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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
Oncological outcomes of deferred systemic therapy for patients with metastatic renal cell carcinoma: A systematic
Ichiro Tsuboi1, Pawel Rajwa2, Marcin Miszczyk3
1Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Department of Urology, Shimane University Faculty of Medicine, Shimane, Japan; Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Background And Objective:
While some patients with metastatic renal cell carcinoma (mRCC) may experience an indolent disease progression and could benefit from deferred systemic therapy (ST), including active surveillance (AS) or metastasis-directed therapy (MDT), the evidence on its oncological efficacy and safety are still not well-established. We aimed to provide an overview of the available evidence on oncological outcomes of patients with mRCC undergoing deferred ST.
Methods:
A systematic review of the literature was conducted in August 2024 using the PubMed, Scopus, and Embase databases to identify prospective and retrospective studies evaluating AS or deferred ST for patients with mRCC (PROSPERO ID: CRD42024579021). The co-primary outcomes were ST-free survival (ST-FS) and overall survival (OS). A random-effects model was used for quantitative analysis.
Key Findings And Limitations:
We identified 15 eligible studies including 2,912 patients. Of these, 4 were prospective (n = 589 patients) and 11 were retrospective (n = 2,323 patients). The estimated 1-, 2-, 3-, 4-, and 5-year ST-FS rates (n = 1,070) were 74%, 54%, 49%, 43%, and 37%, respectively. The estimated 1-, 2-, 3-, 4-, and 5-year OS rates (n = 2,872) were 96%, 89%, 80%, 71%, and 69%, respectively. Key limitations at a study-level included selection bias, unmeasured confounding, and variability across deferred ST/AS protocols, including the indications for metastasis-directed therapy. Moreover, most studies used tyrosine kinase inhibitors as ST. The proportion of patients receiving MDT, including metastasectomy or stereotactic body radiation therapy, ranged from 14 to 100%.
Conclusions And Clinical Implications:
Deferring ST by AS or MDT was associated with favorable oncological outcomes in carefully-selected patients with mRCC, highlighting the potential value of this approach in the contemporary multidisciplinary management of mRCC. Considering the limitations of available evidence and the lack of data on the oncological efficacy and safety of deferred ST for mRCC in the immune-oncology era, our review calls for further research in this field.
Insights
Deferring systemic therapy (ST) with active surveillance (AS) or metastasis-directed therapy (MDT) shows favorable outcomes for carefully selected metastatic renal cell carcinoma (mRCC) patients. Further research is needed, especially in the immune-oncology era.
Area of Science:
- Oncology
- Renal Cell Carcinoma Research
- Systemic Therapy
Background:
- Metastatic renal cell carcinoma (mRCC) can exhibit indolent progression in some patients.
- Deferred systemic therapy (ST), including active surveillance (AS) or metastasis-directed therapy (MDT), may benefit these patients.
- Evidence on the oncological efficacy and safety of deferred ST in mRCC is limited.
Purpose of the Study:
- To provide an overview of the available evidence on oncological outcomes for mRCC patients undergoing deferred ST.
- To evaluate the efficacy and safety of AS or MDT as alternatives to immediate systemic therapy.
Main Methods:
- Systematic literature review conducted in August 2024 using PubMed, Scopus, and Embase.
- Inclusion of prospective and retrospective studies evaluating AS or deferred ST for mRCC.
- Co-primary outcomes: ST-free survival (ST-FS) and overall survival (OS); random-effects model used for analysis.
Main Results:
- 15 studies with 2,912 patients were included; 4 prospective and 11 retrospective.
- Estimated 5-year ST-FS rate was 37% and 5-year OS rate was 69%.
- Limitations include selection bias, confounding, and variability in deferred ST/AS protocols; most studies used tyrosine kinase inhibitors.
Conclusions:
- Deferring ST via AS or MDT is associated with favorable oncological outcomes in selected mRCC patients.
- This approach shows potential value in the multidisciplinary management of mRCC.
- Further research is crucial, particularly regarding deferred ST efficacy and safety in the immune-oncology era.
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