Phase II Study of Neoadjuvant Nivolumab in Patients with Locally Advanced Clear Cell Renal Cell Carcinoma Undergoing Nephrectomy.

Immune checkpoint inhibitor therapy improves survival in patients with metastatic renal cell carcinoma (RCC) but has not been studied well preoperatively in patients with localized disease undergoing nephrectomy. We conducted a single-center study to evaluate the safety and feasibility of neoadjuvant nivolumab in patients undergoing nephrectomy for localized RCC. Eligible patients had a >20% risk of recurrence, as estimated by a preoperative nomogram. Patients received nivolumab every 2 wk for four treatments prior to surgery. The primary endpoints were feasibility, defined as completing at least three treatments without significant surgical delay, and safety, defined as the rate of surgical complications. Treatment effects were assessed by radiomics and immunohistochemistry. A total of 18 patients (11 men; median age 60 yr) with clear cell RCC were enrolled. All received at least one dose of nivolumab and proceeded to nephrectomy without delay; 16/18 patients completed all four doses. Two patients discontinued nivolumab for immune-related adverse events, and four had surgical complications as per the Clavien-Dindo classification. Integrated pathology plus radiomic analysis demonstrated an association between post-treatment immune infiltration and low entropy apparent diffusion coefficient on magnetic resonance imaging. Nivolumab prior to nephrectomy was safe and feasible, without significant surgical delays and with an expected rate of immune-related adverse events. PATIENT SUMMARY: We evaluated the outcomes for patients with localized kidney cancer who received immunotherapy prior to surgery to remove their kidney tumor. In a small group of patients who had cancer confined to the kidney, this approach appeared safe and feasible.

European urology. 2022 Feb 16 [Epub ahead of print]

Maria I Carlo, Kyrollis Attalla, Yousef Mazaheri, Sounak Gupta, Onur Yildirim, Samuel J Murray, Devyn T Coskey, Ritesh Kotecha, Chung-Han Lee, Darren R Feldman, Paul Russo, Sujata Patil, Robert J Motzer, Jonathan A Coleman, Jeremy C Durack, Ying-Bei Chen, Oguz Akin, A Ari Hakimi, Martin H Voss

Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Department of Pathology, Mayo Clinic, Rochester, MN, USA., Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH, USA., Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA. Electronic address: ., Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA. Electronic address: .