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Survival of Patients with Chronic Kidney Disease Treated with Radical Cystectomy and Risk Factors of Glomerular Filtration Rate Loss Following RC: Two Systematic Reviews and Meta-Analyses of Interplay between RC and Renal Function - Beyond the Abstract

Radical cystectomy (RC) with urinary diversion is considered the standard treatment for patients with muscle-invasive and select high-risk non-invasive urothelial bladder cancer (BCa).1 However, this complex urological procedure is associated with a significant rate of short- and long-term postoperative complications.2 Additionally, up to 25% of patients undergoing RC may present with preoperative chronic kidney disease (CKD).3 On the other hand, RC and/or urinary diversion itself may compromise kidney function (i.e., estimated glomerular filtration rate (eGFR) decline).4 Despite surgical advancements and new technologies, there has been no overall improvement in recurrence-free survival following RC in the past two decades.1-3 Both pre- and postoperative CKD have been shown to affect long-term outcomes of BCa patients after RC.



Understanding the Evidence: Literature Search and Inclusion Criteria

Two systematic reviews and meta-analyses were conducted to comprehensively evaluate the potential risk factors of CKD in BCa patients undergoing RC and assess overall and oncological survival rates in patients with CKD who underwent RC. The studies were identified through a literature search performed in various databases, and the systematic reviews were conducted following the Preferred Reporting Items for Systematic Review and Meta-analyses (PRISMA) guidelines.



Factors Associated with GFR Decline after RC

The first meta-analysis, including 10 studies (15,502 patients), focused on potential risk factors of significant eGFR decline (defined as ≥10%) and/or any CKD upstage in BCa patients who received RC with urinary diversion. Several factors were found to be associated with an increased risk of GFR decline:

A. Preoperative factors: Advanced age was associated with an increased risk of eGFR decline (HR 1.03 per year), especially in patients with pre-RC CKD2. In addition, lower baseline renal function was associated with an increased risk of eGFR decline (HR 1.2), particularly in patients with pre-RC CKD3a and CKD2. Finally, patients' comorbidities, such as higher Charlson Comorbidity Index (CCI) (HR 1.5), hypertension (HTN) (HR 1.2), and diabetes mellitus (DM) (HR 1.3) were significantly associated with a higher risk of eGFR decline.

B. Postoperative factors: The presence of postoperative uretero-enteric stricture (HR 1.9) and hydronephrosis (HR 1.7) were associated with an increased risk of eGFR decline.

Nevertheless, factors such as sex, preoperative hydronephrosis, perioperative chemotherapy, and diversion type (continent vs. incontinent) were not found to be significant risk factors for eGFR decline.


Impact of CKD on Survival Outcomes

The second meta-analysis, including seven studies (6900 patients), aimed to evaluate the impact of pre-RC CKD on overall survival (OS), cancer-specific survival (CSS), and metastasis-free survival (MFS) in BCa patients undergoing RC. The results revealed that patients with higher preoperative CKD stages had worse survival outcomes. First, we found that patients with higher CKD stages had reduced OS, with a 47% increased risk of overall mortality compared to those with a normal kidney function (i.e., higher eGFR). Second, higher CKD stages were associated with a 109% increase in the risk of cancer-specific mortality. Lastly, patients with higher CKD stages had a 54% increased risk of metastasis. These findings were especially pronounced in patients with CKD3 and CKD3b, highlighting the significance of preoperative renal function as a prognostic indicator of long-term outcomes following RC.
Conclusion and Implications

The results of these systematic reviews and meta-analyses have shed light on the risk factors associated with long-term eGFR decline after RC and the impact of pre-RC CKD on survival outcomes in BCa patients. Age, baseline renal function, comorbidities (CCI, HTN, DM), as well as postoperative hydronephrosis, and uretero-enteric stricture were identified as significant risk factors for eGFR decline following RC. In contrast, factors such as sex, preoperative hydronephrosis, perioperative chemotherapy, and diversion type did not significantly impact GFR decline. Furthermore, preoperative CKD was found to be a critical predictor of overall and oncological survival in patients undergoing RC. Patients with higher CKD stages had worse survival outcomes compared to those with higher eGFR.

This information presented in this study is valuable for physicians in preoperative counseling and shared decision-making of patients suffering from BCa. Identifying and managing modifiable risk factors of CKD could potentially help improve patient outcomes and quality of life after RC. However, the results of this study should be interpreted cautiously given some limitations, including the observational nature of included studies which could be associated with a heterogeneity of population, design, and outcomes.

Written by: Reza Sari Motlagh, MD, FEBU,1 Alireza Ghoreifi, MD,2 Hooman Djaladat, MD,3 & Shahrokh F Shariat, MD1

  1. Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria
  2. Institute of Urology, Keck School of Medicine, University of Southern California, Los Angeles, CA
  3. Dean’s Professor of Clinical Urology, Department of Urology, Norris Cancer Center, USC
References:

  1. Witjes JA, Bruins HM, Cathomas R, Compérat EM, Cowan NC, Gakis G, et al. European Association of Urology Guidelines on Muscle-invasive and Metastatic Bladder Cancer: Summary of the 2020 Guidelines. Eur Urol 2021;79:82–104.
  2. Mitra AP, Cai J, Miranda G, Bhanvadia S, Quinn DI, Schuckman AK, et al. Management Trends and Outcomes of Patients Undergoing Radical Cystectomy for Urothelial Carcinoma of the Bladder: Evolution of the University of Southern California Experience over 3,347 Cases. J Urol 2022;207:302-313.
  3. 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.
  4. Schmidt B, Velaer KN, Thomas I-C, Ganesan C, Song S, Pao AC, et al. Renal Morbidity Following Radical Cystectomy in Patients with Bladder Cancer. Eur Urol Open Sci 2022;35:29–36.
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