (HR: 1.60, 95% CI 1.17-2.17, P = 0.003), and any-cause mortality (HR: 1.55, 95% CI 1.18-2.03, P = 0.002), whereas metformin use was associated with decreased risk of disease recurrence (HR: 0.61, 95% CI 0.37-0.98, P = 0.04), cancer-specific mortality (HR: 0.56, 95% CI 0.33-0.97, P = 0.04), and any-cause mortality (HR: 0.54, 95% CI 0.33-0.88, P = 0.01). In multivariable Cox regression analyses, DM treated without metformin use remained associated with worse cancer-specific mortality (HR: 1.53, 95% CI 1.12-2.09, P = 0.007) and any-cause mortality (HR: 1.52, 95% CI 1.16-2.00, P = 0.003) but not disease recurrence. CONCLUSIONS:Diabeticpatients who do not use metformin appear to be at higher risk of cancer-specific and any-cause mortality than patients without DM. It remains unclear, whether the severity of DM in this group of patients or the use of metformin itself affects outcomes of UCB. The mechanisms behind the effect of DM on patients with UCB and the potential protective effect of metformin need further elucidation.
Authors: Maria E Goossens; Frank Buntinx; Maurice P Zeegers; J H M Driessen; Marie L De Bruin; Frank De Vries Journal: Br J Clin Pharmacol Date: 2015-10-28 Impact factor: 4.335
Authors: Patrick O Richard; Ardalan E Ahmad; Shaheena Bashir; Alexandre Zlotta; Bimal Bhindi; Ricardo Leao; Madhur Nayan; Aza Mohammed; Neil E Fleshner; Girish S Kulkarni Journal: Can Urol Assoc J Date: 2018-02-23 Impact factor: 1.862
Authors: Bartosz Dybowski; Krzysztof Ossoliński; Anna Ossolińska; Michał Peller; Ewa Bres-Niewada; Piotr Radziszewski Journal: Cent European J Urol Date: 2015-10-15