Study Type – Diagnosis (exploratory cohort) Level of Evidence 2b What’s known on the subject? and What does the study add? For over 30 years it has been recognized that there is an association between end‐stage renal disease (ESRD) and the development of malignancy, particularly renal cortical tumour. Observational studies have consistently shown that patients with severely decreased glomerular filtration rate (GFR) develop cancer more frequently than their age‐ and exposure‐matched controls. This study is the first of its kind to look directly at the relationship between GFR and tumour size, in an effort to begin to examine the relationship between kidney function and oncogenesis. OBJECTIVE • To examine the relationship between tumour diameter and estimated GFR (eGFR) in patients with renal cell carcinoma (RCC). PATIENTS AND METHODS • In total, 1009 patients undergoing partial or radical nephrectomy for unilateral RCC were identified in the Columbia Urologic Database. • eGFR was calculated using the modification of diet in renal disease equation using demographic data and preoperative serum creatinine values. • Data on patient demographics, tumour characteristics, and comorbidities were analyzed using univariate and multivariate regression analysis. RESULTS • Mean ( sd , range) tumour diameter was 5.29 (3.8, 0.3–29) cm. Mean ( sd , range) eGFR was 75 (23.4, 3–173) mL/min per 1.73 m 2 . • In multivariate regression analysis, tumour diameter independently predicted decreased preoperative eGFR (coefficient, −0.513; P = 0.008) when controlling for hypertension and race. • Consistent with this, decreased preoperative eGFR independently predicted increased tumour diameter (coefficient, −0.013; P = 0.007) when controlling for race, histology and smoking status. CONCLUSION • Tumour diameter and decreased preoperative eGFR are independently correlated in patients with RCC.
Background: Immune checkpoint inhibitors (ICIs) have become the mainstay treatment of metastatic kidney cancer, demonstrating enhanced outcomes and durable responses in select patient subgroups. However, identifying reliable prognostic biomarkers for treatment outcomes remains challenging. Objectives: This study aimed to assess the correlation between baseline inflammatory markers and overall survival (OS), progression-free survival (PFS), and clinical benefit (CB) in metastatic kidney cancer patients receiving ICIs. CB was defined as patients achieving stable disease, partial response, or complete response. Design: Retrospective, single-center study. Methods: A retrospective analysis was conducted on 401 adult patients with advanced kidney cancer treated with ICIs at Emory Winship Cancer Institute between 2018 and 2023. Modified Glasgow Prognostic Score (mGPS), neutrophil-to-lymphocyte (NLR), monocyte-to-lymphocyte (MLR), platelet-to-lymphocyte (PLR), and neutrophil-to-eosinophil ratios (NER) were collected from baseline blood samples. Results: Among 401 patients (median age, 66; 71% male; 21% Black/African American), median follow-up was 43.0 months (95% CI, 36.6–51.4). Patients with mGPS scores of 0 had longer OS than those with a score of 1 (hazard ratio (HR), 0.38; 95% CI, 0.23–0.62; p < 0.001) and 2 (HR, 0.37; 95% CI, 0.20–0.67; p = 0.001), and longer PFS compared to patients with mGPS scores of 1 (HR, 0.66; 95% CI, 0.44–0.98; p = 0.039) and 2 (HR, 0.44; 95% CI, 0.29–0.67; p < 0.001). Low baseline NLR was associated with longer PFS (HR, 0.73; 95% CI, 0.54–0.97; p = 0.032). Low baseline MLR correlated with improved OS (HR, 0.60; 95% CI, 0.44–0.83; p = 0.002) and PFS (HR, 0.73; 95% CI, 0.55–0.97; p = 0.031). Similarly, low baseline PLR was associated with higher CB likelihood (odds ratio (OR), 2.20; 95% CI, 1.31–3.69; p = 0.003), and low baseline NER was linked to improved OS (HR, 0.63; 95% CI, 0.46–0.87; p = 0.004), PFS (HR, 0.67; 95% CI, 0.51–0.88; p = 0.003), and higher CB (OR, 2.04; 95% CI, 1.20–3.46; p = 0.008). Conclusion: Lower levels of systemic inflammatory markers are associated with more favorable clinical outcomes with ICI treatment. Prospective studies are needed for further validation.
512 Background: Non-clear cell renal cell carcinoma (nccRCC) includes several molecularly distinct subtypes of renal carcinoma. Due to their rarity, nccRCC subtypes have been understudied, and treatment options are often adapted from clear cell RCC therapies. Trials investigating immune checkpoint inhibitors (ICIs) have demonstrated promising efficacy and survival benefits in certain nccRCC histologies. This report aims to present our experience with nccRCC, focusing on patient characteristics, treatment choices, and survival outcomes in the era of ICIs. Methods: A retrospective analysis was conducted on adult patients with metastatic RCC treated at the Emory Winship Cancer Institute between 2018 and 2024. nccRCC histologies were identified and confirmed through pathology reports. An objective response is defined as a complete or partial response by RECIST v1.1. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method with SAS 9.4 software to calculate survival probabilities. Results: We identified 69 patients with various nccRCC histologies, with papillary RCC (pRCC) being the most common (36.2%), followed by unclassified RCC (24.6%). The median age was 63 years. 59.4 of the patients were male, and 75.4% of the patients had an ECOG PS of 0 or 1. 53.6% of the patients were White, while 40.6% were African American or Black. Nephrectomy was performed in 44 patients (63.8%). The median follow-up time was 24 months. ICI-based treatments were used as the first-line option in 52% of patients, with 88% of unclassified RCC patients receiving ICI-based regimens as first-line. The mOS was longest in patients with chromophobe RCC at 21 months (4, NA), followed by patients with unclassified RCC at 19 months (6, NA). Among pRCC patients, there was no significant difference in mOS between African American or Black patients (12 months) and White patients (10.5 months; p=0.61). mOS was similar across ICI monotherapy, dual ICI therapy, and ICI+TKI combinations. 12-month survival rates were 50%, 57%, and 33% (p=0.21), and objective response rates (ORR) were 11%, 14%, and 11% for ICI monotherapy, dual ICI, and ICI+TKI combinations, respectively. Conclusions: Our study highlights the heterogeneity of non-clear cell RCC subtypes. The rare nature of nccRCC and the small patient cohort in our study limited its statistical power, emphasizing the importance of larger studies and expanded clinical trials to better understand and optimize treatment strategies for this understudied group of renal carcinomas. Histology n White African American or Black 12 Months OS Rate 12 Months PFS Rate ORR Papillary 25 12 12 46% (25, 64) 44% (7, 78) 12% Unclassified 17 10 6 63% (35, 81) 43% (10, 73) 35% Translocation 9 4 3 67% (21, 91) 36% (17, 56) 0% Collecting Duct 7 4 3 43% (10, 73) 0% (NA) 14% Chromophobe 6 6 - 67% (20, 90) 34% (12, 58) 0%
Pressurized saline irrigation is commonly used during ureteroscopy, which can cause an increase in intrarenal pressure leading to postoperative pain, sepsis, and renal injury due to pyelovenous and pyelolymphatic backflow. To prevent retrograde stone migration during ureteroscopic lithotripsy, antiretropulsion devices can be deployed, which may or may not protect the kidney against high intrarenal pressures. This study compares the intrarenal pressures generated during the use of two antiretropulsion devices in an ex vivo porcine model.Using an ex vivo porcine model of the urinary system, flexible ureteroscopy was performed at the proximal, mid, and distal ureter. Intrarenal pressures were measured in the absence and presence of a coil-based antiretropulsion device and a multifold film-based device. Intrarenal pressure measurements were obtained while using saline irrigation at a gravity of 84 cm H(2)O and pressures of 150 and 300 mm Hg.The deployment of a coil device resulted in a significant increase in intrarenal pressures during ureteroscopy with pressurized irrigation when compared with intrarenal pressures without a device. The use of a multifold film device that occluded the ureter during ureteroscopy resulted in a decrease in intrarenal pressures at an irrigation pressure of 300 mm Hg when compared with pressures without a device. In the remaining configurations, the intrarenal pressures were only minimally elevated. When comparing the two devices to each other, the multifold film device had significantly lower intrarenal pressures at each configuration. This has potential implications in preventing renal injury and/or sepsis during ureteroscopy.The use of a multifold film antiretropulsion device during ureteroscopy with high-pressure irrigation can potentially protect the kidney from elevated intrarenal pressures.
A major advance in the standard practice of tissue-based pathology is the new discipline of systems pathology (SP) that uses computational modeling to combine clinical, pathologic, and molecular measurements to predict biologic activity. Recently, a SP-based prostate cancer (PCa) predictive model for both preoperative (Px+) and postoperative (Px) prostatectomy has been developed. The purpose of this study is to calculate the percent agreement and the concordance between the Px+ and Px end points.Fifty-three patients underwent robot-assisted prostatectomy for PCa, and had Px+ and Px testing performed. Data were collected on Px+ end points and Px end points along with pathologic specimen results. The percent agreement and the degree of correlation between the Px+ and Px end points were then calculated.The percent agreement (PA) between Px+ end points and Px end points ranged from 77% to 87%. The PA between a high Px+ favorable pathology (FP) classification and dominant Gleason score ≤ 3 and Gleason sum ≤ 6 was 71.7% and 37.4%, respectively. On univariate analysis, Px+ disease progression (DP) score significantly correlated with Px prostate-specific antigen recurrence (PSAR) score (P<0.001), while Px+ DP probability significantly correlated with PxPSAR probability (P<0.001). Px+ FP probability significantly correlated with postprostatectomy dominant Gleason grade ≤ 3 (P<0.001) and Gleason sum (P<0.001).The PA between Px+ and Px testing end points for radical prostatectomy patients was very good. Furthermore, there was a direct correlation between most Px+ and Px end points. While the Px+FP classification and Gleason sum demonstrated a poor PA, Px+FP score still maintained a direct correlation to prostatectomy Gleason sum.
603 Background: Multiple studies on various cancer types have investigated concomitant statin, aspirin, and metformin use with immune checkpoint inhibitors. While some found improved OS and PFS, others reported no significant effect. In RCC, a retrospective study linked statins with improved OS and PFS. We aimed to evaluate the impact of statin, aspirin, and metformin use on survival in RCC patients treated with ICIs. Methods: A retrospective analysis was conducted on adult patients with advanced RCC treated with ICIs at Emory Winship Cancer Institute between 2018 and 2024. Concomitant medication use was assessed via chart review during active ICI treatment. Clinical benefit (CB) is determined by stable disease, partial response, and complete response. The multivariate analysis model for statin was built by controlling the age, gender, race, smoking status, IMDC risk group, ECOG PS, clear cell histology, prior treatments, and liver metastases. Variables were subject to backward elimination at the significant level of p < 0.2. Results: Data from 400 patients were analyzed, with a median follow-up of 43.0 months (95% CI: 36.6-51.4). Of 400 patients, 138 (34.5%) were treated with ICI monotherapy, 131 (32.8%) treated with dual ICI combination, and 114 (28.5%) were treated with ICI and TKI combinations. 85 (21.3%) of the patients were African American or Black, 284 (71%) of them were White, and 239 (59.8%) were treated with ICIs as first-line. Statin use was more common among patients without prior treatment, without liver metastasis, older individuals, and those with a BMI ≥24.9. In univariate analysis, statin use showed potential associations with longer OS (HR 0.82; 95% CI 0.62-1.07 p=0.144), longer PFS (HR 0.81; 95% CI 0.64-1.02 p=0.071), and a higher likelihood of receiving CB (OR 1.85; 95% CI 1.17-2.92 p=0.008). However, multivariate analysis did not confirm significant differences in survival or CB. Survival outcomes are summarized in the table. Conclusions: Our analysis found no significant impact of concomitant statin, aspirin, or metformin use on RCC patient outcomes treated with ICIs. Further advancements in our understanding of tumor biology and checkpoint inhibitors might explain how concomitant medication affects treatment outcomes. Our study is limited by its retrospective design, and future prospective trials are necessary to provide definitive evidence. Univariate analysis of survival outcomes and clinical benefit. Overall Survival Progression-free survival Clinical Benefit HR (95% CI) p-value HR (95% CI) p-value OR (95% CI) p-value Statin Y n=170 0.82 (0.62-1.07) 0.144 0.81 (0.64-1.02) 0.071 1.85 (1.17-2.92) 0.008 Statin N n=230 - - - - - - Aspirin Y n=138 0.93 (0.70-1.24) 0.623 0.84 (0.66-1.07) 0.159 1.49 (0.93-2.40) 0.100 Aspirin N n=262 - - - - - - Metformin Y n=49 1.04 (0.68-1.57) 0.860 0.80 (0.55-1.15) 0.231 1.37 (0.68-2.78) 0.379 Metformin N n=351 - - - - -
