Urothelial carcinomas are a heterogeneous group of cancers, including urinary bladder carcinoma and upper urinary tract urothelial carcinoma (UTUC). Recent evidence has suggested that preoperative renal insufficiency indicates poor prognosis in patients with muscle-invasive bladder cancer (MIBC) and UTUC [1-6]. However, the impact of preoperative renal impairment severity on prognosis in urothelial carcinoma remains unelucidated. In the present study, we compared oncological outcomes among patients with urothelial carcinoma with estimated glomerular filtration rate (eGFR) ≥60, 45≤eGFR<60 and eGFR<45 mL/min/1.73 m2. A total of 1066 patients with urothelial carcinoma who underwent radical cystectomy or nephroureterectomy at six medical centers during the period from February 1995 to November 2017 were retrospectively examined. Oncological outcomes, stratified using preoperative estimated glomerular filtration rate (eGFR≥60, 45≤eGFR<60 and eGFR<45 mL/min/1.73 m2), were investigated. Inverse probability of treatment weighting (IPTW)-adjusted Cox proportional hazards regression analysis was performed to evaluate the impact of preoperative eGFR on prognosis.
Of 610 patients with muscle-invasive bladder cancer, 80 (13%) had severe renal insufficiency (eGFR<45 mL/min/1.73 m2). Of 456 patients with upper tract urothelial carcinoma (UTUC), 101 (22%) had severe renal insufficiency. We observed significant differences were noted in background and prognosis among the patients with preoperative eGFR≥60, 45≤eGFR<60 and eGFR<45 mL/min/1.73 m2. Findings of IPTW-adjusted Cox regression analysis demonstrated that preoperative eGFR<45 mL/min/1.73 m2 was significantly associated with poor post-surgical recurrence-free, cancer-specific and overall survival rates in patients with either MIBC or UTUC.
As the prevalence of older age is higher among patients with urothelial carcinoma, studies report a recent increase in interest in the impact of preoperative renal insufficiency on poor prognosis [3-5, 7, 8]. Several studies have indicated an association between chronic kidney disease (CKD) and oncological outcomes associated with the effects of chronic inflammation, oxidative stress, metabolic disorder, uraemia-associated immune deficiency, and frailty [9-11]. However, an association between the severity of renal insufficiency and malignant potential in urothelial carcinoma remains to be established, and only a few studies have evaluated the impact of preoperative eGFR<45 mL/min/1.73 m2 on oncological outcomes in patient with urothelial carcinoma [6, 12]. Notably, this is the first study to compare the oncological outcomes between CKD stage 3A (45≤eGFR<60 mL/min/1.73 m2) and 3B (eGFR<45 mL/min/1.73 m2). Although the impact of CKD on prognosis in urothelial carcinoma has been suggested, CKD is not an independent risk factor for survival in patients with several cancers. Head and neck, stomach, liver, colorectal, urinary tract, gynecological and haematologic malignancies have been reported to be associated with CKD and poor prognosis . However, biological mechanisms underlying the association among CKD, cancer type and oncological outcomes remain unelucidated. Further research is required for clarification of the mechanisms underlying carcinogenesis and CKD and for the determination of the prognostic utility of CKD in selected types of cancer.
Several limitations of the present study must be acknowledged. First, we were unable to control for selection bias and other unmeasurable confounders due to the retrospective study design. Despite these limitations, the results of this study support the rationale that preoperative eGFR<45 mL/min/1.73 m2 itself is an important predictor of cancer mortality in patients with urothelial carcinoma.
Written by: Shingo Hatakeyama, MD. Ph.D, Assistant Professor, Department of Urology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
 Li CELi CE, Chien CS, Chuang YC, Chang YI, Tang HP, Kang CH. Chronic kidney disease as an important risk factor for tumor recurrences, progression and overall survival in primary non-muscle-invasive bladder cancer. Int Urol Nephrol. 2016;48:993-9.
 Thrasher JB, Frazier HA, Robertson JE, Dodge RK, Paulson DF. Clinical variables which serve as predictors of cancer-specific survival among patients treated with radical cystectomy for transitional cell carcinoma of the bladder and prostate. Cancer. 1994;73:1708-15.
 Cao J, Zhao X, Zhong Z, Zhang L, Zhu X, Xu R. Prognostic Value of Pre-operative Renal Insufficiency in Urothelial Carcinoma: A Systematic Review and Meta-Analysis. Sci Rep. 2016;6:35214.
 Hamano I, Hatakeyama S, Iwamura H, Fujita N, Fukushi K, Narita T, et al. Preoperative chronic kidney disease predicts poor oncological outcomes after radical cystectomy in patients with muscle-invasive bladder cancer. Oncotarget. 2017;8:61404-14.
 Kodama H, Hatakeyama S, Fujita N, Iwamura H, Anan G, Fukushi K, et al. Preoperative chronic kidney disease predicts poor oncological outcomes after radical nephroureterectomy in patients with upper urinary tract urothelial carcinoma. Oncotarget. 2017;8:83183-94.
 Matsumoto A, Nakagawa T, Kanatani A, Ikeda M, Kawai T, Miyakawa J, et al. Preoperative chronic kidney disease is predictive of oncological outcome of radical cystectomy for bladder cancer. World J Urol. 2018;36:249-56.
 Hatakeyama S, Koie T, Narita T, Hosogoe S, Yamamoto H, Tobisawa Y, et al. Renal Function Outcomes and Risk Factors for Stage 3B Chronic Kidney Disease after Urinary Diversion in Patients with Muscle Invasive Bladder Cancer. PLoS One. 2016;11:e0149544.
 Yu HS, Hwang JE, Chung HS, Cho YH, Kim MS, Hwang EC, et al. Is preoperative chronic kidney disease status associated with oncologic outcomes in upper urinary tract urothelial carcinoma? a multicenter propensity score-matched analysis. Oncotarget. 2017.
 Rasool M, Ashraf MA, Malik A, Waquar S, Khan SA, Qazi MH, et al. Comparative study of extrapolative factors linked with oxidative injury and anti-inflammatory status in chronic kidney disease patients experiencing cardiovascular distress. PLoS One. 2017;12:e0171561.
 Chowdhury R, Peel NM, Krosch M, Hubbard RE. Frailty and chronic kidney disease: A systematic review. Arch Gerontol Geriatr. 2017;68:135-42.
 Sato T, Hatakeyama S, Okamoto T, Yamamoto H, Hosogoe S, Tobisawa Y, et al. Slow Gait Speed and Rapid Renal Function Decline Are Risk Factors for Postoperative Delirium after Urological Surgery. PLoS One. 2016;11:e0153961.
 Lu MS, Chen MF, Lin CC, Tseng YH, Huang YK, Liu HP, et al. Is chronic kidney disease an adverse factor in lung cancer clinical outcome? A propensity score matching study. Thorac Cancer. 2017;8:106-13.
 Na SY, Sung JY, Chang JH, Kim S, Lee HH, Park YH, et al. Chronic kidney disease in cancer patients: an independent predictor of cancer-specific mortality. Am J Nephrol. 2011;33:121-30.
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