Complete response of renal cell carcinoma vena cava tumor thrombus to neoadjuvant immunotherapy

Craig Labbate, Ken Hatogai, Ryan Werntz, Walter M Stadler, Gary D Steinberg, Scott Eggener, Randy F Sweis, Craig Labbate, Ken Hatogai, Ryan Werntz, Walter M Stadler, Gary D Steinberg, Scott Eggener, Randy F Sweis

Abstract

Background: Clinically localized renal cell carcinoma is treated primarily with surgery followed by observation or adjuvant sunitinib in selected high-risk patients. The checkpoint inhibitor immunotherapeutic agents nivolumab and ipilimumab have recently shown a survival benefit in the first-line metastatic setting. To date, there have been no reports on the response of localized renal cancer to modern immunotherapy. We report a remarkable response of an advanced tumor thrombus to combined immunotherapy which facilitated curative-intent resection of the non-responding primary renal tumor. We characterized the tumor microenvironment within the responding and non-responding tumors.

Case presentation: A 54-year-old female was diagnosed with a locally advanced clear cell renal cell carcinoma with a level IV tumor thrombus of the vena cava. She was initially deemed unfit for surgical resection due to poor performance status. She underwent neoadjuvant immunotherapy with nivolumab and ipilimumab with a complete response of the vena cava and renal vein tumor thrombus, but had stable disease within her renal mass. She underwent complete surgical resection with negative margins and remains disease-free longer than 1 year after her diagnosis with no further systemic therapy. Notably, pathologic analysis showed a complete response within the vena cava and renal vein, but substantial viable cancer remained in the kidney. Multichannel immunofluorescence was performed and showed marked infiltration of immune cells including CD8+ T cells and Batf3+ dendritic cells in the thrombus, while the residual renal tumor showed a non-T cell-inflamed phenotype.

Conclusions: Preoperative immunotherapy with nivolumab and ipilimumab for locally advanced clear cell renal cancer resulted in a complete response of an extensive vena cava tumor thrombus, which enabled curative-intent resection of a non-responding primary tumor. If validated in larger cohorts, preoperative immunotherapy for locally advanced renal cell carcinoma may ultimately impact surgical planning and long-term prognosis.

Keywords: Ipilimumab; Neoadjuvant immunotherapy; Nephrectomy; Nivolumab; Renal cell carcinoma; Thrombectomy; Tumor thrombus.

Conflict of interest statement

Ethics approval and consent to participate

The patient provided full consent for participation and publication. Ethics approval for a case report is deemed exempt by the University of Chicago IRB.

Consent for publication

Available upon request.

Competing interests

RFS reports consulting and honoraria from Eisai, BMS, AstraZeneca, Puma, Exelixis, and research support from Bayer, BMS, and Eisai. WMS reports consulting and honoraria from Astra-Zeneca, Bayer, BMS, Caremark/CVS, Eisai, Genentech, and Pfizer and research support from Abbvie, Astra-Zeneca, Astellas (Medivation), Bayer, Bristol-Myers-Squibb, Boehringer-Ingelheim, Calithera, Eisai, Exilixis, Genentech (Roche), Johnson & Johnson (Janssen), Merck, Novartis, Pfizer, Seattle Genetics, Tesaro, X4Pharmaceuticals. GDS is scientific advisor and/or investigator for Merck, BMS, AstraZeneca, Roche, Janssen, Ferring, Boston Scientific, Natera, QED Therapeutics, FKD, Fidia, PhotoCure, ColdGenesys, Urogen, Epivax Oncology, Altor Bioscience, BioCancell, Taris Biomedical. CL, KH, RW, and SE declare that they have no competing interests.

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Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Coronal images of tumor thrombus pre- (a) and post- (b) immunotherapy
Fig. 2
Fig. 2
H&E staining of remaining viable renal tumor with a dense neutrophilic infiltrate after immunotherapy
Fig. 3
Fig. 3
Multichannel immunofluorescence of renal mass and tumor thrombus. Representative images of residual tumor in the segmental renal vein that responded to therapy at low power (a) and high power (b) with clusters of co-localized CD8+ T cells and Batf3+ dendritic cells. The primary renal tumor staining pattern is shown at low power (c) and high power (d) featuring far fewer Batf3+ cells and CD8+ T cells

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