Treatment Of Kidney Cancer Research Articles

Immunotherapy and targeted-therapy combinations mark a new era of kidney cancer treatment.

Results from the latest phase 3 clinical trial testing combinations of immunotherapy and tyrosine-kinase inhibitors for advanced kidney cancer improve standard first-line treatment options for patients.

Patient-reported Quality of Life following Stereotactic Body Radiation Therapy for Primary Kidney Cancer – Results from a Prospective Cohort Study

AimsWe report on the first prospective series of patient-reported quality of life (QoL) following stereotactic body radiation therapy (SBRT) for primary kidney cancer. Materials and methodsPatients were treated on a multi-institutional prospective cohort study with 30–42 Gy SBRT in three or five fractions. QoL assessments were carried out using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-15 Palliative (EORTC-QLQ-C15-PAL), the Functional Assessment of Cancer Therapy-Kidney Symptom Index-19 (FACT FKSI-19) and the EuroQol-5D-3L tools at baseline, 1 week, and 1, 3 and 6 months post-treatment. QoL over time was analysed using linear mixed modelling, pairwise and anchor-based analyses. ResultsTwenty-eight patients were included. No significant reduction in any QoL metric was observed on repeated measures. However, a trend to reduced EORTC global QoL and fatigue was observed at 1 week, with improvement over time in other symptom scores such as pain, appetite and nausea. On pairwise analysis, there were statistically significant reductions in global QoL at 1 week (with subsequent recovery) and dyspnoea at 6 months post-SBRT. Trends to improved pain, appetite and nausea were observed following SBRT. Less than half of patients reported stable or better EORTC global QoL at 1 week. For all other QoL and symptom scales, most patients had reported stable or better scores at all times, with a slight proportional improvement in emotional functioning, nausea, fatigue, pain and appetite, and a slight worsening of physical functioning and dyspnoea over time. ConclusionsSBRT results in well-preserved QoL in the weeks to months following treatment for primary kidney cancer.

Gene expression profiling (GEP) to identify metabolic gene signature predictive of recurrence after surgery in stage III clear-cell renal cell carcinoma (ccRCC).

355 Background: Management of patients with localized or locally advanced renal cell cancer (RCC) involves surgical resection. However, 20-40% of all localized kidney cancer patients experience a recurrence. Adjuvant treatment in high-risk kidney cancer has not proven to successfully improve overall survival (OS) and the only drug approved so far in this setting is vascular endothelial growth factor (VEGF) inhibitor, sunitinib. As multiple trials are evaluating drugs including immune checkpoint inhibitors in patients with high risk localized clear cell RCC, there is an urgent need to identify biomarkers to help with therapeutic decisions as well as for risk stratification. Here we present analysis pertaining to genes involved in metabolic reprogramming in kidney cancer. Methods: A deep transcriptomic analysis of patients with stage III ccRCC in the TCGA KIRC Firehose Legacy cohort was undertaken. Caucasian males with stage III ccRCC in the TCGA cohort for whom recurrence data was available with a minimum follow-up of 2 years were identified for the analysis. Expression profiles of differentially expressed genes were clustered using the Bayesian infinite mixture model and samples clustered using average linkage hierarchical clustering based on pairwise Pearson’s correlations as the measure of similarity. Enrichment analysis of up- and down-regulated genes was performed using logistic regression. R package was used to generate Kaplan-Meier curves and assess statistical significance of differences in overall and disease-free survival using log-rank test. Results: The cohort evaluated for this study included Caucasian male patients that remained disease free for at least 24 months after surgery (n = 22) and patients whose cancer recurred within 24 months (n = 20). We identified metabolic genes, encoding subunits of mitochondrial electron transport chain as well as malate aspartate shuttle (MAS), where loss of coordinated co-expression between these genes identified patients at risk of recurrence after surgery. The gene signature stratified the 42 patients into three subtypes: significantly enriched for a) recurrence (subtype 1), for b) disease free status (subtype 2) and b) intermediate (subtype 3). Work is underway to combine the use of individual gene expression and ratios of gene expression within the signature to optimize prognostic biomarkers for localized ccRCC. Conclusions: In this analysis, we have identified a novel metabolic gene signature which can help identify patients with localized ccRCC at high risk of recurrence after surgery to guide aggressive therapy. These findings require further validation in tumors collected from patients with stage III ccRCC.

Resection of a kidney tumor with superselective targeted balloon-occluded chemoembolization

Objective : to develop a method of laparoscopic resection of a kidney tumor with super selective balloon occlusion of the segmental renal artery and targeted chemoembolization. Another purpose is to estimate the degree of fixation of the chemotherapy drug in the kidney parenchyma. Materials and methods . The study included the results of experiments on 14 laboratory rabbits, who underwent an intra-arterial injection of the coloring substance of Ponceau S and there were determined its concentration in the renal parenchyma after fixation with a hemostatic suture for 8 days after the injection of the marker. Besides, there were included the results of 13 studies of the contrast substance of ultraravist and gadovist concentration in the renal tissue of patients after resection of the neoplasm with intra-arterial injection of the contrast substance into the parenchyma of the operated kidney. Results. The implemented study showed the presence of a high concentration of a substance injected into the renal artery and a hemostatic suture fixed to the wound edges in the kidney tissue for 6-8 days of the postoperative period. Conclusion . Laparoscopic resection of a malignant kidney tumor with a super-selective balloon occlusion of the segmental renal artery, supplemented by the injection of a targeted chemotherapy agent into the renal artery is a highly effective, safe and simple method of surgical treatment of kidney cancer with enhanced anti-relapse protection due to high concentrations of chemotherapy in the resection area.

Cáncer renal

Kidney cancer is the seventh most common neoplasm and is more frequent in males. The exact etiology of this disease is unknown, although its relationship to tobacco and obesity has been established. Two percent are hereditary; they are associated with genetic syndromes such as Von Hippel–Lindau disease. Fifty percent are diagnosed as incidental imaging findings when conducting imaging tests for other reasons. Clear cell renal cell carcinoma is the most frequent histology. It is staged according to the AJCC's TNM staging system and based on a risk evaluation (low, intermediate, or high according to the MSKCC scale). The treatment of localized kidney cancer is eminently surgical and, based on current studies, there is no evidence for adjuvant therapy. Treatment of advanced disease is based on immunotherapy and tyrosine kinase inhibitors (TKI) according to each patient's risk group.

Modern technologies in the diagnosis and treatment of kidney cancer

Renal cell carcinoma (RCC) diagnosis and management have undergone significant shifts in the recent past. MSCT makes it possible to assess not only the prevalence of the tumor process, but also the calyx-pelvic system and vessels; In the past 10 years, due to the technological advancements, laparoscopic nephrectomy has become the popular and effective method of the treatment and a less traumatic alternative to open radical nephrectomy. Laparoscopy may not be used only for removal of the neoplasm, but also for biopsy of the tumor. Over the past years, cryodestruction of neoplasms has become widespread since it is possible to carry out the procedure in real time under the control of ultrasound, CT or MRI. This review aims to highlight recent evidence that has emerged in the diagnosis and management of this complicated oncologic issue.

Histone Methyltransferase G9a Promotes the Development of Renal Cancer through Epigenetic Silencing of Tumor Suppressor Gene SPINK5.

Background Renal cell carcinoma (RCC) accounts for approximately 2–3% of malignant tumors in adults, while clear cell renal cell carcinoma accounts for 70–85% of kidney cancer cases, with an increasing incidence worldwide. G9a is the second histone methyltransferase found in mammals, catalyzing lysine and histone methylation. It regulates gene transcription by catalyzing histone methylation and interacting with transcription factors to alter the tightness of histone-DNA binding. The main purpose of this study is to explore the role and mechanism of G9a in renal cell carcinoma. Methods Firstly, we investigated the expression of G9a in 80 clinical tissues and four cell lines. Then, we explored the effect of G9a-specific inhibitor UNC0638 on proliferation, apoptosis, migration, and invasion of two renal cancer cell lines (786-O, SN12C). In order to study the specific mechanism, G9a knocking down renal cancer cell line was constructed by lentivirus. Finally, we identified the downstream target genes of G9a using ChIP experiments and rescue experiments. Results The results showed that the specific G9a inhibitor UNC0638 significantly inhibited the proliferation, migration, and invasion of kidney cancer in vivo and in vitro; similar results were obtained after knocking down G9a. Meanwhile, we demonstrated that SPINK5 was one of the downstream target genes of G9a through ChIP assay and proved that G9a downregulate the expression of SPINK5 by methylation of H3K9me2. Therefore, targeting G9a might be a new approach to the treatment of kidney cancer. Conclusion G9a was upregulated in renal cancer and could promote the development of renal cancer in vitro and in vivo. Furthermore, we identified SPINK5 as one of the downstream target genes of G9a. Therefore, targeting G9a might be a new treatment for kidney cancer.

MicroRNA Profiling of Morphologically Heterogeneous Clear Cell Renal Cell Carcinoma.

Intratumoral heterogeneity (IH) has been recently described as an important contributor to tumor growth through a branched rather than a linear pattern of tumor evolution for renal cell carcinoma. As to whether the miRNA profiling of the different and heterogeneous areas is the same or not, it is not known. This study analyzed the differences and similarities of the miRNA profiles in histologically distinct regions within several RCC tumors. The observed differences may have great implications for the development of predictive biomarkers and the identification of druggable targets with improvement of combinatorial therapeutic approaches for the effective treatment of kidney cancer, as well as for the identification of circulating malignant cells that can be useful to detect tumor recurrences.

Trends in the surgical management of renal cell carcinoma in a contemporary tertiary care setting.

Background:In the last three eras, the incidence of renal cell carcinoma (RCC) has increased, due to increased radiological studies. The expected 5-year survival rate has become better, associated with the identification of small size renal masses. However, this survival improvement may be secondary to improved surgical techniques and medical therapies for these malignancies.Objectives:The objective was to report the trends of clinical presentation, peri-operative, oncological outcomes, and surgical management trends for RCCs over the period.Methods:After Institutional Review Board approval, a retrospective study for adult patients was conducted, who presented with renal mass and were managed between 2008 and 2019. Variables, including demographics, perioperative and pathological outcomes analyzed using descriptive statistics for continuous variables reported as mean ± standard deviation and categorical variables values compared by Chi-square test. Survival Analysis calculated using the Kaplan-Meier method. The level of significance is set at P-value < 0.05.Results:A total of 588 patients underwent surgical treatment for kidney cancer from January 2008 to January 2019. 237 (40.30%) were females and 351 (59.69%) males. The clinical presentation was higher as an incidental diagnosis of 58.67%. 71.25% of patients were from outside Riyadh city. Pathology was mostly clear cell RCC 61.22% and grade 2 (57.48%). Tumor size, surgery time, and length of hospital stay showed a significant difference between the three periods (both P > 0.05). Robotic surgery performed more than open (P < 0.0001). There was no significant difference in the survival time, when compared to patients by the regions and when compared by the primary tumors (Log-Rank P = 0.4821). Patients from the Riyadh region (median = 54.0) had a significantly higher recurrence time (Log-Rank P < 0.0001).Conclusion:There was a rising trend in the incidence of RCC associated with comorbidities and incidental diagnosis. In our study period we found increase in the trend of minimal invasive approach. The size of the tumor, blood loss and operative time decreases over the period of time. The Robotic assisted nephrectomy approach has become increased over the period of time duration in present study.

Personalized approach to the treatment of metastatic kidney cancer

Objective: Develop a new organizational form of a personalized approach to assign a target therapy to the patients with metastatic nephrocellular cancer concerning its clinical and economic effectiveness.Methods: The data by cancer register of the Primorsky region were used. 446 patients are included in the register, it allowed to estimate clinical-economic effectiveness of the target therapy by studying 88 cases.Results: 5 medicines were used: sunitrib, soraphenib, bevazizumab, everolimus and pazopanib. The control of the progress of the disease and the toxicity covered 44,3% of the patients. The toxicity of the 3–4th levels were registered during the treatment by inhibitors tyrozinkinaz. The target line therapy increased expenditures by 10% and allowed to increase overall survivability to 42 months.Conclusion: An electronic register of the patients provides monitoring, optimizes expenditures and increases the availability of the target therapy up to 19,7%. Sequential therapy is reasonable and provides the increase of the overall patients’ survivability.

Updated European Association of Urology Guidelines on Renal Cell Carcinoma: Nivolumab plus Cabozantinib Joins Immune Checkpoint Inhibition Combination Therapies for Treatment-naïve Metastatic Clear-Cell Renal Cell Carcinoma

Longer follow-up and new trial data from phase 3 randomised controlled trials investigating immune checkpoint blockade (PD-1 or its ligand PD-L1) in advanced clear-cell renal cell carcinoma (RCC) have recently become available. The CheckMate 9ER trial demonstrated an improved progression-free survival (PFS) and overall survival (OS) benefit for the combination of cabozantinib plus nivolumab. A Keynote-426 update demonstrated an ongoing OS benefit for pembrolizumab plus axitinib in the intention-to-treat population, with a PFS benefit seen across all International Metastatic Database Consortium (IMDC) subgroups, while an update of CheckMate 214 confirmed the long-term benefit of ipilimumab plus nivolumab in IMDC intermediate and poor risk patients. The RCC Guidelines Panel continues to recommend these tyrosine kinase inhibitors + immunotherapy (IO) combination across IMDC risk groups in advanced first-line RCC and dual immunotherapy of ipilimumab and nivolumab in IMDC intermediate and poor risk. Patient summaryNew data from trials of immune checkpoint inhibitors for advanced kidney cancer confirm a survival benefit with the combination of cabozantinib plus nivolumab and pembrolizumab plus axitinib and ipilimumab plus nivolumab. These combination therapies are recommended as first-line treatment for advanced kidney cancer.

Abstract PO-177: Cancer burden and survival among transgender patients in the United States

Abstract Background: Cancer burden among transgender patients is currently unknown due to a paucity of available data. Transgender patients face many barriers to healthcare, including discrimination, stigma, and lack of health insurance. Consequently, there may be delays in cancer diagnoses and treatment, resulting in increased cancer mortality among transgender individuals compared to cisgender persons. We sought to examine cancer stage at diagnosis, cancer treatment, and survival among transgender patients compared to cisgender patients in a large national cancer database. Methods: Data from the National Cancer Database (NCDB) included patients diagnosed with cancer between 2003 – 2016. Gender was recorded by physicians in the medical record and we included individuals categorized as “Male”, “Female”, or “Transsexual” (transgender). We examined primary cancers with ≥10 cases occurring in transgender adults aged ≥18 years. Multivariable logistic regression was used to estimate odds ratios (ORs) for advanced stage at diagnosis (stages III and IV versus stages 0, I, and II) and receipt of cancer treatment (e.g. surgery, chemotherapy, radiotherapy, or a combination) comparing transgender and cisgender patients for each cancer site. Hazard ratios (HRs) were estimated with Cox proportional hazards regression to estimate the associations between physician- recorded gender and all-cause survival for each cancer site. Models were adjusted for age at diagnosis, race/ethnicity, insurance status, year of diagnosis, stage at diagnosis, and treatment receipt as applicable. Results: There were 589 transgender cancer patients among the ≥11 million patients in NCDB. Differences in stage at diagnosis, treatment, and survival between transgender and cisgender cancer patients were not broadly observed across cancer sites. However, transgender patients with lung and bronchus cancer may be more likely to be diagnosed at later stages (OR: 1.76, 95% CI: 0.95, 3.28) than cisgender patients. In addition, compared to cisgender patients, transgender patients were less likely to receive treatment for kidney cancer (OR: 0.22, 95% CI: 0.09, 0.55). Finally, survival was worse in transgender patients compared to cisgender patients with non-Hodgkin lymphoma (HR: 2.36; 95% CI: 1.51, 3.70) and urinary bladder cancer (HR: 2.03, 95% CI: 1.31, 3.14). Conclusion: For specific cancers types, transgender patients may be diagnosed at a later stage, be less likely to receive treatment, and have worse survival. However, this study was hampered by the small number of transgender patients and the lack of self-reported gender identity separate from natal sex. Routine collection of gender identity in cancer registries and patient records will allow for improved estimates of cancer incidence, risk, and more meaningful comparisons between transgender and cisgender cancer patients. There is an urgent need to expand our knowledge of cancer burden among transgender individuals as this population grows and ages. Citation Format: Sarah S. Jackson, Xuesong Han, Ziling Mao, Leticia Nogueria, Gita Suneja, Ahmedin Jemal, Meredith S. Shiels. Cancer burden and survival among transgender patients in the United States [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr PO-177.

Nuclear magnetic resonance and surface-assisted laser desorption/ionization mass spectrometry-based metabolome profiling of urine samples from kidney cancer patients

Kidney cancer is one of the most frequently diagnosed cancers of the urinary tract in the world. Despite significant advances in kidney cancer treatment, no urine specific biomarker is currently used to guide therapeutic interventions. In an effort to address this knowledge gap, metabolic profiling of urine samples from 50 patients with kidney cancer and 50 healthy volunteers was undertaken using high-resolution proton nuclear magnetic resonance spectroscopy (1H NMR) and silver-109 nanoparticle enhanced steel target laser desorption/ionization mass spectrometry (109AgNPET LDI MS). Twelve potential urine biomarkers of kidney cancer were identified and quantified using one-dimensional (1D) 1H NMR metabolomics. Seven mass spectral features which differed significantly in abundance (p < 0.05) between kidney cancer patients and healthy volunteers were also detected using 109AgNPET-based laser desorption/ionization mass spectrometry (LDI MS). This work provides a framework to expand biomarker discovery that could be used as useful diagnostic or prognostic of kidney cancer progression

The role of arterial embolisation in the treatment of kidney cancer (literature review)

Although no prospective randomized trials have been performed to date to demonstrate the best clinical and oncological results of embolization, several retrospective studies using arterial embolization for patients with renal cell carcinoma have shown encouraging results. Arterial embolization should be used as a neoadjuvant therapy prior to surgical resection of renal cell carcinoma to reduce the tumor and minimize intraoperative bleeding. Arterial embolization can also be used for palliative purposes in kidney cancer in the treatment of pain and hematuria, which is not amenable to conservative treatment.

Our Experience of Laparoscopic Partial Nephrectomy: Technique and Results

Laparoscopic partial nephrectomy (LPN) is considered an effective modern minimally invasive surgical intervention and is an alternative to open partial nephrectomy (OPN) in the surgical treatment of kidney cancer.The objective: to provide modern evidence of the effectiveness of LPN in the surgical treatment of patients and to describe the further evolution of this minimally invasive technique.Materials and methods. We prospectively analyzed the data of 63 patients who underwent LPN for clinically localized kidney cancer since September 2015 to October2019 in the urology clinic of theNationalMilitaryClinicalHospital «GVKG» of the Ukrainian Ministry of Defense. LPN was performed using anOlympus endoscopic stand. Clinical data were obtained through a prospective analysis of surgical interventions, including intra- and postoperative results and complications. Descriptive statistical analysis and a multivariate logistic regression model were used to predict surgical outcomes.Results. The average age of the patients was 60.7 years; the average preoperative tumor size was33.0 mm. According to the PADUA-scale, 22 (35.0 %) patients were categorized as low difficulty, 23 (36.5 %) to the intermediate difficulty category and 18 (28.5 %) to the high difficulty category. All patients had transperitoneal access. The average surgery time was 156 minutes. The average blood loss was 171 ml. Overall, significant postoperative complications occurred in 2 (3.2 %) patients (Clavien-Dindo &gt;2). We did not find any statistically significant differences between pre- and postoperative level of creatinine (p&lt;0.05). In general, optimal surgical results, including analysis of the surgical margin, degree of ischemia, and level of complications, were achieved in 44 (69.8 %) patients. During an average of 26 months of observation, only two local and two distant metastases were recorded. In the end, using the multivariate logistic regression model, it was revealed that the degree of complexity of the tumor was associated with a greater risk of obtaining a non-optimal surgical result.Conclusions. LPN is an effective minimally invasive alternative to OPN in the treatment of clinically localized renal cell carcinoma. We presented the current experience of the use of LPN in the surgical treatment of kidney cancer. LPN, as it turned out, is an effective and safe minimally invasive operation that provides optimal results in most patients with varying degrees of tumor complexity.

Renal Cancer with Tumor Thrombus of the Inferior Vena Cava and the Right Atrium

ntroduction. A distinctive feature of kidney cancer is a frequent, compared with other tumors, spread of the tumor through the venous collectors (in the renal and inferior vena cava up to the right atrium), along the path of least resistance to invasive growth.The aim of the study was to present a clinical case of radical treatment of kidney cancer involving extensive IVC thrombosis.Materials and methods. The study describes a clinical case of radical treatment of patient M. with kidney cancer involving extensive IVC thrombosis, extending to the right atrium (written informed consent for patient information and images to be published was obtained prior to the study). During preoperative examination, the patient was diagnosed with renal cell carcinoma with non-occlusive hypervascular tumor thrombus of the renal vein, the inferior vena cava and the right atrium based on the findings of ultrasound examination (transabdominal and transthoracic, and transesophageal), multislice computed tomography (MSCT) and magnetic resonance imaging (MRI).Results and discussion. Surgical treatment remains the main method of treatment of renal cell cancer, moreover, the inferior vena cava thrombosis cannot serve as a cause for refusing surgical treatment. The thrombus spreading along the venous collectors is an important factor in determining the tactics of surgical treatment. The length of the tumor thrombus, as well as the degree of its fixation and ingrowth into the vein wall is of great significance for planning surgical techniques and predicting clinical outcomes. Based on various methods of radiological examination, patient M. was diagnosed with cancer of the right kidney, 3 stage T3cNxM0, IVC tumor thrombus, paraneoplastic syndrome (hyperthermia), right-sided nephrectomy with aortocaval lymphadenectomy, thrombectomy from the IVC, vascular isolation of the liver, resection of the IVC, thrombectomy from the right atrium combined with cardiopulmonary bypass.Conclusion. Despite the technical complexity of nephrectomy with thrombectomy from the IVC, especially in the presence of a massive supradiaphragmatic thrombus, these interventions have no alternatives if a radical treatment is to be achieved. Step-by-step support using radiological methods of investigation is an important aspect of patients preparation; this allowing determining the exact volume of the damage and non-invasively assessing clinical outcomes of surgical treatment.

Melatonin as a potential inhibitor of kidney cancer: A survey of the molecular processes.

Studies have shown that despite the decreasing mortality rates of kidney cancer patients, its incidence is increasing. Therefore, a comprehensive re-evaluation of treatment options is necessary to provide appropriate treatments for the increasing number of patients. Moreover, the side effects caused by surgery, which is the main treatment of this disease, may lead to higher morbidity rates. Consequently, new safer approaches must be examined and considered. Major advancements have been made in the field of targeted agents as well as treatments based on immunotherapy since renal cell carcinoma (RCC) does not respond well to chemotherapy. While the therapeutic options for this cancer are increasing, the resulting complexity of selecting the best strategy for treating the patients is daunting. Moreover, each therapeutic option must be evaluated concerning toxicity, cost, and clinical advantages. Several characteristics, which are beneficial for cancer therapies have been attributed to melatonin. For decades, investigations have explored the application of melatonin in the treatment of cancer; insufficient attention has been paid to this molecule at the clinical level. Melatonin plays a role in cancer therapy due to its anti-tumor effects as well as by enhancing the efficacy of other drugs as an adjuvant. In this review, we discuss different roles of melatonin in the treatment of kidney cancer. The studies concerned with the applications of melatonin as an adjuvant in the immunotherapy of patients with kidney cancer are summarized. Also, we highlight the apoptotic and anti-angiogenic effects of melatonin on renal cancer cells which are mediated by different molecules (e.g., HIF-1 and VEGF, ADAMTS1, and MMP-9) and signaling pathways (e.g., P56, P52, and JNK). Furthermore, we take a look into available data on melatonin's ability to reduce the toxicities caused by kidney carcinogens, including ochratoxin A, potassium bromate, and Fe-NTA.

Counterbalancing COVID-19 with Cancer Surveillance and Therapy: A Survey of Patients with Renal Cell Carcinoma

BackgroundWhile providers are challenged with treatment decisions during the coronavirus disease 2019 (COVID-19) crisis, decision making ultimately falls in the hands of patients—at present, their perspective is poorly understood. ObjectiveTo ascertain renal cell carcinoma (RCC) patients’ perspectives on COVID-19 and understand the associated implications for treatment. Design, setting, and participantsAn online survey of RCC patients was conducted from March 22 to March 25, 2020, disseminated through social media and patient networking platforms. The survey comprised 45 items, including baseline demographic, clinicopathologic, and treatment-related information. Patients were additionally queried regarding their anxiety level related to COVID-19 and associated implications for their cancer diagnosis. InterventionAn online survey study. Outcome measurements and statistical analysisDescriptive statistics with graphical outputs were used to characterize survey results. Results and limitationsA total of 539 patients (male:female 39%:58%) from 14 countries responded. Of them, 71% felt that their risk of COVID-19 infection was higher than the general population, and 27% contacted their physician to establish this. Among patients with localized disease (40%), most (42%) had scheduled surveillance scans within 6 wk–65% were unwilling to delay scans. Among patients with metastatic disease, 76% were receiving active therapy. While most patients preferred not to defer therapy (51%), patients receiving immune therapy regimens were less amenable to deferring therapy than those receiving targeted treatment (20% vs 47%). ConclusionsDespite high levels of anxiety surrounding COVID-19, many patients with RCC were inclined to adhere to existing schedules of surveillance (localized disease) and systemic treatment (metastatic disease). Patient summaryThe coronavirus disease 2019 (COVID-19) pandemic has prompted many doctors to develop different treatment strategies for cancer and other chronic conditions. Given the importance of the patient voice in these strategies, we conducted a survey of patients with kidney cancer to determine their treatment preferences. Our survey highlighted that most patients prefer to continue their current strategies of kidney cancer treatment and monitoring.

The Immunotherapy Revolution in Kidney Cancer Treatment: Scientific Rationale and First-Generation Results.

The recent discovery of immune checkpoint inhibitors (ICIs) has revolutionized cancer treatment, including the treatment for renal cell carcinoma (RCC). Following the eras of cytokines and molecularly targeted therapies including vascular endothelial growth factor-directed agents and mammalian target of rapamycin (mTOR) inhibitors, ICIs have become the latest addition to the RCC armamentarium. To understand the scientific rationale behind this revolution in RCC treatment, we have reviewed the fundamental discoveries underlying the transition from old (cytokines) to new (ICIs) immunotherapies. We summarize the pivotal trials (CheckMate 025, CheckMate 214, KEYNOTE-426, JAVELIN Renal 101, IMmotion151) of checkpoint inhibitors for clear cell RCC in various treatment settings. With the availability of many different combination therapies and many more currently under investigation, clear cell RCC treatment is becoming more complex. Patient preferences, disease volumes, and adverse event profiles are essential in determining which option is the best for an individual patient. In the future, biomarkers currently under development could guide these treatment decisions.

ELA/APELA precursor cleaved by furin displays tumor suppressor function in renal cell carcinoma through mTORC1 activation.

Apelin is a well-established mediator of survival and mitogenic signaling through the apelin receptor (Aplnr) and has been implicated in various cancers; however, little is known regarding Elabela (ELA/APELA) signaling, also mediated by Aplnr, and its role and the role of the conversion of its precursor proELA into mature ELA in cancer are unknown. Here, we identified a function of mTORC1 signaling as an essential mediator of ELA that repressed kidney tumor cell growth, migration, and survival. Moreover, sunitinib and ELA showed a synergistic effect in repressing tumor growth and angiogenesis in mice. The use of site-directed mutagenesis and pharmacological experiments provided evidence that the alteration of the cleavage site of proELA by furin induced improved ELA antitumorigenic activity. Finally, a cohort of tumors and public data sets revealed that ELA was only repressed in the main human kidney cancer subtypes, namely clear cell, papillary, and chromophobe renal cell carcinoma. Aplnr was expressed by various kidney cells, whereas ELA was generally expressed by epithelial cells. Collectively, these results showed the tumor-suppressive role of mTORC1 signaling mediated by ELA and established the potential use of ELA or derivatives in kidney cancer treatment.