PT  - JOURNAL ARTICLE
AU  - Labbate, Craig
AU  - Hatogai, Ken
AU  - Werntz, Ryan
AU  - Stadler, Walter M.
AU  - Steinberg, Gary D.
AU  - Eggener, Scott
AU  - Sweis, Randy F.
TI  - Complete response of renal cell carcinoma vena cava tumor thrombus to neoadjuvant immunotherapy
AID  - 10.1186/s40425-019-0546-8
DP  - 2019 Dec 01
TA  - Journal for ImmunoTherapy of Cancer
PG  - 66
VI  - 7
IP  - 1
4099  - http://jitc.bmj.com/content/7/1/66.short
4100  - http://jitc.bmj.com/content/7/1/66.full
SO  - J Immunother Cancer2019 Dec 01; 7
AB  - 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.Abbreviations:CTLA4cytotoxic T-lymphocyte-associated protein 4IMDCInternational Metastatic RCC Database ConsortiumORRoverall response rateOSoverall survivalPD1programmed cell death protein 1PD-L1programmed cell death ligand 1RCCrenal cell carcinomaTKItyrosine kinase inhibitor