Abstract Introduction CD8+ T cells are abundant in clear cell renal cell carcinoma (ccRCC) yet are often retained at the tumor margin, a hallmark of immune exclusion that limits immunotherapy efficacy. Tumor-associated macrophages (TAMs) may regulate this trafficking, but the specific myeloid subsets affecting post-extravasation T-cell migration remain poorly defined. Standard in vitro assays rarely capture the full sequence from T cell transendothelial migration to directional movement toward tumor and macrophage-mediated rejection, and these dynamics are hard to monitor in vivo. Improved in vitro models that are physiologically relevant, are needed to dissect macrophage control of T-cell homing in ccRCC. Methods To build a patient metadata-informed ccRCC microphysiological system (MPS),we performed the first ccRCC single-cell meta-analysis (>1 million cells) and applied Monocle3 pseudotime to define myeloid states and trajectories, identifying a transitional macrophage population. Guided by these insights, we engineered a T cell migration MPS consisting of a perfusable HUVEC-lined lumen in 3D collagen, primary ccRCC spheroids, ex vivo generated transitional macrophages, and CD8+ T cells. The platform quantifies CD8+ T-cell transendothelial and interstitial migration. Results Our myeloid meta-analysis identified an IL10/IL1B-high transitional state between monocytes and pro-inflammatory TAMs, upstream of all other immunosuppressive TAMs by pseudotime. We generated IL10/IL1B-high—like TAMs through tumor co-culture. When incorporated into the MPS, these TAMs reduced CD8+ T-cell extravasation and curtailed interstitial migration, suggesting differentiation towards TREM2+ immunosuppressive TAMs. Conclusion We defined and recreated a novel IL10/IL1B-high transitional state between monocytes and TAMs. Integrating meta-analysis with ex vivo MPS, we enable trajectory reconstruction from tumor-recruited monocytes toward immunosuppressive TAMs for mechanistic study and therapeutic targets discovery in ccRCC. Funding Source Carbone Cancer Center Cancer Center Support Grant NIH P30CA014520 Topic Categories Tumor Immunology: Cellular Responses and Tumor Microevironment (TIME)

Background: Statins are commonly used cholesterol-lowering drugs with evidence of additional chemoprotective and immunomodulatory effects resulting from the inhibition of DNA replication, cell proliferation, and TH1-cell inhibition. There are conflicting reports regarding the potential benefit of concurrent statin treatment on non-muscle invasive bladder cancer (NMIBC) and specifically on intravesical Bacillus Calmette-Guerin (BCG) outcomes. We therefore aimed to analyze the effects of concurrent BCG and statin use in patients with NMIBC. Methods: National Veterans Affairs databases were used to retrospectively identify men with NMIBC between 2000 and 2010 who were treated with BCG. Pharmacy data was interrogated, and patients were divided according to statin therapy status. Statins had to be given at the beginning of BCG treatments and continued for at least 6 months. Cox proportional hazard ratios after inverse propensity score-weighted and competing risks adjustments were calculated for recurrence, secondary events (e.g., progression), cancer-specific survival, and overall survival. Results: Among 8814 patients, with a median follow-up of 11.3 years, statins were used by 38% of the patients. Patients taking statins were older (71 vs. 68, p < 0.0001), had more comorbidities (Charlson Comorbidity Index (CCI > 2; 38.6% vs. 31.4%, p < 0.0001), and had a higher-grade disease (40.2% vs. 34.3%, p < 0.0001) compared to those not on statins. After adjusting for stage, grade, age, race, CCI, agent orange exposure, and year of diagnosis, Cox proportional hazard analysis revealed no association with recurrence (HR 1.05, 95% CI 0.97-1.15, p = 0.23), secondary events (HR 0.91, 95% CI 0.80-1.05, p = 0.189), or bladder cancer specific survival (HR 0.88, 95% CI 0.76-1.02, p = 0.09) of statin use. However, statins were associated with improved overall survival (HR 0.89, 95% CI 0.83-0.96, p = 0.002). Conclusions: Concurrent statin and BCG use in patients with NMIBC was associated with improved overall survival, but not recurrence, secondary events, or bladder cancer-specific survival. These results confirm the real-world well-established cardiovascular benefit of statin treatment and primary preventive care. However, this large population study did not find any association between statins and the outcomes of patients with NMIBC treated with BCG immunotherapy.

Neoadjuvant systemic treatment strategies have improved outcomes in several solid tumour types. This success has not yet been replicated in renal cell carcinoma (RCC). A consensus and international collaboration are urgently needed for the development of adaptive perioperative immunotherapy strategies for patients with RCC at high risk of recurrence.

Purpose: To evaluate safety and oncologic efficacy of percutaneous microwave ablation (MWA) for treating clinically localized T1b (cT1b) renal cell carcinoma (RCC). Methods: This single-center retrospective study was performed under a waiver of informed consent. Seventy-four consecutive patients (49M/25F) with 76 cT1b RCC (median tumor diameter 4.5 cm) were treated with percutaneous MWA between 5/2012 and 8/2020. Patients were stratified into two groups by technique, depending on whether antennas were repositioned for additional ablation or not. Primary efficacy, complications, and local tumor progression (LTP) were compared using the Wilcoxon rank sum and Fisher’s exact tests. The Kaplan Meier method was used for survival analysis. Results: Patients were elderly (median age 69.5), obese (median BMI 34.5) and comorbid (Charlson Comorbidity Index = 4). Most tumors were low-grade (grade 1-2) (67/89, 88%) and clear cell RCC was the most common histology (62/76, 82%). A median of three MWA antennas were powered at 65W for 7 min for treatment. Renal masses were larger (4.6 vs 4.5 cm, p=0.01) and procedure times longer (100 min vs 80.5 min, p=0.04) for the antenna reposition cohort (n=34, 45%). Primary efficacy and high-grade complication rates were 93% and 8%, respectively. The local tumor progression rate (LTP), at a median follow-up was 28.2 months, was 16%. Primary efficacy, low and high-grade complications, change in estimated glomerular filtration rate and LTP were similar between cohorts (p=0.20-0.55). Conclusion: Percutaneous MWA for cT1b RCC is safe in elderly and comorbid patients with acceptable oncologic efficacy. Repeat ablation is well-tolerated and can improve oncologic efficacy.

Purpose: This study aims to develop and validate a method for synthesizing 3D nephrographic phase images in CT urography (CTU) examinations using a diffusion model integrated with a Swin Transformer-based deep learning approach. Materials and Methods: This retrospective study was approved by the local Institutional Review Board. A dataset comprising 327 patients who underwent three-phase CTU (mean ± SD age, 63 ± 15 years; 174 males, 153 females) was curated for deep learning model development. The three phases for each patient were aligned with an affine registration algorithm. A custom deep learning model coined dsSNICT (diffusion model with a Swin transformer for synthetic nephrographic phase images in CT) was developed and implemented to synthesize the nephrographic images. Performance was assessed using Peak Signal-to-Noise Ratio (PSNR), Structural Similarity Index (SSIM), Mean Absolute Error (MAE), and Fréchet Video Distance (FVD). Qualitative evaluation by two fellowship-trained abdominal radiologists was performed. Results: The synthetic nephrographic images generated by our proposed approach achieved high PSNR (26.3 ± 4.4 dB), SSIM (0.84 ± 0.069), MAE (12.74 ± 5.22 HU), and FVD (1323). Two radiologists provided average scores of 3.5 for real images and 3.4 for synthetic images (P-value = 0.5) on a Likert scale of 1-5, indicating that our synthetic images closely resemble real images. Conclusion: The proposed approach effectively synthesizes high-quality 3D nephrographic phase images. This model can be used to reduce radiation dose in CTU by 33.3% without compromising image quality, which thereby enhances the safety and diagnostic utility of CT urography.

Introduction Metastatic renal cell carcinoma (mRCC) with sarcomatoid features is rare and historically associated with very poor outcomes. This study aimed to compare survival among patients with sarcomatoid RCC treated with either targeted therapy or immune checkpoint inhibitors (IO) and determine if the sequence of cytoreductive nephrectomy (CN) and systemic therapy was associated with survival. Methods Data from patients with mRCC who underwent CN at 7 institutions from 2006-2022 were analyzed. Patients were categorized into 4 cohorts by the type of systemic therapy they received and the sequence of treatments: upfront IO + deferred CN (IO+CN), upfront targeted therapy + deferred CN (targeted+CN), upfront CN + deferred IO (CN+IO), or upfront CN + deferred targeted therapy (CN+targeted). Cox regression evaluated variable associations with overall survival (OS). Results A total of 309/1421 (22%) mRCC patients treated with CN with sarcomatoid features in surgical pathology. Median age was 68, 29% were female, and most patients had clear cell RCC subtype (77%). The median follow-up was 37 months. Compared to a cohort of 1112 CN patients without sarcomatoid features, patients with sarcomatoid features had significantly shorter overall survival (median 15 vs 37 months, P<0.001).The treatment sequence was CN+targeted in 60%, CN + IO in 19%, targeted + CN in 14%, and IO+CN in 7%. Patients treated with IO therapy at any time had significantly improved OS compared to patients not treated with IO (median 40 vs 13 months, P=0.0001). Among patients receiving targeted therapy, upfront CN was associated with reduced mortality (HR 0.6 95%CI 0.4-0.9 P=0.03). However, among patients receiving IO therapy, the sequence of systemic therapy and CN was not associated with survival (P=0.7) (Figure). Conclusions Immune checkpoint inhibitors have significantly improved survival for patients with mRCC and sarcomatoid features treated with CN, regardless of the order in which the surgery was completed.

PURPOSE:Patients with metastatic renal cell carcinoma (mRCC) with oligometastatic disease can achieve radiographic disease-free (M1 NED) status after cytoreductive nephrectomy and concurrent complete metastasectomy. This study aimed to evaluate outcomes and identify risk factors associated with metastatic recurrence and overall survival in patients with mRCC M1 NED. MATERIALS AND METHODS:Patients with synchronous mRCC who were M1 NED after cytoreductive nephrectomy and concurrent complete metastasectomy from 4 institutions (2010-2020) were identified. Survival outcomes were analyzed by the Kaplan-Meier method. Patients were grouped by early (first year after surgery) recurrence or delayed/no known metastatic recurrence. Logistic regression modeling identified risk factors for first-year recurrence, and decision curve analysis evaluated the utility of a model incorporating identified risk factors. RESULTS:One hundred and nine M1 NED patients were identified including 36 patients who had recurrence in the first year after surgery and 73 patients with delayed or no recurrence. First-year recurrence resulted in significantly shorter overall survival compared with those with delayed/no recurrence after 1 year (median 15 vs 97 months, respectively, P < .0001). First-year recurrence predictors included liver metastases, increasing primary tumor size, and elevated preoperative C-reactive protein. A prognostic model incorporating these factors demonstrated discriminatory capacity and improved clinical decision-making compared with a universal immediate postoperative systemic therapy or active surveillance strategy. CONCLUSIONS:Liver metastasis, increasing primary tumor size, and elevated preoperative C-reactive protein are associated with increased risk for first-year progression after cytoreductive nephrectomy and complete metastasectomy. Despite radiographic NED status, high-risk patients should be considered for immediate systemic therapy after surgery given poor outcomes.

Introduction PSMA is expressed in the renal proximal tubule and by endothelial cells within the blood vessels of some tumors, including renal cell cancer (RCC). This study evaluated PSMA expression heterogeneity and prognostic association of PSMA expression in localized RCC using automated quantitative immunohistochemistry. Methods Tissue microarrays (TMAs) were created from non-metastatic clear cell RCC (ccRCC) patients, sampling 8 regions of each tumor and 3 samples from adjacent benign kidney tissue to determine PSMA expression. Two cohorts were evaluated: patients who progressed to metastatic disease and those who did not. Cohorts (progressed vs not progressed) were matched on age, gender, performance status, pT-stage, grade, and tumor size. PSMA expression was analyzed for associations with vascular endothelial cell density (CD31+ cells/mm2) and a previously published tumor-associated neovascularity index (CD105+/CD31+ ratio). Kernel density plots were used to demonstrate tissue heterogeneity. Results A total of 506 tissue samples were used to construct TMAs from 46 matched ccRCC patients in 2 cohorts: 26 patients developed metastatic progression with a median follow-up of 7 years (IQR 5-11), while 20 patients had no progression with a median follow-up of 11 years (IQR 8-15). Overall, the median tumor size was 9 cm.PSMA expression was highly heterogeneous throughout RCC tumors (Fig 1A, B). PSMA expression was higher in benign renal tissue than RCC and among tumors that did not progress (Fig 1C). PSMA was positively correlated with normal endothelial cell density (Spearman r = 0.32; P = 0.001) and negatively correlated with neovascularity (r = -0.29; P < 0.001). After multivariable analysis, higher PSMA expression was associated with improved progression-free survival (HR 0.46, P < 0.001) (Fig 1D). Conclusions PSMA expression demonstrates heterogeneity across tumor samples, in part reflecting endothelial cells and vascularity. PSMA was inversely correlated with tumor-associated neovascularity.In non-metastatic ccRCC, average tumor PSMA expression may be a positive prognostic marker for RCC, warranting further clinical investigation.

Introduction Transplanted patients who develop localized renal cell carcinoma (RCC) have a theoretically higher risk of disease progression because of pharmacologic immunosuppression. This study compared outcomes for localized RCC patients who received a prior organ transplant to a matched cohort of non-transplant patients. Methods Patients with tissue diagnosis of non-metastatic RCC after transplantation between 2000 and 2020 were identified from a solid organ transplant database. Transplanted patients were matched 1:2 to non-transplanted patients based on treatment type, age, grade, and tumor size. Clinical variables and survival outcomes were compared. Results A total of 81 patients were identified who developed non-metastatic RCC after organ transplant. The median age was 57 years, and 27% were female. Management strategies included surgery (65%), thermal ablation (23%), and active surveillance (10%). Among active surveillance patients, 0/9 developed metastases, and 4/9 died not due to RCC, with a median follow-up of 89 months. Papillary RCC was more common in the transplant than in matched cohorts (41 vs 18%, P<0.001).Among ablation patients, the median follow-up was 60 vs. 34 months for transplant vs. non-transplant patients (N=19, 43); P=0.002 (Figure 1A). No differences were found in 90-day complications, local recurrence, metastatic progression, or overall survival between transplant and non-transplant patients (P>0.05 for all) (Figure 2A).Among surgical patients, median follow-up was 65 vs 90 months for transplant vs. non-transplant patients (N=54, 104); P=0.08. Transplant patients were more likely to have postoperative complications (P=0.04) (Figure 1B). No difference was found in local recurrence, metastatic progression, or overall survival (P>0.05 for all) (Figure 2B)Among all patients, multivariable Cox regression showed that only the Charlson comorbidity index was significantly associated with mortality (HR 1.3, P<0.001) after adjusting for transplant status, age, grade, RCC subtype, and tumor size. Conclusions Patients who develop non-metastatic RCC after solid organ transplantation have similar outcomes as non-transplant patients. Mortality is primarily associated with comorbidity, and further studies should evaluate expanding the role of active surveillance for transplant patients with localized RCC.

Introduction Multiple prognostic models have been developed to help stratify patients with renal cell carcinoma (RCC) for the purposes of patient counseling and treatment selection. Utilization of histological features in these models, however, limits their application to the postoperative setting. A point of care (POC) urinalysis (UA) is a ubiquitous test in the field of urology and a standard part of the diagnostic workup for a renal mass in both the American Urological Association (AUA) and the European Association of Urology (EAU) guidelines. We sought to characterize the prevalence of abnormalities on preoperative UA among patients undergoing extirpative surgery for RCC, and whether presence of these factors impacts overall (OS) and cancer-specific survival (CSS). Methods Emory's prospectively maintained nephrectomy database was retrospectively reviewed for any stage, major histology (clear cell, chromophobe, papillary) RCC patients who underwent partial or radical nephrectomy from 2001-2022. Patient and pathologic characteristics were recorded for patients who had a UA within 90 days before surgery. Abnormal UA laboratory values were defined as specific gravity outside 1.005–1.030, ≥ +1 blood, and any protein, leukocyte esterase, glucose, or nitrites. Patients were categorized based on preoperative UA results: no abnormalities, 1 abnormality, and >1 abnormality. Primary outcomes of interest were OS and CSS. Kaplan-Meier curves and multivariable COX Hazards models were utilized to evaluate OS and CSS. Each UA component was assessed in individual multivariable models to determine specific associations with survival. Results A total of 1607 patients were evaluated: 644 (40.1%) had a normal UA, 508 (31.6%) had 1 abnormal UA component, and 455 (28.3%) had > 1 abnormal UA component. Univariable Kaplan Meier curves for ten-year OS and CSS based on the number of abnormalities on POC UA is shown in Figure 1. The presence of > 1 abnormal preoperative UA component was associated with worse OS (HR 1.67, p < 0.001) and CSS (HR 1.85, p < 0.001; Table 1). Blood (HR 1.34, p < 0.001), protein (HR 1.61, p < 0.001), and nitrites (HR 2.17, p = 0.002) were all independently associated with worse OS. Blood (HR 1.48, p = 0.002), protein (HR 1.49, p = 0.002), nitrites (HR 2.43, p = 0.012), and leukocyte esterase (HR 1.46, p = 0.009) were all independently associated with worse CSS. Conclusions A POC UA is easily accessible in the preoperative settings and adds little to no cost, with abnormalities associated with a higher risk of all-cause and cancer-specific mortality for patients with RCC undergoing nephrectomy. Specifically, abnormalities in blood, protein, nitrites, and leukocyte esterase were found to be independently associated with worse survival. Future research should examine whether resolution of UA abnormalities is associated with improved survival and investigate if the addition of UA abnormalities increases the prognostication of current models.

Predicting which patients will progress to metastatic disease after surgery for non-metastatic clear cell renal cell carcinoma (ccRCC) is difficult; however, recent data suggest that tumor immune cell infiltration could be used as a biomarker. We evaluated the quantity and type of immune cells infiltrating ccRCC tumors for associations with metastatic progression following attempted curative surgery. We quantified immune cell densities in the tumor microenvironment and validated our findings in two independent patient cohorts with multi-region sampling to investigate the impact of heterogeneity on prognostic accuracy. For non-metastatic ccRCC, increased CD8+ T cell infiltration was associated with a reduced likelihood of progression to metastatic disease. Interestingly, patients who progressed to metastatic disease also had increased percentages of exhausted CD8+ T cells. Finally, we evaluated the spatial heterogeneity of the immune infiltration and demonstrated that patients without metastatic progression had CD8+ T cells in closer proximity to ccRCC cells. These data strengthen the evidence for CD8+ T cell infiltration as a prognostic biomarker in non-metastatic ccRCC and demonstrate that multi-region sampling may be necessary to fully characterize immune infiltration within heterogeneous tumors. Tumor CD8+ T cell infiltration should be investigated as a biomarker in adjuvant systemic therapy clinical trials for high-risk non-metastatic RCC.

INTRODUCTION:The prevalence of preoperative paraneoplastic syndromes (PNS) in renal cell carcinoma (RCC) is poorly understood. Many laboratory abnormalities representative of PNS have demonstrated prognostic value when incorporated into predictive survival models in RCC. We sought to characterize the relationship between baseline prevalence of PNS with overall survival (OS) and cancer-specific survival (CSS) in RCC patients following nephrectomy. METHODS:Our prospectively maintained nephrectomy database was retrospectively reviewed for any stage, major histology RCC patients that underwent surgery from 2000 to 2022. Baseline laboratory values within 90 days (closest used) were required. Presence of PNS was defined according to established laboratory cutoffs. Kaplan-Meier curves estimated survival rates, and multivariable Cox proportional hazards models examined the association between PNS with OS and CSS following nephrectomy. RESULTS:2599 patients were included with listed staging: 1494 Stage I; 180 Stage II; 616 Stage III; 306 Stage IV. Proportion of patients presenting with >1 PNS significantly increased from stage I (31.3%) to stage IV (74.2%) RCC (P < .001). Elevated C-reactive protein was the most prevalent PNS (45.4%). On multivariable analysis, the presence of >1 PNS was associated with higher risk of all-cause (HR 2.09; P < .001) and cancer-specific mortality (HR 2.55; P < .001). The 10-year OS estimates as reported: 65.2% (no PNS), 52.3% (1 PNS), 36.6% (>1 PNS); and 10-year CSS estimates: 88.3% (no PNS), 79.3% (1 PNS), 61.6% (>1 PNS). DISCUSSION:Increased prevalence of PNS in major histology RCC was associated with a significant increase in the risk of all-cause and cancer-specific mortality even when accounting for patient and disease characteristics.

Purpose: To determine if microwave ablation (MWA) of retroperitoneal tumors can safely provide high rates of local tumor control. Materials and Methods: This retrospective study included 19 patients (median age, 65 years [range = 46-78 years]; 13 [68.4%] men and six [31.6%] women) with 29 retroperitoneal tumors treated over 22 MWA procedures. Hydrodissection (0.9% saline with 2% iohexol) was injected in 17 of 22 (77.3%) procedures to protect nontarget anatomy. The primary outcomes evaluated were local tumor progression (LTP) and complication rates. Oncologic outcomes, including overall survival (OS), progression -free survival (PFS), and treatment -free interval (TFI), were examined as secondary outcome measures. Results: Median follow-up was 18 months (range = 0.5-113). Hydrodissection was successful in displacing nontarget anatomy in 16 of 17 (94.1%) procedures. The LTP rate was 3.4% (one of 29; 95% CI: 0.1, 17.8) per tumor and 5.3% (one of 19; 95% CI: 0.1, 26.0) per patient. The overall complication rate per patient was 15.8% (three of 19), including two minor complications and one major complication. The OS rate at 1, 2, and 3 years was 81.8%, 81.8%, and 72.7%, respectively, with a median OS estimated at greater than 7 years. There was no evidence of a difference in OS (P = .34) and PFS (P = .56) between patients with renal cell carcinoma (six of 19 [31.6%]) versus other tumors (13 of 19 [68.4%]) and patients treated with no evidence of disease (15 of 22 [68.2%]) versus patients with residual tumors (seven of 22 [31.8%]). Median TFI was 18 months (range = 0.5-108). Conclusion: Treatment of retroperitoneal tumors with MWA combined with hydrodissection provided high rates of local control, prolonged systemic therapy-free intervals, and few serious complications.

Introduction Multiple treatment options are available for clinical T1 renal cell carcinoma (cT1 RCC) including surgery, thermal ablation, and active surveillance. Prior studies of cryoablation and radiofrequency ablation recommend ablation for tumors < 3cm. However, high powered microwave ablation (MWA) has fewer technical limitations and potentially enables larger more reliable ablation zones. The purpose of this study was to evaluate the effect of tumor diameter on oncologic outcomes for patients with clinically localized cT1 RCC treated with surgery or MWA. Methods A prospectively maintained database of patients with clinically localized RCC treated with either radical nephrectomy (RN), partial nephrectomy (PN), or MWA from 2000 to 2020 was utilized. Local recurrence-free (LRFS), metastasis-free (MFS), and cancer-specific survival (CSS) were estimated using the Kaplan-Meier method. Variables associated with survival were determined using Cox proportional hazard models (Table). Results 1209 patients were treated for cT1 RCC (353 MWA, 398 PN, 458 RN). Patients who underwent MWA were older (p<0.001) and had higher Charlson Comorbidity score (p<0.001). Median follow-up was 42 months (IQR 21-75).;Compared to surgery, MWA was associated with similar MFS and CSS when adjusting for age, histology, size, and grade (Table). MWA was, however, associated with an increased risk of local recurrence on multivariate analysis (HR 3.79, 95% CI 1.39-10.3). Of the 21 patients with local recurrence following MWA, 12 (57%) underwent repeat ablation (4 had surveillance, 4 had surgery, 1 had SBRT.)Stratified by size, RCC between 3.1-4 cm and 4.1-5 cm treated with MWA had no difference in LRFS compared to lesions < 3 cm treated with MWA (Figure). Lesions >5 cm treated with MWA had higher risk of local recurrence compared to lesions < 3 cm (HR 3.82, 95% CI 1.02, 14.3). Conclusions MWA effectively treats cT1 RCC with similar rates of metastatic progression and cancer specific survival compared to surgery. Local recurrence is more common with MWA, but recurrences can be salvaged by a second treatment. MWA effectively treats tumors up to 5 cm without compromising recurrence outcomes, which may suggest that the 3 cm size limit be re-evaluated with MWA.

Background The standard of care for patients with intermediate-to-high risk renal cell carcinoma is partial or radical nephrectomy followed by surveillance. We aimed to investigate use of nivolumab before nephrectomy followed by adjuvant nivolumab in patients with high-risk renal cell carcinoma to determine recurrence-free survival compared with surgery only. Methods In this open-label, randomised, phase 3 trial (PROSPER EA8143), patients were recruited from 183 community and academic sites across the USA and Canada. Eligible patients were aged 18 years or older with an Eastern Cooperative Oncology Group performance status of 0–1, with previously untreated clinical stage T2 or greater or Tany N+ renal cell carcinoma of clear cell or non-clear cell histology planned for partial or radical nephrectomy. Selected patients with oligometastatic disease, who were disease free at other disease sites within 12 weeks of surgery, were eligible for inclusion. We randomly assigned (1:1) patients using permuted blocks (block size of 4) within stratum (clinical TNM stage) to either nivolumab plus surgery, or surgery only followed by surveillance. In the nivolumab group, nivolumab 480 mg was administered before surgery, followed by nine adjuvant doses. The primary endpoint was investigator-reviewed recurrence-free survival in patients with renal cell carcinoma assessed in all randomly assigned patients regardless of histology. Safety was assessed in all randomly assigned patients who started the assigned protocol treatment. This trial is registered with ClinicalTrials.gov, NCT03055013, and is closed to accrual. Findings Between Feb 2, 2017, and June 2, 2021, 819 patients were randomly assigned to nivolumab plus surgery (404 [49%]) or surgery only (415 [51%]). 366 (91%) of 404 patients assigned to nivolumab plus surgery and 387 (93%) of 415 patients assigned to surgery only group started treatment. Median age was 61 years (IQR 53–69), 248 (30%) of 819 patients were female, 571 (70%) were male, 672 (88%) were White, and 77 (10%) were Hispanic or Latino. The Data and Safety Monitoring Committee stopped the trial at a planned interim analysis (March 25, 2022) because of futility. Median follow-up was 30·4 months (IQR 21·5–42·4) in the nivolumab group and 30·1 months (21·9–41·8) in the surgery only group. 381 (94%) of 404 patients in the nivolumab plus surgery group and 399 (96%) of 415 in the surgery only group had renal cell carcinoma and were included in the recurrence-free survival analysis. As of data cutoff (May 24, 2023), recurrence-free survival was not significantly different between nivolumab (125 [33%] of 381 had recurrence-free survival events) versus surgery only (133 [33%] of 399; hazard ratio 0·94 [95% CI 0·74–1·21]; one-sided p=0·32). The most common treatment-related grade 3–4 adverse events were elevated lipase (17 [5%] of 366 patients in the nivolumab plus surgery group vs none in the surgery only group), anaemia (seven [2%] vs nine [2%]), increased alanine aminotransferase (ten [3%] vs one [<1%]), abdominal pain (four [1%] vs six [2%]), and increased serum amylase (nine [2%] vs none). 177 (48%) patients in the nivolumab plus surgery group and 93 (24%) in the surgery only group had grade 3–5 adverse events due to any cause, the most common of which were anaemia (23 [6%] vs 19 [5%]), hypertension (27 [7%] vs nine [2%]), and elevated lipase (18 [5%] vs six [2%]). 48 (12%) of 404 patients in the nivolumab group and 40 (10%) of 415 in the surgery only group died, of which eight (2%) and three (1%), respectively, were determined to be treatment-related. Interpretation Perioperative nivolumab before nephrectomy followed by adjuvant nivolumab did not improve recurrence-free survival versus surgery only followed by surveillance in patients with high-risk renal cell carcinoma. Funding US National Institutes of Health National Cancer Institute and Bristol Myers Squibb.

You have accessJournal of UrologyHealth Services Research: Quality Improvement & Patient Safety II (MP33)1 May 2024MP33-03 "I WAS IN A VERY DEEP, DARK PLACE… I WASN'T PREPARED FOR THAT": A QUALITATIVE ANALYSIS OF THE MENTAL HEALTH NEEDS OF CYSTECTOMY PATIENTS Alexa Rose, Erica Zeng, Bhabna Pati, Megan Saucke, Taviah Levenson, E. Jason Abel, Tudor Borza, David F. Jarrard, Michael Risk, Daniel D. Shapiro, Esra Alagoz, and Kyle A. Richards Alexa RoseAlexa Rose , Erica ZengErica Zeng , Bhabna PatiBhabna Pati , Megan SauckeMegan Saucke , Taviah LevensonTaviah Levenson , E. Jason AbelE. Jason Abel , Tudor BorzaTudor Borza , David F. JarrardDavid F. Jarrard , Michael RiskMichael Risk , Daniel D. ShapiroDaniel D. Shapiro , Esra AlagozEsra Alagoz , and Kyle A. RichardsKyle A. Richards View All Author Informationhttps://doi.org/10.1097/01.JU.0001009520.30626.80.03AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Studies have shown that cystectomy has a large psychological and emotional burden on patients with bladder cancer. However, there has been little work characterizing potential areas of improvement. This project aimed to understand patients' experiences undergoing cystectomy and to identify patient-centric methods that improve perioperative support. METHODS: We conducted five focus groups (4 virtual, 1 in person) including patients with bladder cancer (n=17) who underwent cystectomy. Groups were divided by diversion type and gender. Patients were asked questions about their experiences and potential areas of improvement. The conversations were recorded and transcribed. Qualitative analysis was conducted using the "Sort and Sift, Think and Shift" method. Transcripts were coded in Nvivo and themes were summarized in higher level analysis. RESULTS: Throughout the discussion, patients reported that while their care team provided physical support for their illness, they did not provide information or discuss support for mental health during this challenging time. Patients described feelings of depression, anger, and anxiety in response to their cancer diagnosis, need for cystectomy, and living with urinary diversion. Many expressed a dichotomy in feeling grateful for the lifesaving surgery, while also feeling bitter about the impact cystectomy has had on their daily life. An overarching theme was the unexpected psychological burden of cystectomy. Patients experienced daily mental hardship while adapting to managing their urinary diversion. They experienced distress from diversion visibility in public and in sexual encounters. Patients did not bring up their mental health struggles with their surgeon, however, they reported that if their provider had initiated the discussion and offered a referral, they would have accepted support. Patients reported the benefit of social support networks for emotional support before and after surgery. CONCLUSIONS: Focus groups consistently identified the psychological difficulties of bladder cancer diagnosis and cystectomy. Patients identified potential avenues for improvement such as incorporating mental health support into the care plan and perioperative discussion regarding the potential emotional impact of surgery. Source of Funding: National Institute of Diabetes and Digestive and Kidney, NIH grant, T35DK062709. Wisconsin Urologic Research Institute © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e561 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Alexa Rose More articles by this author Erica Zeng More articles by this author Bhabna Pati More articles by this author Megan Saucke More articles by this author Taviah Levenson More articles by this author E. Jason Abel More articles by this author Tudor Borza More articles by this author David F. Jarrard More articles by this author Michael Risk More articles by this author Daniel D. Shapiro More articles by this author Esra Alagoz More articles by this author Kyle A. Richards More articles by this author Expand All Advertisement PDF downloadLoading ...

Introduction Benign uretero-enteric anastomotic strictures (UEAS) are a common and morbid long-term complication following cystectomy with urinary diversion. The incidence of benign UEAS in the literature varies from 3% up to 20%. The exact etiology of UEAS remains unclear but is likely multifactorial and secondary to locoregional ischemia and urine leakage at the uretero-enteric anastomosis resulting in fibrosis and scarring. In renal transplantation, one modifiable factor which has been shown to impact risk of vesico-ureteral stricture is ureteral length. Our objective in this study was to utilize a single-surgeon institutional database to identify risk factors for UEAS formation and determine if ureteral length impacted the risk of stricture formation. Methods A database of patients who underwent cystectomy with urinary diversion from 2015 to 2022 was analyzed. All cases were performed by a single surgeon to control variations in surgical technique. A “no-touch” technique was utilized for any ureteral manipulation. Distal ureteral resections were routinely sent for final pathology. The length of this resection was collected from pathology reports. Benign UIA strictures were confirmed with renal scintigraphy, antegrade nephrostogram, or endoscopic evaluation. Relationship between stricture formation and clinical parameters were assessed using T-tests, Chi-squared tests, and multivariable analysis. Results A total of 366 patients underwent cystectomy with urinary diversion from 2015 to 2022. Of the cohort, 35 (9.5%) patients developed UIA strictures. Median time to stricture formation was 12.5 months (IQR 4-30). Of the 711 ureteral anastomoses among the 366 patients, 40 anastomoses developed benign strictures (5.6%). Median distal ureteral length resected was significantly longer among anastomosis that did not form a stricture (2.3 cm vs 1.65 cm, p=0.044, Table 1). Strictures more commonly formed on the left side (65% vs 35%, p=0.051). Multivariable logistic regression adjusting for surgical approach, prior radiation, ureteral side, and urinary diversion type demonstrated longer distal ureteral resections were associated with a significantly lower risk of ipsilateral stricture formation (OR 0.73, 95% CI 0.58-0.92). Robotic surgical approach was associated with increased risk of UES formation (OR 2.30, 95% CI 1.14-4.72). Conclusions The etiology of benign UIA strictures is multifactorial. Vascular compromise is a critical hypothesis. We found that longer distal ureteral resections (and thus shorter ureters) were associated with a significantly lower risk of stricture formation in cystectomy patients, consistent with renal transplantation data. Limitations of this study include retrospective nature, limiting our ability to draw conclusions regarding unmeasured variables. Single-surgeon database limits widespread applicability, but does allow us to control for small, but potentially impactful, variation in technique.