Brant Inman

PURPOSE: Renal function outcomes between radical nephroureterectomy (RNU) and nephron-sparing surgery (NSS) for upper tract urothelial carcinoma (UTUC) patients are not well established. We sought to compare the incidence and factors associated with development of advanced chronic kidney disease (CKD) between RNU and NSS and examine the role of acute kidney injury (AKI) on renal function outcomes. METHODS: We retrospectively analyzed an institutional database for patients who underwent either RNU or NSS for UTUC. Cumulative incidence of postoperative advanced CKD, defined as eGFR < 30 ml/min/1.73 m2, was compared between groups. Fine-Gray competing risk regression was used to identify predictors of advanced CKD. Locally weight scatterplot smoothing was used to assess postoperative eGFR trends. AKI events were counted, staged, and assessed for influence of progression to advanced CKD. RESULTS: Four hundred and twenty-six patients were included in analysis, with a median follow up of 6.68 years (IQR 3.4-12.2). Median preoperative eGFR was similar between the groups (NSS: 68 ml/min/1.73 m2, RNU: 65 ml/min/1.73 m2,P = 0.220). Cumulative incidence of advanced CKD was significantly lower in the NSS cohort (P = 0.009). Factors associated with advanced CKD included age, diabetes, recurrent AKI and RNU. Percent of patients with an AKI event differed between the groups (51.5% NSS, 72.7% RNU, P = <0.001), there was no between group difference in percentage of patients with recurrent AKI (25.6% NSS, 25.9% RNU, P =1). CONCLUSION: NSS provides a renal function benefit in UTUC. AKI is common among UTUC patients and recurrent AKI is a risk factor for development of advanced CKD.

Immune checkpoint inhibitors (ICI) have revolutionized the care of urologic malignancies, in particular urothelial carcinoma (UC) and renal cell carcinoma (RCC). Five PD-1/PD-L1 ICIs have been approved for platinum-refractory advanced UC: atezolizumab, pembrolizumab, nivolumab, durvalumab, and avelumab. Atezolizumab and pembrolizumab have also been approved for cisplatin-ineligible advanced UC. For advanced RCC, nivolumab was the first ICI approved in the setting of prior antiangiogenic therapy. The ICI combination of nivolumab with ipilimumab has recently demonstrated improved overall response rate and overall survival in intermediate- and poor-risk patients with treatment-naïve, clear cell metastatic RCC (mRCC) and has become the standard of care. An ICI and vascular endothelial growth factor (VEGF)-targeted therapy combination, atezolizumab and bevacizumab, was randomized against sunitinib in the first-line treatment of mRCC, and this trial recently reported improvement of progression-free survival with the combination in a subset of patients. More ICI-ICI and ICI-VEGF inhibitor combinations are in clinical testing. The development of ICIs in prostate cancer has been challenging, and no ICIs are currently approved; however, progress is being made.