Diabetes mellitus without metformin intake is associated with worse oncologic outcomes after radical nephroureterectomy for upper tract urothelial carcinoma

M. Rieken, E. Xylinas, L. Kluth, Q. D. Trinh, R. K. Lee, H. Fajkovic, G. Novara, Vitaly Margulis, Yair Lotan, J. I. Martinez-Salamanca, K. Matsumoto, C. Seitz, M. Remzi, P. I. Karakiewicz, D. S. Scherr, A. Briganti, A. Kautzky-Willer, A. Bachmann, S. F. Shariat

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Abstract

Aims Evidence suggests a detrimental effect of diabetes mellitus (DM) on cancer incidence and outcomes. To date, the effect of DM and its treatment on prognosis in upper tract urothelial carcinoma (UTUC) remains uninvestigated. We tested the hypothesis that DM and metformin use impact oncologic outcomes of patients treated with radical nephroureterectomy (RNU) for UTUC. Methods Retrospective analysis of 2492 patients with UTUC treated at 23 institutions with RNU without neoadjuvant therapy. Cox regression models addressed the association of DM and metformin use with disease recurrence, cancer-specific mortality and any-cause mortality. Results A total of 365 (14.3%) patients had DM and 194 (7.8%) patients used metformin. Within a median follow-up of 36 months, 663 (26.6%) patients experienced disease recurrence, 545 patients (21.9%) died of UTUC and 884 (35.5%) patients died from any cause. Diabetic patients who did not use metformin were at significantly higher risk of disease recurrence and cancer-specific death compared to non-diabetic patients and diabetic patients who used metformin. In multivariable Cox regression analyses, DM treated without metformin was associated with worse recurrence-free survival (HR: 1.44, 95% CI 1.10-1.90, p = 0.009) and cancer-specific mortality (HR: 1.49, 95% CI 1.11-2.00, p = 0.008). Conclusions Diabetic UTUC patients without metformin use have significantly worse oncologic outcomes than diabetics who used metformin and non-diabetics. The possible mechanism behind the impact of DM on UTUC biology and the potentially protective effect of metformin need further elucidation.

Original languageEnglish (US)
Pages (from-to)113-120
Number of pages8
JournalEuropean Journal of Surgical Oncology
Volume40
Issue number1
DOIs
StatePublished - Jan 2014

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Metformin
Diabetes Mellitus
Carcinoma
Recurrence
Mortality
Neoplasms
Neoadjuvant Therapy
Proportional Hazards Models
Regression Analysis

Keywords

  • Diabetes mellitus
  • Metformin
  • Surgery
  • Upper tract urothelial carcinoma

ASJC Scopus subject areas

  • Oncology
  • Surgery

Cite this

Diabetes mellitus without metformin intake is associated with worse oncologic outcomes after radical nephroureterectomy for upper tract urothelial carcinoma. / Rieken, M.; Xylinas, E.; Kluth, L.; Trinh, Q. D.; Lee, R. K.; Fajkovic, H.; Novara, G.; Margulis, Vitaly; Lotan, Yair; Martinez-Salamanca, J. I.; Matsumoto, K.; Seitz, C.; Remzi, M.; Karakiewicz, P. I.; Scherr, D. S.; Briganti, A.; Kautzky-Willer, A.; Bachmann, A.; Shariat, S. F.

In: European Journal of Surgical Oncology, Vol. 40, No. 1, 01.2014, p. 113-120.

Research output: Contribution to journalArticle

Rieken, M, Xylinas, E, Kluth, L, Trinh, QD, Lee, RK, Fajkovic, H, Novara, G, Margulis, V, Lotan, Y, Martinez-Salamanca, JI, Matsumoto, K, Seitz, C, Remzi, M, Karakiewicz, PI, Scherr, DS, Briganti, A, Kautzky-Willer, A, Bachmann, A & Shariat, SF 2014, 'Diabetes mellitus without metformin intake is associated with worse oncologic outcomes after radical nephroureterectomy for upper tract urothelial carcinoma', European Journal of Surgical Oncology, vol. 40, no. 1, pp. 113-120. https://doi.org/10.1016/j.ejso.2013.09.016
Rieken, M. ; Xylinas, E. ; Kluth, L. ; Trinh, Q. D. ; Lee, R. K. ; Fajkovic, H. ; Novara, G. ; Margulis, Vitaly ; Lotan, Yair ; Martinez-Salamanca, J. I. ; Matsumoto, K. ; Seitz, C. ; Remzi, M. ; Karakiewicz, P. I. ; Scherr, D. S. ; Briganti, A. ; Kautzky-Willer, A. ; Bachmann, A. ; Shariat, S. F. / Diabetes mellitus without metformin intake is associated with worse oncologic outcomes after radical nephroureterectomy for upper tract urothelial carcinoma. In: European Journal of Surgical Oncology. 2014 ; Vol. 40, No. 1. pp. 113-120.
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abstract = "Aims Evidence suggests a detrimental effect of diabetes mellitus (DM) on cancer incidence and outcomes. To date, the effect of DM and its treatment on prognosis in upper tract urothelial carcinoma (UTUC) remains uninvestigated. We tested the hypothesis that DM and metformin use impact oncologic outcomes of patients treated with radical nephroureterectomy (RNU) for UTUC. Methods Retrospective analysis of 2492 patients with UTUC treated at 23 institutions with RNU without neoadjuvant therapy. Cox regression models addressed the association of DM and metformin use with disease recurrence, cancer-specific mortality and any-cause mortality. Results A total of 365 (14.3{\%}) patients had DM and 194 (7.8{\%}) patients used metformin. Within a median follow-up of 36 months, 663 (26.6{\%}) patients experienced disease recurrence, 545 patients (21.9{\%}) died of UTUC and 884 (35.5{\%}) patients died from any cause. Diabetic patients who did not use metformin were at significantly higher risk of disease recurrence and cancer-specific death compared to non-diabetic patients and diabetic patients who used metformin. In multivariable Cox regression analyses, DM treated without metformin was associated with worse recurrence-free survival (HR: 1.44, 95{\%} CI 1.10-1.90, p = 0.009) and cancer-specific mortality (HR: 1.49, 95{\%} CI 1.11-2.00, p = 0.008). Conclusions Diabetic UTUC patients without metformin use have significantly worse oncologic outcomes than diabetics who used metformin and non-diabetics. The possible mechanism behind the impact of DM on UTUC biology and the potentially protective effect of metformin need further elucidation.",
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T1 - Diabetes mellitus without metformin intake is associated with worse oncologic outcomes after radical nephroureterectomy for upper tract urothelial carcinoma

AU - Rieken, M.

AU - Xylinas, E.

AU - Kluth, L.

AU - Trinh, Q. D.

AU - Lee, R. K.

AU - Fajkovic, H.

AU - Novara, G.

AU - Margulis, Vitaly

AU - Lotan, Yair

AU - Martinez-Salamanca, J. I.

AU - Matsumoto, K.

AU - Seitz, C.

AU - Remzi, M.

AU - Karakiewicz, P. I.

AU - Scherr, D. S.

AU - Briganti, A.

AU - Kautzky-Willer, A.

AU - Bachmann, A.

AU - Shariat, S. F.

PY - 2014/1

Y1 - 2014/1

N2 - Aims Evidence suggests a detrimental effect of diabetes mellitus (DM) on cancer incidence and outcomes. To date, the effect of DM and its treatment on prognosis in upper tract urothelial carcinoma (UTUC) remains uninvestigated. We tested the hypothesis that DM and metformin use impact oncologic outcomes of patients treated with radical nephroureterectomy (RNU) for UTUC. Methods Retrospective analysis of 2492 patients with UTUC treated at 23 institutions with RNU without neoadjuvant therapy. Cox regression models addressed the association of DM and metformin use with disease recurrence, cancer-specific mortality and any-cause mortality. Results A total of 365 (14.3%) patients had DM and 194 (7.8%) patients used metformin. Within a median follow-up of 36 months, 663 (26.6%) patients experienced disease recurrence, 545 patients (21.9%) died of UTUC and 884 (35.5%) patients died from any cause. Diabetic patients who did not use metformin were at significantly higher risk of disease recurrence and cancer-specific death compared to non-diabetic patients and diabetic patients who used metformin. In multivariable Cox regression analyses, DM treated without metformin was associated with worse recurrence-free survival (HR: 1.44, 95% CI 1.10-1.90, p = 0.009) and cancer-specific mortality (HR: 1.49, 95% CI 1.11-2.00, p = 0.008). Conclusions Diabetic UTUC patients without metformin use have significantly worse oncologic outcomes than diabetics who used metformin and non-diabetics. The possible mechanism behind the impact of DM on UTUC biology and the potentially protective effect of metformin need further elucidation.

AB - Aims Evidence suggests a detrimental effect of diabetes mellitus (DM) on cancer incidence and outcomes. To date, the effect of DM and its treatment on prognosis in upper tract urothelial carcinoma (UTUC) remains uninvestigated. We tested the hypothesis that DM and metformin use impact oncologic outcomes of patients treated with radical nephroureterectomy (RNU) for UTUC. Methods Retrospective analysis of 2492 patients with UTUC treated at 23 institutions with RNU without neoadjuvant therapy. Cox regression models addressed the association of DM and metformin use with disease recurrence, cancer-specific mortality and any-cause mortality. Results A total of 365 (14.3%) patients had DM and 194 (7.8%) patients used metformin. Within a median follow-up of 36 months, 663 (26.6%) patients experienced disease recurrence, 545 patients (21.9%) died of UTUC and 884 (35.5%) patients died from any cause. Diabetic patients who did not use metformin were at significantly higher risk of disease recurrence and cancer-specific death compared to non-diabetic patients and diabetic patients who used metformin. In multivariable Cox regression analyses, DM treated without metformin was associated with worse recurrence-free survival (HR: 1.44, 95% CI 1.10-1.90, p = 0.009) and cancer-specific mortality (HR: 1.49, 95% CI 1.11-2.00, p = 0.008). Conclusions Diabetic UTUC patients without metformin use have significantly worse oncologic outcomes than diabetics who used metformin and non-diabetics. The possible mechanism behind the impact of DM on UTUC biology and the potentially protective effect of metformin need further elucidation.

KW - Diabetes mellitus

KW - Metformin

KW - Surgery

KW - Upper tract urothelial carcinoma

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