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Updated: May 4, 2026
A Syngeneic Mouse Model of Metastatic Renal Cell Carcinoma for Quantitative and Longitudinal Assessment of Preclinical Therapies
Published on: April 12, 2017
Differential Tumor Response Patterns and Extent of Necrosis After Immunotherapy Combinations Predict Clinical
Wadih Issa1, Nicolas Sayegh1, Damla Gunenc1
1Division of Hematology and Oncology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Background:
The optimal integration of immunotherapy and surgery in the management of advanced clear cell renal cell carcinoma (ccRCC) remains under investigation. Deferred cytoreductive nephrectomy (dCN) following immune checkpoint inhibitor (IO)-based therapy may provide clinical benefit in selected patients, but radiologic and pathologic predictors of response are not well defined.
Methods:
We conducted a retrospective analysis of patients with advanced or metastatic ccRCC treated with perioperative IO-IO or IO-tyrosine kinase inhibitor (IO-TKI) regimens followed by dCN. Radiographic response, IVC thrombus changes, pathological necrosis, immune-related adverse events, and progression-free survival (PFS) were evaluated.
Results:
A total of 55 patients were eligible and included in this analysis. Regimens with IO-TKI were associated with greater tumor size reduction, higher rates of IVC thrombus downstaging, and increased tumor necrosis compared to IO-IO. Tumor necrosis ≥ 20% and ≥ 80% on final pathology correlated with improved PFS. Immune-related toxicities were more common in patients receiving IO-IO.
Conclusions:
Preoperative IO-TKI combinations are associated with meaningful radiologic and pathologic responses in advanced ccRCC and may be considered when the goal is cytoreduction. Tumor necrosis may serve as a prognostic marker of response. These findings support the ongoing evaluation of dCN in prospective trials and highlight the importance of multidisciplinary patient selection.
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