Defining the cellular origin of seminoma by transcriptional and epigenetic mapping to the normal human germline.

Aberrant male germline development can lead to the formation of seminoma, a testicular germ cell tumor. Seminomas are biologically similar to primordial germ cells (PGCs) and many bear an isochromosome 12p [i(12p)] with two additional copies of the short arm of chromosome 12. By mapping seminoma transcriptomes and open chromatin landscape onto a normal human male germline trajectory, we find that seminoma resembles premigratory/migratory PGCs; however, it exhibits enhanced germline and pluripotency programs and upregulation of genes involved in apoptosis, angiogenesis, and MAPK/ERK pathways. Using pluripotent stem cell-derived PGCs from Pallister-Killian syndrome patients mosaic for i(12p), we model seminoma and identify gene dosage effects that may contribute to transformation. As murine seminoma models do not exist, our analyses provide critical insights into genetic, cellular, and signaling programs driving seminoma transformation, and the in vitro platform developed herein permits evaluation of additional signals required for seminoma tumorigenesis.

A mindful approach to complications: Brief review of the literature and practical guide for the surgeon.

Patient complications and adverse outcomes are inherent to surgical practice and training. In addition to the impact on patients, there are profound and well-documented impacts of complications on surgeons, surgical trainees, and surgical teams. This manuscript reviews the literature regarding mindfulness-based practices and the associated mitigation of the adverse impact of complications. These mindfulness-based practices prepare surgeons for complications by improving mental and cognitive resilience facilitating more effective management of complications that avoids undue psychological and emotional stress. Practical recommendations are provided for the practicing surgeon from providers experienced in mindfulness-based training and preparation.

Perioperative nivolumab versus observation in patients with renal cell carcinoma undergoing nephrectomy (PROSPER ECOG-ACRIN EA8143): an open-label, randomised, phase 3 study.

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.

Plasma Kidney Injury Molecule-1 for Preoperative Prediction of Renal Cell Carcinoma Versus Benign Renal Masses, and Association With Clinical Outcomes.

PURPOSE: Both clear cell and papillary renal cell carcinomas (RCCs) overexpress kidney injury molecule-1 (KIM-1). We investigated whether plasma KIM-1 (pKIM-1) may be a useful risk stratification tool among patients with suspicious renal masses. METHODS: Prenephrectomy pKIM-1 was measured in two independent cohorts of patients with renal masses. Cohort 1, from the prospective K2 trial, included 162 patients found to have clear cell RCC (cases) and 162 patients with benign renal masses (controls). Cohort 2 included 247 patients with small (cT1a) renal masses from an academic biorepository, of whom 184 had RCC. We assessed the relationship between pKIM-1, surgical pathology, and clinical outcomes. RESULTS: In Cohort 1, pKIM-1 distinguished RCC versus benign masses with area under the receiver operating curve (AUC-ROC, 0.81 [95% CI, 0.76 to 0.86]). In Cohort 2 (cT1a only), pKIM-1 distinguished RCC versus benign masses (AUC-ROC, 0.74 [95% CI, 0.67 to 0.80]) and the addition of pKIM-1 to an established nomogram for predicting malignancy improved the model AUC-ROC (0.65 [95% CI, 0.57 to 0.74] v 0.78 [95% CI, 0.72 to 0.85]). A pKIM-1 cutpoint identified using Cohort 2 demonstrated sensitivity of 92.5% and specificity of 60% for identifying RCC in Cohort 1. In long-term follow-up of RCC cases (Cohort 1), higher prenephrectomy pKIM-1 was associated with worse metastasis-free survival (multivariable MFS hazard ratio [HR] 1.29 per unit increase in log pKIM-1, 95% CI, 1.10 to 1.53) and overall survival (multivariable OS HR 1.31 per unit increase in log pKIM-1, 95% CI, 1.10 to 1.54). In long-term follow-up of Cohort 2, no metastatic events occurred, consistent with the favorable prognosis of resected cT1a RCC. CONCLUSION: Among patients with renal masses, pKIM-1 is associated with malignant pathology, worse MFS, and risk of death. pKIM-1 may be useful for selecting patients with renal masses for intervention versus surveillance.

Prostate-Specific Antigen Screening in Smokers: A Comprehensive Analysis Using a National Behavioral Survey.

INTRODUCTION: Cigarette smoking is associated with higher-risk prostate cancer at the time of diagnosis and increased overall and prostate cancer‒specific mortality. Previous studies indicate smokers are less likely to undergo PSA screening. Herein we investigate the association between smoking and PSA screening using a nationally representative US survey. We hypothesize that smokers are less likely to undergo guideline-concordant PSA screening. METHODS: We performed a cross-sectional analysis of men aged 55 to 69 who responded to the cigarette smoking and PSA screening questions of the 2018 Behavioral Risk Factor Surveillance System survey. Adjusted prevalence and adjusted risk differences were calculated using complex weighted multivariable Poisson regression modeling. RESULTS: We identified 58,996 individuals who qualified for analysis. PSA screening prevalence was 39% (95% CI: 39%-40%) nationally, 42% (95% CI: 41%-44%) for never smokers, 42% (95% CI: 39%-40%) for former smokers, and 27% (95% CI: 25%-29%) for current smokers, including 27% (95% CI: 24%-29%) for daily smokers and 29% (95% CI: 24%-33%) for nondaily smokers. Compared to never smokers, the adjusted relative risk for undergoing PSA screening was 0.81 for current smokers (95% CI: 0.75-0.88, P < .01) and 0.99 for former smokers (95% CI: 0.94-1.03, P = .53). CONCLUSIONS: Current smokers are less likely to undergo recommended PSA screening, but former smokers are screened at similar rates as never smokers. As delays in diagnosis may substantially contribute to worse prostate cancer outcomes, targeted interventions to increase screening in this population may yield significant effects.

Rate of benign histology after resection of suspected renal cell carcinoma: multicenter comparison between Korea and the United States.

BACKGROUND: In the United States, the rate of benign histology among resected renal tumors suspected to be malignant is increasing. We evaluated the rates in the Republic of Korea and assessed the racial effect using recent multi-institutional Korean-United States data. METHODS: We conducted a multi-institutional retrospective study of 11,529 patients (8,812 from The Republic of Korea and 2,717 from the United States) and compared the rates of benign histology between the two countries. To evaluate the racial effect, we divided the patients into Korean, Asian in the US, and Non-Asian in the US. RESULTS: The rates of benign histology and small renal masses in Korean patients were significantly lower than that in United States patients (6.3% vs. 14.3%, p < 0.001) and (≤ 4 cm, 7.6% vs. 19.5%, p < 0.001), respectively. Women, incidentaloma, partial nephrectomy, minimally invasive surgery, and recent surgery were associated with a higher rate of benign histology than others. CONCLUSIONS: In Korea, the rate of benign histology among resected renal tumors was significantly lower than that in the United States. This disparity could be caused by environmental or cultural differences rather than racial differences. Our findings suggest that re-evaluating current context-specific standards of care is necessary to avoid overtreatment.

Urologist-level variation in the management of T1a renal cell carcinoma: A population-based cohort study.

OBJECTIVES: Lack of strict indications in current guidelines have led to significant variation in management patterns of small renal masses. The impact of the urologist on the management approach for patients with small renal masses has not been explored previously. MATERIALS AND METHODS: Using the linked Surveillance, Epidemiology, and End Results-Medicare database, patients aged ≥66 years diagnosed with small renal masses from January 1, 2004 to December 31, 2013 were identified and assigned to primary urologists. Mixed-effects logistic models were used to evaluate factors associated with different management approaches, estimate urologist-level probabilities of each approach, assess management variation, and determine urologist impact on choice of approach. RESULTS: A total of 12,402 patients with 2,794 corresponding primary urologists were included in the study. At the individual urologist level, the estimated case-adjusted probability of different approaches varied markedly: nonsurgical management (mean, 12.8%; range, 4.9%-36.1%); thermal ablation (mean, 10.8%; range, 2.4%-66.3%); partial nephrectomy (mean, 30.1%; range, 10.1%-66.6%); and radical nephrectomy (mean, 40.4%; range, 17.7%-71.6%). Compared to patient and tumor characteristics, the primary urologist was a more influential measured factor, accounting for 13.6% (vs. 12.9%), 33.8% (vs. 2.1%), 15.1% (vs. 8.4%), and 13.5% (vs. 4.0%) of the variation in management choice for nonsurgical management, thermal ablation, partial nephrectomy, and radical nephrectomy, respectively. CONCLUSIONS: Significant variation exists in the management of small renal masses and appears to be driven primarily by urologist preference and practice patterns. Our findings emphasize the need for unified guidance regarding management of these masses to reduce unwarranted variation in care.

Immunomodulatory response to neoadjuvant nivolumab in non-metastatic clear cell renal cell carcinoma.

Novel perioperative strategies are needed to reduce recurrence rates in patients undergoing nephrectomy for high-risk, non-metastatic clear cell renal cell carcinoma (ccRCC). We conducted a prospective, phase I trial of neoadjuvant nivolumab prior to nephrectomy in 15 evaluable patients with non-metastatic ccRCC. We leveraged tissue from that cohort to elucidate the effects of PD-1 inhibition on immune cell populations in ccRCC and correlate the evolving immune milieu with anti-PD-1 response. We found that nivolumab durably induces a pro-inflammatory state within the primary tumor, and baseline immune infiltration within the primary tumor correlates with nivolumab responsiveness. Nivolumab increases CTLA-4 expression in the primary tumor, and subsequent nephrectomy increases circulating concentrations of sPD-L1, sPD-L3 (sB7-H3), and s4-1BB. These findings form the basis to consider neoadjuvant immune checkpoint inhibition (ICI) for high-risk ccRCC while the tumor remains in situ and provide the rationale for perioperative strategies of novel ICI combinations.

Racial differences in knowledge, attitudes, and sources of information about germline cancer genetic testing in the U.S.A.: An analysis of the health information National Trends Survey System.

PURPOSE: To understand racial disparities in germline cancer genetic testing and the role of prior knowledge, attitudes, and sources of information. METHODS: A cross-sectional analysis of the Health Information National Trends Survey 5 (HINTS 5) was conducted between February 24th and June 15th, 2020. The study aimed to investigate knowledge and receipt of genetic testing, attitudes toward the importance of genetic testing in preventing, detecting, and treating cancer, and information sources of genetic testing in the United States of America. RESULTS: Non-Hispanic Black (NHB) and Hispanic race/ethnicity were associated with lower odds of being informed about genetic testing, whereas those of NHB race were more likely to endorse the importance of genetic testing in cancer prevention and treatment. Regarding sources of information about genetic testing: Non-Hispanic Asians were less likely to be informed about genetic testing from television (Mean Predicted Probability (MPP) 0.38 95%CI; 0.21-0.55, (Adjusted Risk Difference) ARD vs. Non-Hispanic White (NHW); -0.228, p = 0.01), NHB were less likely to report being informed about genetic testing from social media (MPP 0.27 95%CI; 0.20-0.34, ARD vs. NHW; -0.139, p < 0.01). CONCLUSIONS: NHB and Hispanic groups face unequal access to information about genetic testing. There are significant race-based differences in information sources. These differences could be used to promote equitable access to cancer genetic testing.

Kidney Immune Cell Characterization of Humanized Mouse Models.

Experimental studies often fail to translate to clinical practice. Humanized mouse models are an important tool to close this gap. We immunophenotyped the kidneys of NOG (EXL) and NSG mouse strains engrafted with human CD34 + hematopoietic stem cells or PBMCs and compared with immune cell composition of normal human kidney. Human CD34 + hematopoietic stem cell engraftment results in steady renal immune cell populations in mouse kidney with key similarities in composition compared with human kidney. Successful translation of experimental mouse data to human diseases is limited because of biological differences and imperfect disease models. Humanized mouse models are being used to bring murine models closer to humans. However, data for application in renal immune cell-mediated diseases are rare. We therefore studied immune cell composition of three different humanized mouse kidneys and compared them with human kidney. NOG and NOGEXL mice engrafted with human CD34 + hematopoietic stem cells were compared with NSG mice engrafted with human PBMCs. Engraftment was confirmed with flow cytometry, and immune cell composition in kidney, blood, spleen, and bone marrow was analyzed in different models. The results from immunophenotyping of kidneys from different humanized mouse strains were compared with normal portions of human kidneys. We found significant engraftment of human immune cells in blood and kidney of all tested models. huNSG mice showed highest frequencies of hTCR + cells compared with huNOG and huNOGEXL in blood. huNOGEXL was found to have the highest hCD4 + frequency among all tested models. Non-T cells such as hCD20 + and hCD11c + cells were decreased in huNSG mice compared with huNOG and huNOGEXL. Compared with normal human kidney, huNOG and huNOGEXL mice showed representative immune cell composition, rather than huNSG mice. In summary, humanization results in immune cell infiltration in the kidney with variable immune cell composition of tested humanized mouse models and partially reflects normal human kidneys, suggesting potential use for translational studies.

Diagnosis and Treatment of Early-Stage Testicular Cancer: AUA Guideline Amendment 2023.

PURPOSE: The purpose of this American Urological Association (AUA) guideline amendment is to provide a useful reference on the effective evidence-based treatment strategies for early-stage testicular cancer. METHODOLOGY/METHODS: The original methodology protocol included searches of PubMed®, Embase®, and the Cochrane Central Register of Controlled Trials (CENTRAL) from January 1980 through August 2018. The search strategy used medical subject heading (MeSH) terms and key words relevant to the diagnosis and treatment of early-stage testicular cancer. The searches conducted for the update presented herein utilized the same methodological protocol to capture literature published through March 2023. When sufficient evidence existed, the body of evidence was assigned a strength rating of A (high), B (moderate), or C (low) for support of Strong, Moderate, or Conditional Recommendations. In the absence of sufficient evidence, additional information is provided as Clinical Principles and Expert Opinions. RESULTS: Updates were made to statements on imaging, seminoma management, non-seminoma management, surveillance for stage I testicular cancer, and additional survivorship. Further revisions were made to the methodology and reference sections as appropriate. CONCLUSIONS: This guideline seeks to improve clinicians' ability to evaluate and treat patients with early-stage testicular cancer based on currently available evidence. Future studies will be essential to further support or refine these statements to improve patient care.

The national utilization of nonoperative management for small renal masses over 10 years.

BACKGROUND: Management of small renal masses often involves a nonoperative approach, but there is a paucity of information about the use and associated predictors of such approaches. This study aimed to determine the trends in and predictors of use of nonoperative management of small renal masses. METHODS: Using data from the National Cancer Database for localized small renal masses (N0/M0, cT1a) diagnosed between 2010 and 2020, we conducted a cross-sectional study. Nonoperative management was defined as expectant management (active surveillance or watchful waiting) or focal ablation. Adjusted odds ratios (AORs) were calculated using multivariable logistic regression models. RESULTS: Of the 156 734 patients included, 10.5% underwent expectant management, and 13.9% underwent focal ablation. Later year of diagnosis was associated with a higher likelihood of nonoperative management. In 2020, the odds of receiving expectant management and focal ablation were 90% (AOR = 1.90, 95% confidence interval [CI] = 1.71 to 2.11) and 44% (AOR = 1.44, 95% CI = 1.31 to 1.57) higher, respectively, than in 2010. Black patients had increased odds of expectant management (AOR = 1.47, 95% CI = 1.39 to 1.55) but decreased odds of focal ablation (AOR = 0.93, 95% CI = 0.88 to 0.99). CONCLUSION: Over the decade, the use nonoperative management of small renal masses increased, with expectant management more frequently used than focal ablation among Black patients. Possible explanations include race-based differences in physicians' risk assessments and resource allocation. Adjusting for Black race in calculations for glomerular filtration rate could influence the differential uptake of these techniques through deflated glomerular filtration rate calculations. These findings highlight the need for research and policies to ensure equitable use of less invasive treatments in small renal masses.

Diabetes, Obesity, and Pathological Upstaging in Renal Cell Carcinoma: Results From a Large Multi-institutional Consortium.

PURPOSE: We sought to determine whether clinical risk factors and morphometric features on preoperative imaging can be utilized to identify those patients with cT1 tumors who are at higher risk of upstaging (pT3a). MATERIALS AND METHODS: We performed a retrospective international case-control study of consecutive patients treated surgically with radical or partial nephrectomy for nonmetastatic renal cell carcinoma (cT1 N0) conducted between January 2010 and December 2018. Multivariable logistic regression models were used to study associations of preoperative risk factors on pT3a pathological upstaging among all patients, as well as subsets with those with preoperative tumors ≤4 cm, renal nephrometry scores, tumors ≤4 cm with nephrometry scores, and clear cell histology. We also examined association with pT3a subsets (renal vein, sinus fat, perinephric fat). RESULTS: Among the 4,092 partial nephrectomy and 2,056 radical nephrectomy patients, pathological upstaging occurred in 4.9% and 23.3%, respectively. Among each group independent factors associated with pT3a upstaging were increasing preoperative tumor size, increasing age, and the presence of diabetes. Specifically, among partial nephrectomy subjects diabetes (OR=1.65; 95% CI 1.17, 2.29), male sex (OR=1.62; 95% CI 1.14, 2.33), and increasing BMI (OR=1.03; 95% CI 1.00, 1.05 per 1 unit BMI) were statistically associated with upstaging. Subset analyses identified hilar tumors as more likely to be upstaged (partial nephrectomy OR=1.91; 95% CI 1.12, 3.16; radical nephrectomy OR=2.16; 95% CI 1.44, 3.25). CONCLUSIONS: Diabetes and higher BMI were associated with pathological upstaging, as were preoperative tumor size, increased age, and male sex. Similarly, hilar tumors were frequently upstaged.

Transperitoneal Versus Retroperitoneal Robotic-Assisted Partial Nephrectomy in Patients with Obesity.

Introduction: We aim to compare transperitoneal (TP) and retroperitoneal (RP) robotic partial nephrectomy (RPN) in obese patients. Obesity and RP fat can complicate RPN, especially in the RP approach where working space is limited. Materials and Methods: Using a multi-institutional database, we analyzed 468 obese patients undergoing RPN for a renal mass (86 [18.38%] RP, 382 [81.62%] TP). Obesity was defined as body mass index ≥30 kg/m2*. A 1:1 propensity score matching was performed adjusting for age, previous abdominal surgery, tumor size, R.E.N.A.L nephrometry score, tumor location, surgical date, and participating centers. Baseline characteristics and perioperative and postoperative data were compared. Results: In the propensity score-matched cohort, 79 (50%) TP patients were matched with 79 (50%) RP patients. The RP group had more posterior tumors (67 [84.81%], RP versus 23 [29.11%], TP; P < .001), while the other baseline characteristics were comparable. Warm ischemia time (interquartile range; 15 [10, 12], RP versus 14 [10, 17] minutes, TP; P = .216), operative time (129 [116, 165], RP versus 130 [95, 180] minutes, TP; P = .687), estimated blood loss (50 [50, 100], RP versus 75 [50, 150] mL, TP; P = .129), length of stay (1 [1, 1], RP versus 1 [1, 2] day, TP; P = .319), and major complication rate (1 [1.27%], RP versus 3 [3.80%], TP; P = .620) were similar. No significant difference was observed in positive surgical margin rate and delta estimated glomerular filtration at follow-up. Conclusion: TP and RP RPN yielded similar perioperative and postoperative outcomes in obese patients. Obesity should not be a factor in determining optimal approach for RPN.

Robot-assisted partial nephrectomy for complex renal tumors: Analysis of a large multi-institutional database.

INTRODUCTION: Highly complex renal masses pose a challenge to urologic surgeons' ability to perform robotic partial nephrectomy (RPN). Given the increased utilization of the robotic approach for small renal masses, we sought to characterize the outcomes and determine the safety and feasibility of RPN for complex renal masses from our large multi-institutional cohort. METHODS: We performed a retrospective analysis of patients with R.E.N.A.L. Nephrometry Scores ≥10 who underwent RPN in our multi-institutional cohort (N = 372). Baseline demographic, clinical and tumor related characteristics were evaluated with the primary endpoint of trifecta achievement (defined as negative surgical margin, no major complications, and warm ischemia time ≤25 min). Relationships between variables were assessed using the chi-square test of independence, Fisher exact test, Mann-Whitney U test, and Kruskal Wallis test. Logistic regression was used to evaluate the relationship between baseline characteristics and trifecta achievement. RESULTS: Of 372 patients in the study, mean age was 58 years, and median BMI was 30.49 kg/m2. The median tumor size was 4.3 cm (3.0-5.9 cm). Most of the patients had R.E.N.A.L. scores of 10 (n = 253; 67.01%). Overall, trifecta was achieved in 72.04% of patients. Stratifying intraoperative and postoperative outcomes by R.E.N.A.L. scores, there was no significant difference in trifecta achievement, operative time, warm ischemia time (WIT), open conversion, major complication, or positive margin rates. Length of hospital stay was significantly longer for higher R.E.N.A.L. scores (median days 2 vs. 1, P = 0.012). Multivariate analyses for factors associated with trifecta achievement concluded that age and baseline eGFR were independently associated with trifecta achievement. CONCLUSION: RPN is a safe and reproducible procedure for complex tumors with R.E.N.A.L. Nephrometry scores ≥10. Our results suggest excellent rates of trifecta achievement and short-term functional outcomes when performed by experienced surgeons. Long-term oncological and functional evaluation are needed to further support this conclusion.

ACR Appropriateness Criteria® Staging of Renal Cell Carcinoma: 2022 Update.

Renal cell carcinoma is a complex group of highly heterogenous renal tumors demonstrating variable biological behavior. Pretreatment imaging of renal cell carcinoma involves accurate assessment of the primary tumor, presence of nodal, and distant metastases. CT and MRI are the key imaging modalities used in the staging of renal cell carcinoma. Important imaging features that impact treatment include tumor extension into renal sinus and perinephric fat, involvement of pelvicalyceal system, infiltration into adrenal gland, involvement of renal vein and inferior vena cava, as well as the presence of metastatic adenopathy and distant metastases. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.