Surgical management of renal cell carcinoma.
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ABSTRACT:
SUBMITTER: Krabbe LM
PROVIDER: S-EPMC3930656 | biostudies-other | 2014 Mar
REPOSITORIES: biostudies-other
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Project description:The past decade has seen a rapid proliferation in the number and types of systemic therapies available for renal cell carcinoma. However, surgery remains an integral component of the therapeutic armamentarium for advanced and metastatic kidney cancer. Cytoreductive surgery followed by adjuvant cytokine-based immunotherapy (predominantly high-dose interleukin 2) has largely given way to systemic-targeted therapies. Metastasectomy also has a role in carefully selected patients. Additionally, neoadjuvant systemic therapy may increase the feasibility of resecting the primary tumor, which may be beneficial for patients with locally advanced or metastatic disease. Several prospective trials examining the role of adjuvant therapy are underway. Lastly, the first immune checkpoint inhibitor was approved for metastatic renal cell carcinoma (mRCC) in 2015, providing a new treatment mechanism and new opportunities for combining systemic therapy with surgery. This review discusses current and historical literature regarding the surgical management of patients with advanced and mRCC and explores approaches for optimizing patient selection.
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Project description:The management of metastatic renal cell carcinoma (mRCC) has evolved considerably in the last decade. A number of different systemic molecular targeted agents that have been recently approved have improved the survival of patients with mRCC. This mini-review focuses on the implementation of multi-modality therapy in the management of mRCC and the approved indications of the various available novel agents. These novel agents have expanded our armamentarium and improved clinical outcomes of this challenging disease that has considerable biological heterogeneity and clinical variability.
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Project description:BackgroundThere is few of optimal management guideline in elderly patients with renal cell carcinoma (RCC). To compare the survival outcomes of octogenarian RCC group and younger RCC group after surgery using nationwide multi-institutional database.MethodsA total of 10,068 patients who underwent surgery for RCC were included in the current retrospective, multi-institutional study. A propensity score matching (PSM) analysis was conducted to control other confounding factors in analyzing survival outcomes of octogenarian and younger group RCCs. Kaplan-Meier curve analysis to calculate the survival estimates for cancer-specific survival (CSS) and overall survival (OS), and multivariate Cox-proportional hazard regression analyses to evaluate the significant variables associated with the survival outcomes were also performed.ResultsBoth groups were well-balanced in all baseline characteristics. In a total cohort, Kaplan-Meier survival analysis showed a significantly decreased 5-year and 8-year CSS and OS in the octogenarian group compared with the younger group. However, in a PSM cohort, no significant differences were evident between the two groups in terms of CSS (5-year, 87.3% vs. 87.0%; 8-year, 82.2% vs. 78.9%, respectively, log-rank test, p = 0.964). In addition, age ≥ 80 years (HR, 1.199; 95% CI, 0.497-2.896, p = 0.686) was not a significant prognostic factor of CSS in a PSM cohort.ConclusionsThe octogenarian RCC group after surgery had comparable survival outcomes compared with younger group after PSM analysis. For the life expectancy of octogenarian is getting longer, active treatment is considerable in patients with good performance status.
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Project description:Before 2005, systemic treatment of metastatic renal cell carcinoma (RCC) was limited to a few minimally effective options. Since then, new agents have emerged targeting the vascular endothelial growth factor and mTOR pathways, which has improved outcomes for patients. Options increased even further beginning in 2015 with 3 new agents, including the addition of nivolumab, the first immune checkpoint inhibitor to demonstrate improved survival in RCC. RCC has long been considered a malignancy with immunogenic potential, and nivolumab offers the potential for durable responses in some patients with a generally tolerable toxicity profile. With so many drugs available to clinicians and patients, properly integrating immune checkpoint blockade (ICB) into the treatment paradigm is challenging. Additionally, emerging research with other ICB agents, as well as ongoing trials of combination strategies, is likely to further impact clinical decision-making. This article attempts to provide some context to inform systemic treatment decisions in the current landscape, with a particular emphasis on the role of immunotherapy, outlines the ongoing immunotherapy research in RCC, and discusses how treatment may evolve.
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Project description:Sarcomatoid dedifferentiation is an uncommon feature that can occur in most histological subtypes of renal cell carcinomas (RCCs) and carries a decidedly poor prognosis. Historically, conventional treatments for sarcomatoid RCCs (sRCCs) have shown little efficacy, and median survival is commonly 6-13 months. Despite being first described in 1968, the mechanisms driving sarcomatoid dedifferentiation remain poorly understood, and information and treatment options available to physicians and patients are limited. When diagnosed at an early stage, surgical intervention remains the treatment of choice. However, preoperative identification through routine imaging or biopsy is unreliable and most patients present with advanced disease and systemic symptoms. For these patients, the role of cytoreductive nephrectomy is disputed. The expansion of immunotherapies approved for RCCs has generated a search for biomarkers that might be indicative of treatment response in sRCCs, although a proven effective systemic agent remains elusive. PDL1 expression is increased in sarcomatoid dedifferentiated renal tumours, which suggests that patients with sRCCs could benefit from PD1 and/or PDL1 immune checkpoint blockade therapy. Treatment outcomes for sarcomatoid tumours have remained relatively consistent compared with other RCCs, but further investigation of the tumour-immune cell microenvironment might yield insights into further therapeutic possibilities.
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| S-EPMC4778744 | biostudies-literature
Project description:In recent years, targeted agents have changed the treatment landscape for patients with advanced renal cell carcinoma (RCC), greatly improving treatment outcomes. Several targeted agents are now licensed for the treatment of metastatic RCC (mRCC), and a number of new agents are under investigation. Axitinib, a small molecule indazole derivative is an oral, potent multitargeted tyrosine kinase receptor inhibitor, which selectively inhibits vascular endothelial growth factor receptors (VEGFR)-1, -2, and -3 at subnanomolar concentrations, in vitro. In various nonclinical models, axitinib has demonstrated in vivo target modulation and antiangiogenesis. In pharmacokinetic studies, axitinib administered orally with food at the proposed regimen of 5?mg twice daily continuous daily dosing, is rapidly absorbed, reaching peak concentrations within 2-6 hours. Axitinib is metabolized primarily in the liver via the cytochrome P450 (CYP) system with less than 1% of the administered drug passing unchanged in the urine. The pharmacokinetics of axitinib do not appear to be altered by coadministered chemotherapies, and antacids do not have a clinically significant effect. However, coadministration with CYP3A4 and 1A2 inducers is contraindicated. In addition, proton pump inhibitors reduce the rate of axitinib absorption. Increased axitinib exposure is associated with higher efficacy indicated by decreased tumor perfusion and volume. In three phase II clinical trials in patients with advanced RCC previously treated with cytokines, chemotherapy or targeted agents, axitinib has demonstrated antitumor activity with a favorable non-cumulative toxicity profile. In one study of Western patients with cytokine-refractory mRCC, an objective response rate (ORR) of 44.2% (95% CI 30.5, 58.7) was achieved. The median time to progression was 15.7 months (95% CI 8.4, 23.4) and the median overall survival (OS) was 29.9 months (95% CI 20.3, not estimable). In the second study of patients with sorafenib-refractory mRCC, ORR was 22.6% (95% CI 12.9, 35.0). The median progression-free survival (PFS) was 7.4 months (95% CI 6.7, 11.0) and a median OS of 13.6 months (95% CI 8.4, 18.8) was achieved. Results from the third study in Japanese patients with cytokine-refractory mRCC reported an ORR of 55% and median PFS of 12.9 months (95% CI 9.8, 15.6). In the three studies, the most common adverse events reported were fatigue, hypertension, hand-foot syndrome (HFS), and gastrointestinal toxicity, which were generally manageable with standard medical intervention. Of note, the incidence of HFS and proteinuria in the Japanese study was higher than that reported in the Western study in cytokine-refractory mRCC patients. An observed association between diastolic blood pressure ?90?mmHg and increased efficacy suggests potential use as a prognostic biomarker. However, this requires further investigation. Two randomized phase III clinical trials are ongoing to determine the efficacy of axitinib in patients with mRCC in the first- and second-line setting. These results will help to determine the place of axitinib in the mRCC treatment algorithm.
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Project description:Purpose of reviewThis article reviews recent developments in the use of systemic targeted therapies for the treatment of advanced clear and nonclear cell renal cell carcinoma (RCC). The genetic/molecular basis of each form of RCC is discussed and current treatments and clinical trials are described.Recent findingsThe treatment of advanced RCC continues to be a major challenge for uro-oncologists. The rapid growth in therapeutic options has brought much needed improvements in overall and progression-free survival, although durable complete responses remain elusive. The recent identification of mutations in genes involved in chromatin remodeling will likely lead to the investigation of whether components of this critical process can also be valid therapeutic targets in clear cell RCC. Similarly, efforts to decipher the molecular mechanisms underlying nonclear cell variants of RCC are beginning to engender novel therapeutic strategies directed against these rarer forms of kidney cancer. Despite the availability of multiple treatment options, several challenges remain: selecting the best first-line or subsequent therapy for a given patient, the optimal sequencing of the various agents available, designing trials with appropriate comparison arms and endpoints, and identifying well tolerated and effective drug combinations.SummaryAgents targeting the vascular endothelial growth factor and mammalian target of rapamycin pathways remain the mainstay in the management of metastatic RCC. Ongoing and future studies are expected to facilitate the development of therapeutic regimens that incorporate agents with improved tolerability and enhanced efficacy by continuing to capitalize on the strides made by basic and translational scientists in uncovering the mechanisms underlying the various forms of RCC.
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Project description:Treatment of metastatic renal cell carcinoma (mRCC) has evolved with the development of a variety of systemic agents; however, these therapies alone rarely lead to a complete response. Complete consolidative surgery with surgical metastasectomy has been associated with improved survival outcomes in well-selected patients in previous reports. No randomized control trial exists to determine the effectiveness of metastasectomy. Therefore, reviewing observational studies is important to best determine which patients are most appropriate for metastasectomy for mRCC and if such treatment continues to be effective with the development of new systemic therapies such as immunotherapy. In this narrative review, we discuss the indications for metastasectomies, outcomes, factors associated with improved survival, and special considerations such as location of metastasis, number of metastases, synchronous metastases, and use of systemic therapy. Additionally, alternative treatment options and trials involving metastasectomy will be reviewed.
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Project description:Renal cell carcinoma is a highly malignant cancer that would benefit from non-invasive innovative markers providing early diagnosis and recurrence detection. Circulating tumor cells are a particularly promising marker of tumor invasion that could be used to improve the management of patients with RCC. However, the extensive genetic and immunophenotypic heterogeneity of cells from RCC and their trend to transition to the mesenchymal phenotype when they circulate in blood constitute a challenge for their sensitive and specific detection. This review analyzes published studies targeting CTC in patients with RCC, in the context of the biological, pathological, and molecular complexity of this particular cancer. Although further analytical and clinical studies are needed to pinpoint the most suitable approach for highly sensitive CTC detection in RCC patients, it is clear that this field can bring a relevant guide to clinicians and help to RCC patients. Furthermore, as described, a particular subtype of RCC-the ccRCC-can be used as a model to study the relationship between cytomorphological and genetic cellular markers of malignancy, an important issue for the study of CTC from any type of solid cancer.
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