Care For Renal Cell Carcinoma Research Articles

Examination of irAE and treatment discontinuation irAE in patients with RCC with T effector phenotype.

4549 Background: The standard of care for renal cell carcinoma (RCC) is physician-choice of dual immunotherapy with ipilimumab/nivolumab (IO/IO) or a combination a VEGF inhibitor with immunotherapy (VEGF/IO). The IMmotion 151 trial identified gene expression signatures that differentiate likelihood of response to IO/IO (cluster 4 and 5 – T effector) versus VEGF/IO (cluster 1 and 2 - Angiogenic). Given that the T effector RNA-seq signature consists of higher expression of genes associated with inflammation, we hypothesized that patients with the T effector phenotype would have higher rates of immune-related adverse events (irAE) on IO-based therapy. Methods: Patients with metastatic RCC treated with systemic IO-based therapy had RNA sequencing completed on the primary tumor or metastatic site. Charts of patients who had a T effector RNA-seq signature were manually curated to identify development of irAE by reading the most recent clinic note and searching ‘steroids’, ‘irAE’, ‘rash’, ‘thyroid’. Hits from searches were investigated by manual chart review. Results: 118 patients underwent RNA sequencing and 105 passed quality control. Nineteen patients (18%) were assigned the T effector phenotype. Of the 17 metastatic patients, twelve of these patients received at least one dose of IO/IO in the first or second line of therapy, five were treated with VEGF/IO Among patients treated with IO/IO, 8 developed any grade irAE (66%; 41% grade 3+), 5 (41%) required steroid treatment, 5 (41%) required hospitalization, and 4 (33%) discontinued treatment due to irAE. Grade 3 toxicities in this group included colitis, adrenal insufficiency, and hypophysitis. Of the 5 patients treated with VEGF/IO, 3 developed any grade irAE (60%; 20% grade 3+), none were treated with steroids, and none were hospitalized. The grade 3 toxicity in this group was adrenal insufficiency. Conclusions: Patients with a T effector RNA-seq signature had higher rates ofirAE than historic controls when treated with IO/IO leading to high rates of steroid use and treatment discontinuation. VEGF/IO-treated patients with the T effector RNA-seq signature had similar rates of irAE to historic controls. The ongoing OPTIC clinical will expand on these results by studying treatment assignment in a prospective manner.

Established and emerging biomarkers of immunotherapy in renal cell carcinoma.

Immunotherapies, such as immune checkpoint inhibitors, have heralded impressive progress for patient care in renal cell carcinoma (RCC). Despite this success, some patients' disease fails to respond, and other patients experience significant side effects. Thus, development of biomarkers is needed to ensure that patients can be selected to maximize benefit from immunotherapies. Improving clinicians' ability to predict which patients will respond to immunotherapy and which are most at risk of adverse events-namely through clinical biomarkers -is indispensable for patient safety and therapeutic efficacy. Accordingly, an evolving suite of therapeutic biomarkers continues to be investigated. This review discusses biomarkers for immunotherapy in RCC, highlighting current practices and emerging innovations, aiming to contribute to improved outcomes for patients with RCC.

P150 - Improving value of care for renal cell carcinoma (RCC) patients; the development of 2 decision aids in The Netherlands

P150 - Improving value of care for renal cell carcinoma (RCC) patients; the development of 2 decision aids in The Netherlands

Enhanced synergy of pacritinib with temsirolimus and sunitinib in preclinical renal cell carcinoma model by targeting JAK2/STAT pathway

Pacritinib is an oral medication that inhibits several kinases including JAK2, FLT3, IRAK and STAT3. It has been recently approved to treat patients with thrombocytopenia and myelofibrosis. Studies are currently exploring the potential use of pacritinib in treating other types of cancer such as leukaemia, breast cancer and prostate cancer. Our study aimed to investigate the effects of pacritinib alone and its combination with standard of care in renal cell carcinoma (RCC). We showed that pacritinib dose-dependently decreased viability of RCC cells, with IC50 at nanomolar or low micromolar concentration rage. Pacritinib inhibited cell proliferation, decreased colony formation, and increased apoptosis. Interestingly, pacritinib exhibited synergistic effects when combined with temsirolimus and sunitinib, but antagonistic effects when combined with doxorubicin, in a panel of RCC cell lines. We also confirmed that the combination of pacritinib with temsirolimus and sunitinib resulted in synergistic effects in RCC mouse models, with complete inhibition of tumour growth throughout the treatment period. Mechanistic studies indicated that the inhibition of JAK2, but not IRAK, was the main contributor to the anti-RCC activity of pacritinib. Our study is the first to demonstrate that pacritinib shows promise as a treatment option for RCC and underscores the therapeutic potential of targeting the JAK2/STAT signalling pathway in RCC.

Predictive value of preoperative neutrophil to lymphocyte ratio and platelet to lymphocyte ratio combined with operating room factors for surgical site infection after laparoscopic radical nephrectomy in renal cell carcinoma patients.

Surgical site infections (SSIs) can pose significant risks to patients undergoing surgical procedures. This study aimed to investigate the risk factors and diagnostic value of neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) for SSIs in patients undergoing laparoscopic radical nephrectomy for renal cell carcinoma. A retrospective analysis of 866 patients at our hospital was conducted between June 2016 and June 2022. The study divided patients into two groups: those with SSIs and those without. General data and operative room-related information were collected. Inclusion and exclusion criteria were clearly defined. Peripheral blood indicators were analysed, and observation indicators were meticulously selected, including surgery time, usage of a laminar flow operating room and intraoperative hypothermia. Statistical analysis was performed using SPSS 25.0 software, including univariate, multivariate analysis and receiver operating characteristic (ROC) curve analysis. Thirty-six out of 866 patients developed SSIs. Statistically significant differences were found for surgery time, usage of non-laminar flow operating rooms and intraoperative hypothermia (p < 0.05). ROC curve analysis showed an AUC of 0.765 (95% CI: 0.636-0.868) for serum NLR and PLR, with optimal cut-off values at NLR 4.8 and PLR 196, indicating moderate to strong discriminative ability for SSIs. The study identified non-laminar flow operating rooms, extended surgery time, and intraoperative hypothermia as significant risk factors for SSIs. Serum NLR and PLR were found valuable as biomarkers for SSIs diagnosis, holding potential for preoperative risk assessment and improved patient safety in renal cell carcinoma care.

Cabozantinib combination therapy for the treatment of solid tumors: a systematic review.

Background:Cabozantinib monotherapy is approved for the treatment of several types of solid tumors. Investigation into the use of cabozantinib combined with other therapies is increasing. To understand the evidence in this area, we performed a systematic review of cabozantinib combination therapy for the treatment of solid tumors in adults.Methods:This study was designed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses, and the protocol was registered with PROSPERO (CRD42020144680). On 9 October 2020, we searched for clinical trials and observational studies of cabozantinib as part of a combination therapy for solid tumors using Embase, MEDLINE, and Cochrane databases, and by screening relevant congress abstracts. Eligible studies reported clinical or safety outcomes, or biomarker data. Randomized and observational studies with a sample size of fewer than 25 and studies of cabozantinib monotherapy were excluded. For each study, quality was assessed using National Institute for Health and Care Excellence methodology, and the study characteristics were described qualitatively. This study was funded by Ipsen.Results:Of 2421 citations identified, 32 articles were included (6 with results from randomized studies, 24 with results from non-randomized phase I or II studies, and 2 with results from both). The most commonly studied tumor types were metastatic urothelial carcinoma/genitourinary tumors and castration-resistant prostate cancer (CRPC). Findings from randomized studies suggested that cabozantinib combined with other therapies may lead to better progression-free survival than some current standards of care in renal cell carcinoma, CRPC, and non-small-cell lung cancer. The most common adverse events were hypertension, diarrhea, and fatigue.Conclusion:This review demonstrates the promising efficacy outcomes of cabozantinib combined with other therapies, and a safety profile similar to cabozantinib alone. However, the findings are limited by the fact that most of the identified studies were reported as congress abstracts only. More evidence from randomized trials is needed to explore cabozantinib as a combination therapy further.

Follow-up of renal cell carcinoma based on stage and initial treatment

Renal cell carcinoma is the third most common tumor of the genitourinary system. Small tumors are increasingly treated by nephron-sparing surgery, focal therapy via cryoablation or radiofrequency ablation and also active surveillance. These treatment options are associated with increased follow-up care. What are the current recommendations on follow-up care for different therapeutic approaches in renal cell carcinoma? We analyzed different biological aspects regarding renal cell carcinoma, diagnostic procedures as well as recommendations of current guidelines (e.g. German S3, EAU AUA). Follow-up of renal cell carcinoma is not well standardized due to the limited amount of data. In general, follow-up should be intensified during the first 3years following initial therapy as well as in patients with increased risk for tumor recurrence. For risk calculation different prognostic models based on clinical parameters have been published. Current recommendations on follow-up care in renal cell carcinoma are based on retrospective studies. Future strategies must include markers and be studied in aprospective manner.

Adjuvant Therapy for Urothelial and Renal Cell Carcinoma

Adjuvant therapy for urothelial and renal cell carcinoma has progressed steadily over the past 30 yr. Level 1 evidence supports a role for both neoadjuvant and adjuvant cisplatin-based chemotherapy for muscle-invasive urothelial carcinoma of the bladder. Recent evidence has also confirmed a benefit from adjuvant therapy in high-grade upper tract urothelial carcinoma. Adjuvant targeted therapy remains controversial and outside the standard of care for renal cell carcinoma, with no proven overall survival benefit. Immune checkpoint blockade is poised to shift the landscape for both urothelial and renal cell carcinoma with the potential for greater efficacy.

Renal Cell Carcinoma: A Case Series with Integrative Treatment

Objective: Renal cell carcinoma (RCC) is a rare and difficult to treat cancer. The case series aimed to observe the effects of medicinal mushrooms and integrative oncology care for renal cell carcinoma. Clinical Features: Patients diagnosed with RCC who were being treated with surgery and chemotherapy and were administered integrative treatment in the form of supplements and medicinal mushrooms and/or combinations of mushrooms. Interventions and outcomes: Integrative care included a combination of supplements and the medicinal mushrooms Ganoderma lucidum, Trametes versicolor, Cordyceps sinensis, Grifola frondosa, and Lentinus edodes in combination or alone, which was initiated following adjuvant care. These patients experienced increased overall survival compared to standard adjuvant treatment alone. Conclusion: Beneficial effects of integrative care were observed in this case series. Disease progression and symptoms related to adjuvant treatment were significantly decreased in these patients after integrative supportive care was initiated and effects persisted through the final observation period. Further controlled studies are needed among larger groups of patients to determine the clinical efficacy of medicinal mushrooms and integrative oncology in the treatment of RCC.

Patterns of care in renal cell carcinoma (RCC): Impact of duration of first-line (1L) treatment on second-line (2L) treatment choice.

e17618 Background: RCC represents a dynamic therapeutic area with multiple classes of treatments and several new agents on the horizon with novel mechanisms of action. Understanding current pattern...

Patterns of care in renal cell carcinoma: Comparison of treatment duration for first-line sunitinib and pazopanib.

e17615 Background: Renal cell carcinoma represents a dynamic therapeutic area with multiple classes of treatments and several new agents on the horizon with novel mechanisms of action. Understandin...

Professional practice gaps and barriers to optimal care of renal cell carcinoma (RCC) among oncologists in the United States.

404 Background: New therapies for advanced RCC have improved patient outcomes while increasing the complexity of care. We sought to quantify practice gaps and barriers to optimal care among oncologists treating patients with RCC at academic and/or community centers in the United States. Methods: In total, 248 oncologists were recruited for a 2-phase (qualitative/quantitative) study. Eligible participants who had fully completed either one of the 2 phases were included in the analyses (n = 169). In the first phase, participants (n = 27) completed a brief online case-based survey and a 45-minute telephone interview on the attitudinal, contextual, and behavioral factors that influenced diagnosis and treatment. Selected interviews were transcribed and analyzed through thematic analysis. In the second phase, participants (n = 142) completed an online survey including case vignettes. Respondents’ answers were compared with optimal answers based on National Comprehensive Cancer Network kidney cancer guidelines (version 1.2013) and evidence-based opinions of 2 RCC experts. Results: Forty-six percent of participants correctly identified all predictors of short survival/poor risk in RCC. Regarding treatment options for a poor-risk patient, 37.5% chose temsirolimus and 11% sunitinib, both felt to be reasonable options. In a scenario focused on dose and treatment modification in a patient with treatment-related hypertension, 34% selected a nonoptimal management option. In a scenario focused on the importance of recognizing clinical symptoms as a component of treatment decision making, 40% of respondents were in agreement with expert- and evidence-supported treatment approach. Detailed results of this analysis will be presented. Conclusions: This study revealed clinically relevant practice performance gaps that affect delivery of care and patient health outcomes. Not recognizing predictors of poor risk or the importance of evaluating clinical symptoms can result in missed opportunities to change treatment strategy, leading to suboptimal outcomes. These results will support design of educational programs and performance improvement interventions.

Contemporary management of renal cell carcinoma (RCC) in Victoria: implications for longer term outcomes and costs

To describe the contemporary patterns of care for renal cell carcinoma (RCC) using a whole of population series from Victoria. Retrospective review of medical records of all patients diagnosed and treated for RCC in Victoria in 2009. Patients were identified via the State-wide Victorian Cancer Registry. Patient demographic characteristics, symptoms, stage, and first-line treatment were assessed. Associations between case residential location (metropolitan or rural) and treatment were examined using multivariate logistic regression after adjusting for age, sex, socioeconomic status, treatment in private or public hospital and comorbidity. Data were obtained for 499 of 577 eligible patients. In all, 413 patients (83%) underwent surgery. Laparoscopic radical nephrectomy (RN) was the most common procedure for Stage I pT1a/pT1b tumours (51.2%); partial nephrectomy (PN) was performed for 27% of Stage I RCC In multivariate analysis, regional patients were less likely to receive PN (odds ratio [OR] 0.39, 95% confidence interval [CI] 0.18-0.85) for Stage I RCC, and less likely to receive systemic therapy for Stage IV RCC (OR 0.06, 95% CI 0.01-0.41). Multidisciplinary team meetings were recorded for only 25% of patients and 3% were enrolled in a clinical trial. Most contemporary patients diagnosed with RCC are still treated with RN, including those with smaller tumours amenable to PN. This may impact future outcomes, including increased risk of chronic kidney disease and its potential financial healthcare burden. Patterns of treatment also appear to differ between metropolitan and regional populations.

Using the Delphi Technique to Improve Clinical Outcomes Through the Development of Quality Indicators in Renal Cell Carcinoma

Optimal quality of care is needed for ideal outcomes. In renal cell carcinoma (RCC), there is a lack of information defining optimal care. This is particularly important in RCC, with increased complexity of care and a need for coordination among providers. The goal of this study was to identify quality indicators (QIs) and measures of quality care across the RCC disease spectrum. A modified Delphi technique was used to select QIs that are relevant and practical to RCC care. This technique involved an expert panel of 13 urologic and medical oncologists who participated in two e-mail questionnaires and an in-person meeting to review and prioritize potential QIs. These potential QIs were identified from a systematic literature review or were suggested by panel members. From 233 literature citations, 34 possible QIs were identified; 24 additional potential QIs were suggested. A final set of 23 QIs was established. These are distributed across the RCC disease spectrum as follows (number of QIs in parentheses): screening (n=1), diagnosis/prognosis (n=3), surgical for localized disease (n=6), surgery for advanced disease (n=3), systemic therapy (n=6), and follow-up (n=2). In addition, two QIs related to survival outcomes (overall and progression-free survival) were selected. A systematic, consensus-based approach was used to determine relevant QIs in RCC care. These 23 QIs will provide a means of evaluating the quality of RCC care in an effort to improve outcomes in patients. The next step will be to establish a means of measuring each QI based on defined or yet-to-be-defined benchmarks.

The 7th American Urological Association and the Japanese Urological Association International Affiliate Society Meeting

The 7th American Urological Association and the Japanese Urological Association International Affiliate Society Meeting

Delayed intervention of sporadic renal masses undergoing active surveillance

Prompt surgical management remains the standard of care for renal cell carcinoma (RCC). Occasionally, it is necessary to postpone or delay surgical treatment. The authors of this report assessed whether delayed intervention following a period of active surveillance altered minimally invasive or nephron-sparing treatment plans, increased the risk of stage progression, and/or decreased recurrence-free survival rates. The authors searched their institutional kidney cancer database to identify small (< or =4 cm in greatest dimension on presentation), enhancing renal masses for which treatment initially was delayed or refused. Clinical, radiographic, and pathologic records were reviewed to determine linear tumor growth kinetics, alterations in treatment plan, stage migration, and cancer-specific outcomes related to delayed intervention. Eighty-seven sporadic, localized, enhancing renal masses were identified in 82 patients who had management postponed for a median of 14 months (mean, 21 months; range, 6-97 months). Median tumor diameter was 2.0 cm on presentation. Treatment in 60 of 87 tumors (69%) was delayed for > or =12 months, and treatment was delayed for > or =24 months in 29 of 87 tumors (33%). Overall, 66 of 87 tumors (76%) underwent nephron-sparing approaches. In addition, 52 of 87 tumors (60%) were treated in a minimally invasive fashion. Pathology confirmed RCC in 73 of 87 treated tumors (84%). Fourteen of 54 tumors (26%) that were treated by surgical extirpation were high-risk tumors, and 3 of 54 tumors (6%) were upstaged on pathologic review. The majority of small, sporadic, clinically localized renal tumors demonstrated slow interval growth. The management of these lesions may be delayed cautiously without limiting or complicating the available treatment options or incurring a high risk of disease progression.

Renal Cell Carcinoma In Patients With Prior Spinal Cord Injury

Introduction: In patients with spinal cord injury (SCI), abdominal diseases such as renal carcinoma are often diagnosed and treated late in their course.Methods: A population-based retrospective review of SCI patients receiving care for renal cell carcinoma (RCC) in all Department of Veterans Affairs (DVA) medical centers was conducted for fiscal years 1988 to 1998.Results: Of 96 patients identified, 57 were evaluable and 27 met study criteria. The mean patient age was 59 (range, 41–79 years). The mean time between SCI and treatment for RCC was 25 years (range, 1- 51 years). All patients were men; 22/ 27 (81 %) had 1 or more comorbid conditions. RCC was an incidental finding on surveillance imaging studies in 81 % (22/27) of the patients. All 27 patients were treated surgically, 74% (20/27) by radical nephrectomy and 26% (7/27) by partial nephrectomy. All tumors were renal cell adenocarcinomas. Pathological staging by the tumor, nodes, and metastasis system was possible in 25; 92% (23/25) of tumors were stage I and 8% (2/25) were stage II. Postoperative morbidity occurred in 56% (15/27), and death occurred in 7% (2/27).Conclusion: In SCI patients in the DVA system, diagnosis of RCC is usually the result of an incidental finding on surveillance imaging. Tumors are diagnosed at early stages and partial nephrectomy is often feasible. Many of the postoperative complications are related to the SCI, and may be preventable.J Spinal Cord Med. 2001 ;24:251–256

Renal tumor ablation: energy-based technologies.

Radical nephrectomy has been the standard of care for renal cell carcinoma since its description by Robson [44]. Within the past decade, partial nephrectomy has become established as an oncologically viable nephron-sparing alternative in select patients with a kidney tumor in the setting of actual or potential compromise of global nephron mass [40] or patients with a small (4 cm) tumor with a normal contralateral kidney [30]. However, although both procedures achieve excellent local cancer control, they are associated with considerable post-operative morbidity and prolonged recovery. Recent advances in urologic surgery have provided some attractive alternatives to open surgical radical or partial nephrectomy. Laparoscopic radical nephrectomy efficaciously retrieves an oncologically adequate surgical specimen while dramatically decreasing patient morbidity [23], and has been shown to be better tolerated in high-risk patients, including the obese [18] and the elderly [26]. As regards minimally invasive nephron-sparing procedures, laparoscopic partial nephrectomy has been performed in a few cases, although its technical refinement and standardization remain to be achieved. As an even less invasive alternative to laparoscopic partial nephrectomy, recent investigations have focused on the laparoscopic or percutaneous delivery of various energy forms in a realtime monitored manner, to achieve targeted destruction of renal parenchyma. Initial investigations into alternative treatments for solid organ tumors began with the prostate and the liver, due to the severe morbidity associated with surgery on the former, and the frequent unresectability of tumors in the latter. Subsequently, attention was turned towards the possible utility of these modalities with renal tumors. The unique anatomic location of the kidney allows it to be isolated easily during laparoscopic procedures. Furthermore, the kidney can be imaged well throughout any application. As a result, alternative ablative treatments for renal tumors have progressed from animal studies to clinical trials. Herein, we will discuss a variety of current alternative renal tumor ablation techniques: cryoablation (laparoscopic and percutaneous approaches), radiofrequency ablation (wet and dry), microwave thermotherapy, intracavitary photon radiation, and high intensity focused ultrasound (HIFU).