Effectiveness of Immune Checkpoint Inhibitors in Reducing Venous Tumor Thrombus in RCC
Overview
This retrospective multicentric European study evaluated the efficacy of immune checkpoint inhibitors (ICIs) in patients with locally advanced or metastatic renal cell carcinoma (RCC) presenting with venous tumor thrombus (VTT). Among 44 patients treated with ICI-based regimens, a significant proportion showed objective responses in both primary tumors and VTT, highlighting the potential of ICIs to reduce thrombus burden and facilitate surgical management.
Background
Renal cell carcinoma (RCC) is notable for its extension into the venous system, termed venous tumor thrombus (VTT), which complicates surgical treatment and worsens prognosis. VTT occurs in 4 to 10% of localized RCC cases and is associated with higher morbidity and mortality, especially when involving the inferior vena cava. Immune checkpoint inhibitors (ICIs), alone or combined with other agents, have improved outcomes in metastatic RCC, but data on their efficacy specifically against VTT remain limited. This study aimed to assess the response of VTT to ICI-based therapies in a real-world metastatic setting.
Data Highlights
Characteristic
Value
Number of patients
44
Median age (range)
69 (37–88) years
Metastatic disease at diagnosis
38 (86%)
IMDC risk score (Intermediate/Poor)
52% / 48%
Histology (Clear cell / Sarcomatoid)
91% / 7%
First-line ICI-based therapy
82%
ICI regimens
ICI–ICI: 52%, ICI monotherapy: 30%, ICI–TKI: 18%
Common metastatic sites
Lung (82%), Lymph nodes (59%), Bone (36%), Liver (32%)
Patients undergoing delayed nephrectomy and thrombectomy
6
Key Findings
Among 44 RCC patients with VTT treated with ICIs, 82% received first-line ICI-based therapy.
ICI regimens included dual ICI combinations (52%), ICI monotherapy (30%), and ICI combined with tyrosine kinase inhibitors (18%).
Median VTT diameter at baseline was 22 mm, with thrombus extension ranging from renal vein only (level I) to above the diaphragm (level IV).
Objective response rate (ORR) was assessed by RECIST v1.1 criteria, including specific evaluation of VTT response.
Six patients underwent delayed nephrectomy and thrombectomy after a median of 8.5 months of ICI therapy, indicating potential tumor thrombus reduction facilitating surgery.
Majority of patients had metastatic disease with common sites including lung, lymph nodes, bone, and liver.
Clinical Implications
ICI-based therapies demonstrate promising activity against venous tumor thrombus in RCC, potentially reducing thrombus size and extent, which may facilitate subsequent surgical intervention and reduce morbidity. These findings support the integration of immunotherapy in the management of RCC patients with VTT, especially in metastatic settings where systemic control is critical.
Conclusion
Immune checkpoint inhibitors show efficacy in reducing venous tumor thrombus burden in RCC, offering a valuable systemic treatment option that may improve surgical outcomes and patient prognosis. Further prospective studies are warranted to optimize neoadjuvant strategies and confirm these findings.
References
Chow & Redman 2009 -- Management of renal cell carcinoma with venous tumor thrombus
Albiges et al. 2019 -- Systemic therapy in renal cell carcinoma with venous tumor thrombus
UroCCR 128 Study (2023) -- Effectiveness of Immune Checkpoint Inhibitors in RCC with VTT
by Fabien Moinard-Butot, Jonathan Thouvenin, Pierre Bigot, Nieves Martinez-Chanza, Victor Gaillard, Roberto Luigi Cazzato, Romain Boissier, Gaëlle Margue, Philippe Boudier, Denis Maillet, Marine Gross-Goupil, Jean-Christophe Bernhard, Philippe Barthélémy
This twice-monthly newsletter highlights recently published research where Dana-Farber faculty are listed as first or senior authors. The information is pulled from PubMed and this issue notes papers published from November 16 - 30.
Evaluation of circulating kidney injury marker-1 (KIM-1) as a prognostic and predictive biomarker in advanced renal cell carcinoma (aRCC): Post-hoc analysis of CheckMate 214.
