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A Syngeneic Mouse Model of Metastatic Renal Cell Carcinoma for Quantitative and Longitudinal Assessment of Preclinical Therapies
Published on: April 12, 2017
Current Clinical Practice Guidelines for the Treatment of Renal Cell Carcinoma: A Systematic Review and Critical
Aristotle Bamias1,2, Bernard Escudier3, Cora N Sternberg4
1Department of Clinical Therapeutics, National and Kapodistrian University of Athens, School of Medicine, Alexandra Hospital, Athens, Greece.
Abstract:
The landscape of local and systemic therapy of renal cell carcinoma (RCC) is rapidly changing. The increase in the incidental finding of small renal tumors has increased the application of nephron-sparing procedures, while ten novel agents targeting the vascular endothelial growth factor (VEGF) or the mammalian target of rapamycin pathways, or inhibiting the interaction of the programmed death 1 receptor with its ligand, have been approved since 2006 and have dramatically improved the prognosis of metastatic RCC (mRCC). These rapid developments have resulted in continuous changes in the respective Clinical Practice Guidelines/Expert Recommendations. We conducted a systematic review of the existing guidelines in MEDLINE according to the Preferred Reporting Items for Systematic Review and Meta-Analyses statement, aiming to identify areas of agreement and discrepancy among them and to evaluate the underlying reasons for such discrepancies. Data synthesis identified selection criteria for nonsurgical approaches in renal masses; the role of modern laparoscopic techniques in the context of partial nephrectomy; selection criteria for cytoreductive nephrectomy and metastasectomy in mRCC; systemic therapy of metastatic non-clear-cell renal cancers; and optimal sequence of available agents in mRCC relapsed after anti-VEGF therapy as the major areas of uncertainty. Agreement or uncertainty was not always correlated with the availability of data from phase III randomized controlled trials. Our review suggests that the combination of systematic review and critical evaluation can define practices of wide applicability and areas for future research by identifying areas of agreement and uncertainty among existing guidelines.
Implications For Practice:
Currently, there is uncertainity on the role of surgery in MRCC and on the choice of available guidelines in relapsed RCC. The best practice is individualization of targeted therapies. Systematic review of guidelines can help to identify unmet medical needs and areas of future research.
Insights
Guidelines for renal cell carcinoma (RCC) treatment are rapidly evolving. A systematic review identified key areas of uncertainty in managing localized and metastatic RCC, highlighting the need for further research and individualized therapy selection.
Area of Science:
- Oncology
- Urology
- Clinical Practice Guidelines
Background:
- The management of renal cell carcinoma (RCC) is rapidly evolving due to advances in surgical techniques and systemic therapies.
- Novel agents targeting VEGF, mTOR, and immune checkpoints have improved outcomes for metastatic RCC (mRCC).
- These developments necessitate continuous updates to clinical practice guidelines.
Purpose of the Study:
- To systematically review existing RCC guidelines to identify areas of agreement and discrepancy.
- To evaluate the reasons underlying discrepancies in current guidelines.
- To pinpoint areas of uncertainty for future research and clinical practice.
Main Methods:
- A systematic review of MEDLINE-indexed guidelines was performed according to PRISMA statement.
- Data synthesis focused on identifying consensus and divergence in treatment recommendations.
- Areas of uncertainty were analyzed in relation to available evidence, including phase III randomized controlled trials.
Main Results:
- Key areas of uncertainty include selection criteria for nonsurgical approaches, partial nephrectomy, cytoreductive nephrectomy, metastasectomy in mRCC, systemic therapy for non-clear-cell RCC, and sequencing of therapies post-anti-VEGF treatment.
- Agreement and uncertainty were not consistently correlated with the availability of high-level evidence.
- Individualization of targeted therapies is suggested as current best practice.
Conclusions:
- Systematic review and critical evaluation of guidelines can define broadly applicable practices and identify research priorities.
- Addressing uncertainties in RCC management is crucial for optimizing patient outcomes.
- Further research is needed to refine guidelines for complex scenarios in RCC treatment.
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