The Impact of Preoperative Severe Renal Insufficiency on Poor Postsurgical Oncological Prognosis in Patients with Urothelial Carcinoma - Beyond the Abstract

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 [13]. 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


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