Genomic ancestry in kidney cancer: Correlations with clinical and molecular features.

INTRODUCTION: Genetic ancestry (GA) refers to population hereditary patterns that contribute to phenotypic differences seen among race/ethnicity groups, and differences among GA groups may highlight unique biological determinants that add to our understanding of health care disparities. METHODS: A retrospective review of patients with renal cell carcinoma (RCC) was performed and correlated GA with clinicopathologic, somatic, and germline molecular data. All patients underwent next-generation sequencing of normal and tumor DNA using Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets, and contribution of African (AFR), East Asian (EAS), European (EUR), Native American, and South Asian (SAS) ancestry was inferred through supervised ADMIXTURE. Molecular data was compared across GA groups by Fisher exact test and Kruskal-Wallis test. RESULTS: In 953 patients with RCC, the GA distribution was: EUR (78%), AFR (4.9%), EAS (2.5%), SAS (2%), Native American (0.2%), and Admixed (12.2%). GA distribution varied by tumor histology and international metastatic RCC database consortium disease risk status (intermediate-poor: EUR 58%, AFR 88%, EAS 74%, and SAS 73%). Pathogenic/likely pathogenic germline variants in cancer-predisposition genes varied (16% EUR, 23% AFR, 8% EAS, and 0% SAS), and most occurred in CHEK2 in EUR (3.1%) and FH in AFR (15.4%). In patients with clear cell RCC, somatic alteration incidence varied with significant enrichment in BAP1 alterations (EUR 17%, AFR 50%, SAS 29%; p = .01). Comparing AFR and EUR groups within The Cancer Genome Atlas, significant differences were identified in angiogenesis and inflammatory pathways. CONCLUSION: Differences in clinical and molecular data by GA highlight population-specific variations in patients with RCC. Exploration of both genetic and nongenetic variables remains critical to optimize efforts to overcome health-related disparities.

Gerontological education: a pathway towards advancing the rights of older people.

Following the UN Human Rights Declaration in 1948, much effort has been undertaken to formalize the rights of older people. This article aims to highlight the role of education in advancing the rights of older people. Raising awareness and sharing knowledge about the rights of older people through rights-based education can empower students, when entering their field of work, to be advocates for rights within their employment settings and local communities. The effectiveness of a rights-based educational training for organizations working with refugees in Jordan, which took place in Amman in January 2020, is analyzed using the participant-focused Transformative Human Rights Education (THRED) as a framing structure. Our analysis found that training participants became active in promoting the rights of older people in their workplaces. The rights of older people need to be more than a conversation, and transformational change that promotes rights can occur when people feel empowered to undertake action-oriented advocacy. The case study analysis provides an example of how influential participant-centered pedagogy, such as THRED, can be to help students in gerontology programs become active agents in promoting rights of older people in their workplaces, communities, and ultimately influencing the international dialogue.

Personalizing First-Line Management of Metastatic Renal Cell Carcinoma: Leveraging Current and Novel Therapeutic Options.

The treatment of metastatic renal cell carcinoma (RCC) has been revolutionized by advances in immunotherapeutic and targeted agents. Therapeutic approaches to RCC in these categories have recently evolved to include immune checkpoint inhibitors, novel vascular endothelial growth factor receptor-targeting tyrosine kinase inhibitors, and combinations of those agents. Multiple regimens within each category have been approved for use in the first-line treatment of clear cell and non-clear cell RCC. However, few of these regimens have been directly compared, leading to a new clinical challenge for physicians: how to select a first-line treatment regimen for an individual patient from among multiple approved options. In the modern era of RCC management, the initial treatment selection therefore becomes highly personalized and depends on numerous patient-specific factors, including histopathologic and clinical features of the disease, comorbid conditions, and psychosocial and economic factors. This review details current first-line treatment options for the management of metastatic RCC and proposes a framework whereby treatment selection can be optimized for individual patients.

Perioperative Antibiotics and Other Factors Associated with Postcesarean Infections: A Case-Control Study.

OBJECTIVE: Our objective was to determine modifiable risk factors associated with surgical site infection (SSI) and postpartum endometritis. We hypothesized that inappropriate surgical antibiotic prophylaxis would be a risk factor for both types of infections. STUDY DESIGN: This was a single-center case-control study of SSI and endometritis after cesarean delivery over a 2-year period from 2016 to 2017. Cases were identified by International Classification of Diseases, 10th Revision diagnosis codes, infection control surveillance, and electronic medical records search and were subsequently confirmed by chart review. Three controls were randomly selected for each case from all cesareans ± 48 hours from case delivery. Demographic, pregnancy, and delivery characteristics were abstracted. Separate multivariable logistic regression models were used to assess factors associated with SSI and endometritis. Postpartum outcomes, including length of stay and readmission, were also compared. RESULTS: We identified 141 cases of SSI and endometritis with an overall postpartum infection rate of 4.0% among all cesarean deliveries. In adjusted analysis, factors associated with both SSI and endometritis were intrapartum delivery, classical or other (non-low-transverse) uterine incision, and blood transfusion. Factors associated with SSI only included inadequate antibiotic prophylaxis, public insurance, hypertensive disorder of pregnancy, and nonchlorhexidine abdominal preparation; factors only associated with endometritis included ß-lactam allergy, anticoagulation therapy, and chorioamnionitis. Among cases, 34% of those with SSI and 25% of those with endometritis did not receive adequate antibiotic prophylaxis, compared with 12.9 and 13.5% in control groups, respectively. Failure to receive appropriate antibiotic prophylaxis was associated with an increased risk of SSI (adjusted odds ratio [aOR]: 4.4, 95% confidence interval [CI]: 1.3-15.6) but not endometritis (aOR 0.9, 95% CI 0.4-2.0). CONCLUSION: Inadequate surgical antibiotic prophylaxis was associated with an increased risk of SSI but not postpartum endometritis, highlighting the different mechanisms of these infections and the importance of prioritizing adequate surgical prophylaxis. Additional potentially modifiable factors which emerged included blood transfusion and chlorhexidine skin preparation. KEY POINTS: · Inadequate antibiotic prophylaxis is associated with a four-fold risk in surgical site infections.. · The most common cause for failure to achieve adequate surgical prophylaxis was inappropriate timing of antibiotics at or after skin incision.. · Blood transfusions are strongly associated (>10-fold risk) with both SSI and endometritis..

Engaged Scholarship in Gerontology: Frank Caro's Lifetime Contributions.

Dr. Francis G. Caro, retired Professor of Gerontology at the University of Massachusetts Boston, Co-editor (1996-2005) and Editor-in-Chief (2005-2016) of the Journal of Aging and Social Policy, passed away on October 2, 2020. Caro dedicated most of his nearly 60 years of academic and professional activity to gerontology and services for older adults. This article offers a review of his contributions in four central areas of gerontology: the strengthening of long-term services and supports through integration of home care services with other domains, the expansion of how productive aging was socially understood and economically valued, the importance of rigorous program evaluation and ongoing methodological innovation, and the significance of age-friendly cities and communities, both in the United States and internationally. This review of Caro's work highlights his integral role in helping to place several topics on the gerontological agenda that are still relevant today, establishing him as an important contributor to the field. He also exemplified productive aging and how scholarship can be theoretically rigorous but also applied in meaningful ways to make a difference in individual lives and within communities.

Outcomes of a Negative Rapid Influenza Diagnostic Test in Pregnant Women.

OBJECTIVE: The objective of this study was to evaluate the negative predictive value (NPV) of a rapid influenza diagnostic test (RIDT) compared with polymerase chain reaction (PCR) in pregnant women. STUDY DESIGN: Retrospective cohort study of pregnant women with a negative RIDT followed by confirmatory PCR for influenza A, H1N1, and B during the influenza seasons from 2012 to 2015. RESULTS: The NPV of the RIDT was 85.4% (211 of 247), 93.5% (231 of 247), and 97.9% (242 of 247) for influenza A, H1N1, and B, respectively. Antiviral treatment was administered to 47.2% (17 of 36) of women with a false-negative RIDT for influenza A compared with 9.0% (19 of 211) of women with a true-negative RIDT (p< 0.001). Patients were more likely to receive antiviral treatment if they were feverish (adjusted odds ratio [aOR]: 6.05, 95% confidence interval [CI]: 1.83-20.03), had cough (aOR: 6.43, 95% CI: 1.06-39.26), dyspnea (aOR: 6.41, 95% CI: 1.63-25.29), or had a subsequently positive PCR (aOR: 9.41, 95% CI: 3.13-28.31). CONCLUSION: Up to 14.5% of women with a negative RIDT in pregnancy had positive influenza A by PCR of whom more than half did not receive antiviral treatment.

Re-engineering the Immune Response to Metastatic Cancer: Antibody-Recruiting Small Molecules Targeting the Urokinase Receptor.

Developing selective strategies to treat metastatic cancers remains a significant challenge. Herein, we report the first antibody-recruiting small molecule (ARM) that is capable of recognizing the urokinase-type plasminogen activator receptor (uPAR), a uniquely overexpressed cancer cell-surface marker, and facilitating the immune-mediated destruction of cancer cells. A co-crystal structure of the ARM-U2/uPAR complex was obtained, representing the first crystal structure of uPAR complexed with a non-peptide ligand. Finally, we demonstrated that ARM-U2 substantially suppresses tumor growth in vivo with no evidence of weight loss, unlike the standard-of-care agent doxorubicin. This work underscores the promise of antibody-recruiting molecules as immunotherapeutics for treating cancer.

Chemically synthesized molecules with the targeting and effector functions of antibodies.

This article reports the design, synthesis, and evaluation of a novel class of molecules of intermediate size (approximately 7000 Da), which possess both the targeting and effector functions of antibodies. These compounds­called synthetic antibody mimics targeting prostate cancer (SyAM-Ps)­bind simultaneously to prostate-specific membrane antigen and Fc gamma receptor I, thus eliciting highly selective cancer cell phagocytosis. SyAMs have the potential to combine the advantages of both small-molecule and biologic therapies, and may address many drawbacks associated with available treatments for cancer and other diseases.

What can I do with a doctoral degree in gerontology? Expanding your options.

An endless number of career trajectories are possible for gerontologists. With a growing aging population, our skills and areas of expertise are of high value to numerous industries. The purpose of this study is to describe the professional development and career trajectories of alumni of U.S. doctoral gerontology programs obtained through the Gerontology Education Longitudinal Study (GELS). Specifically, the authors examine how professional identification, doctoral program career preparation, and perception of job prospects affect alumni decisions to pursue "traditional" (i.e., academic) versus "nontraditional" (i.e., non-academic) careers. Results from the GELS revealed a fairly even split in the alumni sample of careers in traditional and nontraditional settings. The decision to pursue a traditional versus nontraditional career was not significantly associated with personal identification, doctoral program career preparation, or perception of employment options. These results suggest that the skill set obtained in doctoral gerontology programs is useful and is in demand in a variety of careers; therefore, doctoral programs may want to consider tailoring training to meet students' future career goals in both academic and non-academic settings.

Accuracy, readability, and quality of websites about metastatic renal cell carcinoma treatment.

OBJECTIVES: Patients with metastatic renal cell carcinoma (mRCC) face complex treatment decisions and frequently turn to the Internet for treatment information. The content of patient educational websites about mRCC treatment has not been evaluated. This study evaluated the accuracy, readability, and quality of websites about the treatment of mRCC. METHODS: A total of 2,700 Internet queries were performed. Across 3 Internet search engines, 25 links of 36 permutations of mRCC keywords and their synonyms were screened for eligibility. Eligible websites were English-language websites containing information about mRCC treatments. Sponsored, social media, provider-facing, and news websites were excluded. Accuracy of eligible websites was evaluated in 2 domains: (1) Completeness by calculating the percentage of mRCC facts included in websites using an investigator-created checklist based on the NCI's RCC Treatment (PDQ®)-patient version, and (2) Correctness by identifying incorrect statements that were inconsistent with guidelines. Websites containing ≥60% of checklist items had a "passing" completeness score. Incorrect statements were tallied and qualitatively categorized. Readability was evaluated using the Fry and SMOG formulae, which calculate reading grade levels. Quality was evaluated using validated instruments that appraise health information quality: QUEST (scored 0-28), which focuses on online information, and DISCERN (scored 16-80), which focuses on treatment choices. RESULTS: Thirty-nine websites were analyzed. Mean completeness score was 30% (range 0%-69%); only 2 (5%) websites had a passing score. Twelve (31%) websites had ≥1 incorrect statement, such as listing homeopathy or hormone therapy as mRCC treatment options, or including outdated statements. Mean readability levels were 11th and 12th grades for the Fry and SMOG methods, respectively. No website had a reading level lower than 9th grade. Mean QUEST score was 19 (range 9-28); authorship, complementarity, and currency items had the lowest scores. Mean DISCERN score was 56 (range 42-76), with 7 (18%) websites rated "excellent", 22 (56%) rated "good", and 10 (26%) rated fair. CONCLUSIONS: Many websites about mRCC treatment have incomplete, inaccurate, and unreadable information. Quality is highly variable. Efforts to improve accuracy, readability, and quality are needed to ensure that patients with mRCC can make well-informed treatment decisions and avoid harm from misinformation.

Edge roughness quantifies impact of physician variation on training and performance of deep learning auto-segmentation models for the esophagus.

Manual segmentation of tumors and organs-at-risk (OAR) in 3D imaging for radiation-therapy planning is time-consuming and subject to variation between different observers. Artificial intelligence (AI) can assist with segmentation, but challenges exist in ensuring high-quality segmentation, especially for small, variable structures, such as the esophagus. We investigated the effect of variation in segmentation quality and style of physicians for training deep-learning models for esophagus segmentation and proposed a new metric, edge roughness, for evaluating/quantifying slice-to-slice inconsistency. This study includes a real-world cohort of 394 patients who each received radiation therapy (mainly for lung cancer). Segmentation of the esophagus was performed by 8 physicians as part of routine clinical care. We evaluated manual segmentation by comparing the length and edge roughness of segmentations among physicians to analyze inconsistencies. We trained eight multiple- and individual-physician segmentation models in total, based on U-Net architectures and residual backbones. We used the volumetric Dice coefficient to measure the performance for each model. We proposed a metric, edge roughness, to quantify the shift of segmentation among adjacent slices by calculating the curvature of edges of the 2D sagittal- and coronal-view projections. The auto-segmentation model trained on multiple physicians (MD1-7) achieved the highest mean Dice of 73.7 ± 14.8%. The individual-physician model (MD7) with the highest edge roughness (mean ± SD: 0.106 ± 0.016) demonstrated significantly lower volumetric Dice for test cases compared with other individual models (MD7: 58.5 ± 15.8%, MD6: 67.1 ± 16.8%, p < 0.001). A multiple-physician model trained after removing the MD7 data resulted in fewer outliers (e.g., Dice ≤ 40%: 4 cases for MD1-6, 7 cases for MD1-7, Ntotal = 394). While we initially detected this pattern in a single clinician, we validated the edge roughness metric across the entire dataset. The model trained with the lowest-quantile edge roughness (MDER-Q1, Ntrain = 62) achieved significantly higher Dice (Ntest = 270) than the model trained with the highest-quantile ones (MDER-Q4, Ntrain = 62) (MDER-Q1: 67.8 ± 14.8%, MDER-Q4: 62.8 ± 15.7%, p < 0.001). This study demonstrates that there is significant variation in style and quality in manual segmentations in clinical care, and that training AI auto-segmentation algorithms from real-world, clinical datasets may result in unexpectedly under-performing algorithms with the inclusion of outliers. Importantly, this study provides a novel evaluation metric, edge roughness, to quantify physician variation in segmentation which will allow developers to filter clinical training data to optimize model performance.

Lung sparing in MR-guided non-adaptive SBRT treatment of peripheral lung tumors.

Objective.We aim to: (1) quantify the benefits of lung sparing using non-adaptive magnetic resonance guided stereotactic body radiotherapy (MRgSBRT) with advanced motion management for peripheral lung cancers compared to conventional x-ray guided SBRT (ConvSBRT); (2) establish a practical decision-making guidance metric to assist a clinician in selecting the appropriate treatment modality.Approach.Eleven patients with peripheral lung cancer who underwent breath-hold, gated MRgSBRT on an MR-guided linear accelerator (MR linac) were studied. Four-dimensional computed tomography (4DCT)-based retrospective planning using an internal target volume (ITV) was performed to simulate ConvSBRT, which were evaluated against the original MRgSBRT plans. Metrics analyzed included planning target volume (PTV) coverage, various lung metrics and the generalized equivalent unform dose (gEUD). A dosimetric predictor for achievable lung metrics was derived to assist future patient triage across modalities.Main results.PTV coverage was high (median V100% > 98%) and comparable for both modalities. MRgSBRT had significantly lower lung doses as measured by V20 (median 3.2% versus 4.2%), mean lung dose (median 3.3 Gy versus 3.8 Gy) and gEUD. Breath-hold, gated MRgSBRT resulted in an average reduction of 47% in PTV volume and an average increase of 19% in lung volume. Strong correlation existed between lung metrics and the ratio of PTV to lung volumes (RPTV/Lungs) for both modalities, indicating that RPTV/Lungsmay serve as a good predictor for achievable lung metrics without the need for pre-planning. A threshold value of RPTV/Lungs< 0.035 is suggested to achieve V20 < 10% using ConvSBRT. MRgSBRT should otherwise be considered if the threshold cannot be met.Significance.The benefits of lung sparing using MRgSBRT were quantified for peripheral lung tumors; RPTV/Lungswas found to be an effective predictor for achievable lung metrics across modalities. RPTV/Lungscan assist a clinician in selecting the appropriate modality without the need for labor-intensive pre-planning, which has significant practical benefit for a busy clinic.

Exploring published and novel pre-treatment CT and PET radiomics to stratify risk of progression among early-stage non-small cell lung cancer patients treated with stereotactic radiation.

PURPOSE: Disease progression after definitive stereotactic body radiation therapy (SBRT) for early-stage non-small cell lung cancer (NSCLC) occurs in 20-40% of patients. Here, we explored published and novel pre-treatment CT and PET radiomics features to identify patients at risk of progression. MATERIALS/METHODS: Published CT and PET features were identified and explored along with 15 other CT and PET features in 408 consecutively treated early-stage NSCLC patients having CT and PET < 3 months pre-SBRT (training/set-aside validation subsets: n = 286/122). Features were associated with progression-free survival (PFS) using bootstrapped Cox regression (Bonferroni-corrected univariate predictor: p ≤ 0.002) and only non-strongly correlated predictors were retained (|Rs|<0.70) in forward-stepwise multivariate analysis. RESULTS: Tumor diameter and SUVmax were the two most frequently reported features associated with progression/survival (in 6/20 and 10/20 identified studies). These two features and 12 of the 15 additional features (CT: 6; PET: 6) were candidate PFS predictors. A re-fitted model including diameter and SUVmax presented with the best performance (c-index: 0.78; log-rank p-value < 0.0001). A model built with the two best additional features (CTspiculation1 and SUVentropy) had a c-index of 0.75 (log-rank p-value < 0.0001). CONCLUSIONS: A re-fitted pre-treatment model using the two most frequently published features - tumor diameter and SUVmax - successfully stratified early-stage NSCLC patients by PFS after receiving SBRT.

Cabozantinib Plus Nivolumab in Patients with Non-Clear Cell Renal Cell Carcinoma: Updated Results from a Phase 2 Trial.

Treatment options are limited for patients with non-clear cell renal cell carcinoma (nccRCC). Patients with nccRCC experienced a favorable objective response rate (ORR) in a phase 2 trial of cabozantinib plus nivolumab. We now report updated efficacy and safety results at median follow-up of 34 mo for patients with papillary, unclassified, or translocation-associated RCC. Cabozantinib and nivolumab were administered at standard doses to patients with metastatic nccRCC that had progressed on zero or one line of systemic therapy. The primary endpoint was the ORR according to Response Evaluation Criteria in Solid Tumors v1.1. Secondary endpoints included progression-free survival (PFS), overall survival (OS), and adverse events. Forty patients were treated. At median follow-up of 34 mo for survivors, the ORR was 48% (95% confidence interval [CI] 31.5-63.9%). Median PFS was 13 mo (95% CI 7-16); the 12-mo and 24-mo PFS rates were 51% (95% CI 34-65%) and 23% (95% CI 11-37%), respectively. Median OS was 28 mo (95% CI 23-43); the 18-mo and 36-mo OS rates were 70% (95% CI 53-82%) and 44% (95% CI 28-60%), respectively. No new safety signals were seen with cabozantinib and nivolumab. This extended follow-up analysis demonstrates promising efficacy, and highlights the potential for sustained responses with cabozantinib plus nivolumab in patients with metastatic nccRCC. PATIENT SUMMARY: We evaluated outcomes for patients with metastatic kidney cancer of the non-clear cell (NCC) type who were treated with cabozantinib + nivolumab. We found that 48% of the patients responded to the treatment, and there were no unexpected side effects. Among patients who responded to the treatment, the response lasted for a median of 17 months. We conclude that cabozantinib + nivolumab is a safe and effective treatment for NCC kidney cancer.

'Ageing well': Discursive constructions of ageing and health in the public reach of a national longitudinal study on ageing.

Established in 2006, the Irish Longitudinal Study on Ageing (TILDA) investigates the health, economic and social circumstances of a nationally-representative sample of people aged fifty years and older in a series of biennial data collection waves. Irish newspapers have been reporting the results of TILDA for over a decade and a half, and their texts represent reports of scientific research distilled through the pen of journalists. In their totality, their texts constitute a public discourse on ageing and health. Using critical discourse analysis, we examined the discourse within the texts of a purposive sample of two national daily newspapers. As sites of public discourse, newspapers reflect social life and are influential in forming and legitimating public attitudes. Like other sites of discourse, their language-in-use is contextually located, is rarely neutral and may employ strategies to discursively construct, sustain and privilege particular social identities, including ageing identities. Discursively constructed as 'ageing well', our analysis of newspaper texts revealed a discernible meta-discourse on ageing and health in which ageing was framed as a life course stage that may be cultivated, diligently self-nurtured and exploited for its positive aspects. When considered in light of literature on health and social inequalities, the consequences of this broadly positive ageing discourse can, somewhat perversely, frame older adults in unintended negative ways, including homogenising them and attributing to them capacities for ageing well that they may not possess. Discursively constructing older adults as a social and economic resource can also impose unrealistic expectations on them and may legitimise exploitation and demonstrate how normative ideologies of ageism and ableism are conveyed through legitimising language. Despite these potentially unintended consequences, the available media resources associated with TILDA may represent one of the most important contributions of the study, in terms of informing positive public attitudes towards ageing.

A "turn-on" fluorescent sensor for methylglyoxal.

Methylglyoxal (MGO), a dicarbonyl metabolite produced by all living cells, has been associated with a number of human diseases. However, studies of the role(s) MGO plays biologically have been handicapped by a lack of direct methods for its monitoring and detection. To address this limitation, we have developed a fluorescent sensor (methyl diaminobenzene-BODIPY, or "MBo") that can detect MGO under physiological conditions. We show that MBo is selective for MGO over other biologically relevant dicarbonyls and is suitable for detecting MGO in complex environments, including that of living cells. In addition, we demonstrate MBo's utility in estimating plasma concentrations of MGO. The results reported herein have the potential to advance both clinical and basic science research and practice.

Radiotherapy Dose in Patients Receiving Immunotherapy.

There is significant rationale for combining radiation therapy (RT) and immuno-oncology (IO) agents, but the optimal radiation parameters are unknown. This review summarizes key trials in the RT and IO space with a focus on RT dose. Very low RT doses solely modulate the tumor immune microenvironment, intermediate doses both modulate the tumor immune microenvironment and kill some fraction of tumor cells, and ablative doses eliminate the majority of target tumor cells and also possess immunomodulatory effects. Ablative RT doses may have high toxicity if targets are adjacent to radiosensitive normal organs. The majority of completed trials have been conducted in the setting of metastatic disease and direct RT to a single lesion with the goal of generating systemic antitumor immunity termed the abscopal effect. Unfortunately, reliable generation of an abscopal effect has proved elusive over a range of radiation doses. Newer trials are exploring the effects of delivering RT to all or most sites of metastatic disease, with dose personalization based on the number and location of lesions. Additional directions include testing RT and IO in earlier stages of disease, sometimes in further combination with chemotherapy and surgery, where lower doses of RT may still contribute substantially to pathologic responses.

Adjuvant therapy options in renal cell carcinoma - targeting the metastatic cascade.

Localized renal cell carcinoma (RCC) is primarily managed with nephrectomy, which is performed with curative intent. However, disease recurs in ~20% of patients. Treatment with adjuvant therapies is used after surgery with the intention of curing additional patients by disrupting the establishment, maturation or survival of micrometastases, processes collectively referred to as the metastatic cascade. Immune checkpoint inhibitors and vascular endothelial growth factor receptor (VEGFR)-targeting tyrosine kinase inhibitors (TKIs) have shown efficacy in the treatment of metastatic RCC, increasing the interest in the utility of these agents in the adjuvant setting. Pembrolizumab, an inhibitor of the immune checkpoint PD1, is now approved by the FDA and is under review by European regulatory agencies for the adjuvant treatment of patients with localized resected clear cell RCC based on the results of the KEYNOTE-564 trial. However, the optimal use of immunotherapy and VEGFR-targeting TKIs for adjuvant treatment of RCC is not completely understood. These agents disrupt the metastatic cascade at multiple steps, providing biological rationale for further investigating the applications of these therapeutics in the adjuvant setting. Clinical trials to evaluate adjuvant therapeutics in RCC are ongoing, and clinical considerations must guide the practical use of immunotherapy and TKI agents for the adjuvant treatment of localized resected RCC.