SMARCB1 regulates the hypoxic stress response in sickle cell trait.

Renal medullary carcinoma (RMC) is an aggressive kidney cancer that almost exclusively develops in individuals with sickle cell trait (SCT) and is always characterized by loss of the tumor suppressor SMARCB1. Because renal ischemia induced by red blood cell sickling exacerbates chronic renal medullary hypoxia in vivo, we investigated whether the loss of SMARCB1 confers a survival advantage under the setting of SCT. Hypoxic stress, which naturally occurs within the renal medulla, is elevated under the setting of SCT. Our findings showed that hypoxia-induced SMARCB1 degradation protected renal cells from hypoxic stress. SMARCB1 wild-type renal tumors exhibited lower levels of SMARCB1 and more aggressive growth in mice harboring the SCT mutation in human hemoglobin A (HbA) than in control mice harboring wild-type human HbA. Consistent with established clinical observations, SMARCB1-null renal tumors were refractory to hypoxia-inducing therapeutic inhibition of angiogenesis. Further, reconstitution of SMARCB1 restored renal tumor sensitivity to hypoxic stress in vitro and in vivo. Together, our results demonstrate a physiological role for SMARCB1 degradation in response to hypoxic stress, connect the renal medullary hypoxia induced by SCT with an increased risk of SMARCB1-negative RMC, and shed light into the mechanisms mediating the resistance of SMARCB1-null renal tumors against angiogenesis inhibition therapies.

Freehand versus Grid-Based Transperineal Prostate Biopsy: A Comparison of Anatomical Region Yield and Complications.

PURPOSE: The freehand (FH) technique of transperineal prostate biopsy using commercialized needle access systems facilitates a reduction in anesthesia requirements from general to local or local/sedation. We sought to compare the efficacy and complication rates of the FH method with those of the standard grid-based (GB) method. MATERIALS AND METHODS: The GB method was performed from 2014 to 2018, and the updated FH technique was performed from 2018 to 2020, yielding comparative cohorts of 174 and 304, respectively. RESULTS: The FH and GB techniques demonstrated equivalent yields of ≥Gleason grade group (GGG)-2 prostate cancer (PCa). The FH group had a significantly higher mean number of cores with ≥GGG-2 PCa involvement (p=0.011) but a significantly lower mean number of biopsy samples (p <0.01). The urinary retention rate of the GB group (10%) was significantly higher than that of the FH group (1%; p <0.01). The rates of ≥GGG-2 PCa involvement in the anterior (GB, 31%) and anteromedial (FH, 22%) sectors were higher than those in other sectors (range, 0%-9%). For multiparametric magnetic resonance imaging, the rate of ≥GGG-2 PCa detection in the anteromedial prostate (23%) was nearly half that in other locations (range, 38%-55%). CONCLUSIONS: Compared with GB transperineal biopsy, FH transperineal biopsy demonstrates an equivalent cancer yield with no risk of sepsis, a significantly reduced risk of urinary retention, and reduced anesthesia needs. The higher number of cores with ≥GGG-2 PCa involvement in the FH group suggests that FH transperineal biopsy can sample the prostate better than GB-transperineal biopsy can.

Comparing confirmatory biopsy outcomes between MRI-targeted biopsy and standard systematic biopsy among men being enrolled in prostate cancer active surveillance.

OBJECTIVES: To evaluate the ability of magnetic resonance imaging (MRI)-targeted biopsy combined with systematic biopsy (MRI-biopsy) to reduce negative biopsies and detect clinically significant prostate cancer compared to systematic biopsy (SB) alone in the confirmatory biopsy setting using matched cohorts. PATIENTS AND METHODS: Patients were identified from an active surveillance database who had a previously positive transrectal ultrasonography-guided SB followed by a confirmatory biopsy at a single institution between 2006 and 2019. Patients were divided into two cohorts based on confirmatory biopsy technique: SB alone or MRI-biopsy (which included MRI-targeted and systematic biopsies). Cohorts were then matched on age, prostate-specific antigen (PSA) level, number of positive cores on initial biopsy and initial biopsy Gleason grade group (GG). Logistic regression was performed to identify associations with confirmatory biopsy upgrading. RESULTS: After matching, 514 patients were identified (257 per cohort). PSA, prostate volume and PSA density prior to initial biopsy, in addition to total number of initial biopsy positive cores and GG, were similar between the matched cohorts. After confirmatory biopsy, 118/257 patients (45.9%) in the MRI-biopsy cohort were upgraded compared to 46/257 patients (17.9%) in the SB cohort (P < 0.001). The rate of negative confirmatory biopsy was 32/257 (12.5%) compared to 97/257 (37.7%) in the MRI-biopsy and SB cohorts, respectively (P < 0.001). Confirmatory MRI-biopsy was associated with greater odds of confirmatory biopsy upgrade from GG 1 to ≥GG 2 compared to SB alone (odds ratio 3.62, 95% confidence interval 1.97-6.63; P < 0.001). CONCLUSION: The addition of MRI-targeted biopsies to SB in the confirmatory biopsy setting among men with previously detected prostate cancer resulted in fewer negative confirmatory biopsies and detection of more clinically significant prostate cancer compared to SB alone.

Survival following cytoreductive nephrectomy: a comparison of existing prognostic models.

OBJECTIVE: To validate models currently used to predict metastatic renal cell carcinoma (mRCC) outcomes in a cohort of patients undergoing cytoreductive nephrectomy (CN). PATIENTS AND METHODS: A total of 10 RCC prognostic models (International Metastatic RCC Database Consortium [IMDC]; Memorial Sloan Kettering Cancer Center [MSKCC]; Culp; Leibovich; University of California at Los Angeles Integrated Staging System [UISS]; Stage, Size, Grade, and Necrosis [SSIGN]; Yaycioglu; Karakiewicz; Cindolo; and Margulis) were chosen based on clinical relevance and use in clinical trial design. Model validation was performed using patients who underwent CN at a single institution between 2005 and 2017, and model discrimination (ability to select patients at risk of death) was assessed. Concordance indices (c-index) were calculated and compared with originally published c-indices. RESULTS: A total of 515 CN patients were stratified according to the prognostic models. A total of 387 (75%) died over the study period, with estimated 3-year survival of 46.1% (95% confidence interval [CI] 41.6-50.4%). All models' discriminatory capacity underperformed when compared to the originally published c-indices. The c-indices ranged from 0.53 (95% CI 0.50-0.56) for the Cindolo model to 0.61 (95% CI 0.58-0.64) for the Leibovich model. The MSKCC and IMDC models performed poorly with c-indices of 0.55 and 0.56, respectively. CONCLUSION: Currently used prognostic models have limited discriminatory capacity when applied to a modern cohort of patients undergoing CN. They are inadequate for risk stratification and randomisation in prospective clinical trials of untreated patients with mRCC. Caution should be used when using these models for clinical decision making.

Patient selection for cytoreductive nephrectomy in combination with targeted therapies or immune checkpoint inhibitors.

PURPOSE OF REVIEW: Recent cytoreductive nephrectomy studies provide continued evidence of the critical role of patient selection prior to surgery. The purpose of this review is to examine current data regarding patient selection for cytoreductive surgery and evaluate, which metastatic renal cell carcinoma (mRCC) patients are likely to benefit from surgical treatment. RECENT FINDINGS: Individual prognostic factors and risk stratification models can be used to estimate survival for mRCC patients and to aid in patient selection. Recent studies also have demonstrated prognostic value for serum labs or tumor histology.The available data suggests that upfront cytoreductive nephrectomy is associated with benefit for selected mRCC patients with good performance status and favorable or intermediate-risk criteria. Upfront systemic therapy should be considered for patients with poor-risk features and poor surgical candidates after multidisciplinary discussion with surgical and medical oncology teams. SUMMARY: Ideal patient selection for cytoreductive nephrectomy should include individual consideration of poor prognostic risk factors and discussion of the potential risks and benefits for surgery.

Shorter Ureters Lead to Fewer Strictures Following Cystectomy and Urinary Diversion.

OBJECTIVE: To identify the impact of length of distal ureteral resection on the risk of benign uretero-enteric anastomotic stricture (UEAS) formation following cystectomy and urinary diversion. METHODS: A database of patients who underwent cystectomy and urinary diversion from 2015 to 2022 was analyzed. Distal ureteral resections were sent for final pathology. The length of resected ureter was collected from pathology reports. Benign UEAS were confirmed with renal scintigraphy, antegrade nephrostogram, or endoscopic evaluation. The relationship between stricture formation and clinical parameters were assessed using T-tests, chi-square tests, and multivariable analysis. RESULTS: A total of 366 patients underwent cystectomy and urinary diversion. Of the cohort, 35 (9.5%) patients developed UEAS. Median time to stricture formation was 12.5months (IQR 4-30). Of the 711 uretero-enteric anastomoses, 40 (5.6%) ultimately formed a UEAS. Median distal ureteral resection was significantly longer among ureteral anastomoses which did not form a UEAS (2.3 cm vs 1.65 cm, P = .028). Multivariable logistic regression adjusting for surgical approach, prior radiation, ureteral side, and urinary diversion type demonstrated that longer distal ureteral resections were inversely associated with odds of UEAS formation (OR 0.73, 95% CI 0.58-0.92). Multivariable Cox regression analysis similarly showed that length of distal ureteral resection was inversely associated with time to stricture formation (HR 0.78, 95% CI 0.62-0.98). CONCLUSION: 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.

The Selection for Cytoreductive Nephrectomy (SCREEN) Score: Improving Surgical Risk Stratification by Integrating Common Radiographic Features.

BACKGROUND: Careful patient selection is critical when considering cytoreductive nephrectomy (CN) for metastatic renal cell carcinoma (mRCC) but few studies have investigated the prognostic value of radiologic features that measure tumor burden. OBJECTIVE: To develop a prognostic model to improve CN selection with integration of common radiologic features with known prognostic factors associated with mortality in the first year following surgery. DESIGN, SETTINGS, AND PARTICIPANTS: Data were analyzed for consecutive patients with mRCC treated with upfront CN at five institutions from 2006 to 2017. Univariable and multivariable models were used to evaluate radiographic features and known risk factors for associations with overall survival. Relevant factors were used to create the SCREEN model and compared to the International mRCC Database Consortium (IMDC) model for predictive accuracy and clinical usefulness. RESULTS AND LIMITATIONS: A total of 914 patients with mRCC were treated with upfront CN during the study period. Seven independently predictive variables were used in the SCREEN score: three or more metastatic sites, total metastatic tumor burden ≥5 cm, bone metastasis, systemic symptoms, low serum hemoglobin, low serum albumin, and neutrophil/lymphocyte ratio ≥4. Predictive accuracy measured as the area under the receiver operating characteristic curves was 0.76 for the SCREEN score and 0.55 for the IMDC model. Decision curve analysis showed that the SCREEN model was useful beyond the IMDC classifier for threshold first-year mortality probabilities between 15% and 70%. CONCLUSIONS: The SCREEN score had higher predictive accuracy for first-year mortality compared to the IMDC scheme in a multi-institutional cohort and may be used to improve CN selection. PATIENT SUMMARY: This study provides a model to improve selection of patients with metastatic kidney cancer who may benefit from surgical removal of the primary kidney tumor. We found that radiographic measurements of the tumor burden predicted the risk of death in the first year after surgery. The model can be used to improve decision-making by these patients and their physicians.

Non-Metastatic Clear Cell Renal Cell Carcinoma Immune Cell Infiltration Heterogeneity and Prognostic Ability in Patients Following Surgery.

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.

Genetic analysis of the role of yfiR in the ability of Escherichia coli CFT073 to control cellular cyclic dimeric GMP levels and to persist in the urinary tract.

During urinary tract infections (UTIs), uropathogenic Escherichia coli must maintain a delicate balance between sessility and motility to achieve successful infection of both the bladder and kidneys. Previous studies showed that cyclic dimeric GMP (c-di-GMP) levels aid in the control of the transition between motile and nonmotile states in E. coli. The yfiRNB locus in E. coli CFT073 contains genes for YfiN, a diguanylate cyclase, and its activity regulators, YfiR and YfiB. Deletion of yfiR yielded a mutant that was attenuated in both the bladder and the kidneys when tested in competition with the wild-type strain in the murine model of UTI. A double yfiRN mutant was not attenuated in the mouse model, suggesting that unregulated YfiN activity and likely increased cytoplasmic c-di-GMP levels cause a survival defect. Curli fimbriae and cellulose production were increased in the yfiR mutant. Expression of yhjH, a gene encoding a proven phosphodiesterase, in CFT073 ΔyfiR suppressed the overproduction of curli fimbriae and cellulose and further verified that deletion of yfiR results in c-di-GMP accumulation. Additional deletion of csgD and bcsA, genes necessary for curli fimbriae and cellulose production, respectively, returned colonization levels of the yfiR deletion mutant to wild-type levels. Peroxide sensitivity assays and iron acquisition assays displayed no significant differences between the yfiR mutant and the wild-type strain. These results indicate that dysregulation of c-di-GMP production results in pleiotropic effects that disable E. coli in the urinary tract and implicate the c-di-GMP regulatory system as an important factor in the persistence of uropathogenic E. coli in vivo.

Understanding and integrating cytoreductive nephrectomy with immune checkpoint inhibitors in the management of metastatic RCC.

Cytoreductive nephrectomy became accepted as standard of care for selected patients with metastatic renal cell carcinoma (mRCC) because of improved survival observed in patients treated with cytoreductive nephrectomy in combination with interferon-α in two randomized clinical trials published in 2001. Over the past two decades, novel systemic therapies have shown higher treatment response rates and improved survival outcomes compared with interferon-α. During this rapid evolution of mRCC treatments, systemic therapies have been the primary focus of clinical trials. Results from multiple retrospective studies continue to suggest an overall survival benefit for selected patients treated with nephrectomy in combination with systemic mRCC treatments, with the notable exception of one debated clinical trial. The optimal timing for surgery is unknown, and proper patient selection remains crucial to improving surgical outcomes. As systemic therapies continue to evolve, clinicians have an increasing need to understand how to incorporate cytoreductive nephrectomy into the management of mRCC.

Impact of Agent Orange Exposure on Non-muscle Invasive Bladder Cancer Outcomes.

OBJECTIVE: To explore the effect of Agent Orange (AO) exposure on bladder cancer (BCa) outcomes in patients receiving Bacillus Calmette-Guérin (BCG) for non-muscle invasive BCa (NMIBC). METHODS: We retrospectively examined the association between AO exposure in patients with NMIBC in national veterans affairs databases who were being treated with BCG. Patients were diagnosed with NMIBC from 2000 to 2010 with follow-up through 2018. Clinical, pathological, and demographic variables were compared by AO exposure. Associations of AO exposure with recurrence, progression, and cancer-specific survival were performed using Cox proportional hazard models after inverse propensity score weighting and competing risks adjustments. We also assessed the association of AO exposure on grade and stage via multivariable logistic regression models. RESULTS: A total of 7651 patients were identified of which 753 (9.8%) were exposed to AO. The median follow-up time was 130 months. The AO-exposed patients were younger (age 61 vs 71 years, P <.001), but had similar Charlson comorbidity scores and stage/grade distribution as the non-AO exposed patients. AO exposure was not associated with higher grade or stage. In our Cox multivariable analyses, AO exposure was not associated with worse recurrence (hazard ratio (HR) 0.89, 95% confidence interval (CI) 0.72-1.10, P = .29), progression (HR 1.08, 95% CI 0.86-1.36, P = .51), or cancer-specific survival (HR 1.31, 95% CI 0.92-1.87, P = .13). CONCLUSION: AO exposure was not associated with worse oncologic outcomes in patients receiving BCG for NMIBC. While this is reassuring, additional research is needed in other patient populations and disease states to determine if the effect is consistent.

Understanding the Tumor Immune Microenvironment in Renal Cell Carcinoma.

Scientific understanding of how the immune microenvironment interacts with renal cell carcinoma (RCC) has substantially increased over the last decade as a result of research investigations and applying immunotherapies, which modulate how the immune system targets and eliminates RCC tumor cells. Clinically, immune checkpoint inhibitor therapy (ICI) has revolutionized the treatment of advanced clear cell RCC because of improved outcomes compared to targeted molecular therapies. From an immunologic perspective, RCC is particularly interesting because tumors are known to be highly inflamed, but the mechanisms underlying the inflammation of the tumor immune microenvironment are atypical and not well described. While technological advances in gene sequencing and cellular imaging have enabled precise characterization of RCC immune cell phenotypes, multiple theories have been suggested regarding the functional significance of immune infiltration in RCC progression. The purpose of this review is to describe the general concepts of the anti-tumor immune response and to provide a detailed summary of the current understanding of the immune response to RCC tumor development and progression. This article describes immune cell phenotypes that have been reported in the RCC microenvironment and discusses the application of RCC immunophenotyping to predict response to ICI therapy and patient survival.

Cytoreductive Nephrectomy Following Immune Checkpoint Inhibitor Therapy Is Safe and Facilitates Treatment-free Intervals.

Patients with metastatic renal cell cancer (mRCC) who respond to upfront immune checkpoint inhibitor (ICI) combination therapies may be treated with cytoreductive nephrectomy (CN) to remove radiographically viable primary tumors. Early data for post-ICI CN suggested that ICI therapies induce desmoplastic reactions in some patients, increasing the risk of surgical complications and perioperative mortality. We evaluated perioperative outcomes for 75 consecutive patients treated with post-ICI CN at four institutions from 2017 to 2022. Our cohort of 75 patients had minimal or no residual metastatic disease but radiographically enhancing primary tumors after ICI and were treated with CN. Intraoperative complications were identified in 3/75 patients (4%) and 90-d postoperative complications in 19/75 (25%), including two patients (3%) with high-grade (Clavien ≥III) complications. One patient was readmitted within 30 d. No patients died within 90 d after surgery. Viable tumor was present in all but one specimen. Approximately half of the patients (36/75, 48%) remained off systemic therapy at last follow-up. These data suggest that CN following ICI therapy is safe and associated with low rates of major postoperative complications in appropriately selected patients at experienced centers. Post-ICI CN may facilitate observation without additional systemic therapy in patients without significant residual metastatic disease. Patient summary: Current first-line treatment for patients with kidney cancer that has spread to other sites (metastatic cancer) is immunotherapy. For cases in which metastatic sites respond to this therapy but primary tumor is still detected in the kidney, surgical treatment of the tumor is feasible and has a low rate of complications, and may delay the need for further chemotherapy.

Contemporary Patients Have Better Perioperative Outcomes Following Cytoreductive Nephrectomy: A Multi-institutional Analysis of 1272 Consecutive Patients.

OBJECTIVE: To evaluate factors associated with perioperative outcomes in a multi-institutional cohort of patients treated with cytoreductive nephrectomy (CN). METHODS: Data were analyzed for metastatic renal cell carcinoma patients treated with CN at 6 tertiary academic centers from 2005 to 2019. Outcomes included: Clavien-Dindo complications, mortality, length of hospitalization, 30-day readmission rate, and time to systemic therapy. Univariate and multivariable models evaluated associations between outcomes and prognostic variables including the year of surgery. RESULTS: A total of 1272 consecutive patients were treated with CN. Patients treated in 2015-2019 vs 2005-2009 had better performance status (P<.001), higher pathologic N stage (P = .04), more frequent lymph node dissections (P<.001), and less frequent presurgical therapy (P = .02). Patients treated in 2015-2019 vs 2005-2009 had lower overall and major complications from surgery, 22% vs 39%, P<.001% and 10% vs 16%, P = .03. Mortality at 90days was higher for patients treated 2005-2009 vs 2015-2019; 10% vs 5%, P = .02. After multivariable analysis, surgical time period was an independent predictor of major complications and 90-day mortality following cytoreductive surgery. CONCLUSION: Postoperative major complications and mortality rates following CN are significantly lower in patients treated within the most recent time period.

Neddylation inhibition sensitises renal medullary carcinoma tumours to platinum chemotherapy.

BACKGROUND: Renal medullary carcinoma (RMC) is a highly aggressive cancer in need of new therapeutic strategies. The neddylation pathway can protect cells from DNA damage induced by the platinum-based chemotherapy used in RMC. We investigated if neddylation inhibition with pevonedistat will synergistically enhance antitumour effects of platinum-based chemotherapy in RMC. METHODS: We evaluated the IC50 concentrations of the neddylation-activating enzyme inhibitor pevonedistat in vitro in RMC cell lines. Bliss synergy scores were calculated using growth inhibition assays following treatment with varying concentrations of pevonedistat and carboplatin. Protein expression was assessed by western blot and immunofluorescence assays. The efficacy of pevonedistat alone or in combination with platinum-based chemotherapy was evaluated in vivo in platinum-naïve and platinum-experienced patient-derived xenograft (PDX) models of RMC. RESULTS: The RMC cell lines demonstrated IC50 concentrations of pevonedistat below the maximum tolerated dose in humans. When combined with carboplatin, pevonedistat demonstrated a significant in vitro synergistic effect. Treatment with carboplatin alone increased nuclear ERCC1 levels used to repair the interstrand crosslinks induced by platinum salts. Conversely, the addition of pevonedistat to carboplatin led to p53 upregulation resulting in FANCD2 suppression and reduced nuclear ERCC1 levels. The addition of pevonedistat to platinum-based chemotherapy significantly inhibited tumour growth in both platinum-naïve and platinum-experienced PDX models of RMC (p < .01). CONCLUSIONS: Our results suggest that pevonedistat synergises with carboplatin to inhibit RMC cell and tumour growth through inhibition of DNA damage repair. These findings support the development of a clinical trial combining pevonedistat with platinum-based chemotherapy for RMC.

Models of Renal Cell Carcinoma Used to Investigate Molecular Mechanisms and Develop New Therapeutics.

Modeling renal cell carcinoma is critical to investigating tumor biology and therapeutic mechanisms. Multiple systems have been developed to represent critical components of the tumor and its surrounding microenvironment. Prominent in vitro models include traditional cell cultures, 3D organoid models, and microphysiological devices. In vivo models consist of murine patient derived xenografts or genetically engineered mice. Each system has unique advantages as well as limitations and researchers must thoroughly understand each model to properly investigate research questions. This review addresses common model systems for renal cell carcinoma and critically evaluates their performance and ability to measure tumor characteristics.

Increased body mass index is associated with operative difficulty during robot-assisted radical prostatectomy.

Objective: This study aimed to identify factors associated with surgeon perception of robot-assisted radical prostatectomy (RARP) difficulty. Patients and Methods: This study surveyed surgeons performing RARP between 2017 and 2018 and asked them to rate operative conditions and difficulty as optimal, good, acceptable, or poor. These answers were stratified as optimal or suboptimal for this study. Associations between surgeon responses and variables hypothesized to affect surgical difficulty, including anatomic factors such as pelvic diameter and prostate volume:pelvic diameter ratio, were assessed. Results: Between November 2017 and September 2018, a total of 100 patients were prospectively enrolled in the study of which 58 cases were rated as optimal and 42 were rated as suboptimal. Of the evaluated variables, only increasing clinical T stage (odds ratio [OR] 1.49, 95% confidence interval [CI] 1.03-2.15, p = 0.03) and increasing body mass index (BMI) (OR 1.14, 95% CI 1.03-1.26, p = 0.01) were associated with increased difficulty; 90-day complication rates were similar between the optimal and suboptimal cohorts (17.3% vs. 23.8%, respectively; p = 0.5). The number of patients with previous surgery, pelvic diameter, and prostate size:pelvic diameter ratio were not significantly different between cohorts (p > 0.05 for all). Operative time (ρ = 0.23, p = 0.02) and estimated blood loss (EBL) (ρ = 0.38, p = 0.0001) were correlated with suboptimal difficulty. Conclusion: The factors associated with surgeon-reported RARP difficulty were patient BMI and clinical T stage among surgeons with significant RARP experience. These data should be incorporated into surgical decision making and patient counseling prior to performing a RARP.