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Updated: Feb 15, 2026
A Syngeneic Mouse Model of Metastatic Renal Cell Carcinoma for Quantitative and Longitudinal Assessment of Preclinical Therapies
Published on: April 12, 2017
Overview of Current and Future Adjuvant Therapy for High-Risk Localized Renal Cell Carcinoma
Lakshminarayanan Nandagopal1, Gurudatta Naik1, Guru Sonpavde2
1Department of Medicine, Section of Hematology-Oncology, University of Alabama at Birmingham (UAB), Birmingham, AL, USA.
Opinion Statement:
High-risk localized renal cell carcinoma represents a therapeutic challenge with high recurrence rates and poor survival with nephrectomy alone. Multiple agents targeting angiogenic and immunologic pathways have demonstrated remarkable efficacy in the metastatic setting but have failed to replicate similar successes in localized disease. Study results with adjuvant anti-angiogenic therapies may have been compromised by the high incidence of treatment discontinuations or dosage reductions secondary to intolerable side effects. Improving patient selection could play a major role in improving outcomes. Multiple models exist to predict survival but require improved accuracy in identifying recurrence to justify exposing patients to therapies that could significantly impair quality of life. Further understanding of pathological and molecular mechanisms of recurrence is required. Novel tools like gene recurrence scores are emerging to improve prognostication for patient selection. Immunotherapeutic approaches using check point inhibition have the potential to achieve sustained remissions with a significantly improved toxicity profile. Amplifying the immune response with a combination of neoadjuvant and adjuvant therapy to exploit the larger antigenic burden prior to nephrectomy has the biologic potential for making significant improvements in efficacy.
Insights
High-risk localized kidney cancer is hard to treat. New strategies like immunotherapy and gene recurrence scores may improve patient selection and outcomes, potentially reducing recurrence after nephrectomy.
Area of Science:
- Oncology
- Nephrology
Background:
- High-risk localized renal cell carcinoma (RCC) presents a significant therapeutic challenge, with high recurrence rates and poor survival following nephrectomy alone.
- While anti-angiogenic and immunologic agents show efficacy in metastatic RCC, their success in localized disease is limited, partly due to side effects causing treatment discontinuation.
Purpose of the Study:
- To explore strategies for improving outcomes in high-risk localized renal cell carcinoma.
- To address the limitations of current adjuvant therapies and survival prediction models in localized RCC.
- To investigate the potential of novel prognostic tools and immunotherapeutic approaches.
Main Methods:
- Review of current therapeutic challenges and treatment outcomes in localized renal cell carcinoma.
- Analysis of the efficacy and toxicity profiles of adjuvant anti-angiogenic therapies.
- Exploration of emerging prognostic tools, including gene recurrence scores.
- Evaluation of immunotherapeutic strategies, such as checkpoint inhibition and neoadjuvant/adjuvant combinations.
Main Results:
- Adjuvant anti-angiogenic therapies have shown limited success in localized RCC, often due to side effects.
- Existing survival prediction models lack the accuracy needed for optimal patient selection.
- Gene recurrence scores offer potential for improved prognostication and patient selection.
- Immunotherapy, particularly checkpoint inhibition, shows promise for sustained remissions with a better toxicity profile.
Conclusions:
- Improved patient selection is crucial for enhancing treatment outcomes in high-risk localized RCC.
- Novel prognostic tools like gene recurrence scores are needed to guide therapy decisions.
- Immunotherapeutic approaches, potentially combined with neoadjuvant and adjuvant strategies, hold significant promise for improving efficacy and reducing recurrence in localized RCC.
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