The future of perioperative therapy in advanced renal cell carcinoma: how can we PROSPER?

Patients with high-risk renal cell carcinoma (RCC) experience high rates of recurrence despite definitive surgical resection. Recent trials of adjuvant tyrosine kinase inhibitor therapy have provided conflicting efficacy results at the cost of significant adverse events. PD-1 blockade via monoclonal antibodies has emerged as an effective disease-modifying treatment for metastatic RCC. There is emerging data across other solid tumors of the potential efficacy of neoadjuvant PD-1 blockade, and preclinical evidence supporting a neoadjuvant over adjuvant approach. PROSPER RCC is a Phase III, randomized trial evaluating whether perioperative nivolumab increases recurrence-free survival in patients with high-risk RCC undergoing nephrectomy. The neoadjuvant component, intended to prime the immune system for enhanced efficacy, distinguishes PROSPER from other purely adjuvant studies and permits highly clinically relevant translational studies.

Future oncology (London, England). 2019 Apr 10 [Epub ahead of print]

Hiten D Patel, Maneka Puligandla, Brian M Shuch, Bradley C Leibovich, Anil Kapoor, Viraj A Master, Charles G Drake, Daniel Yc Heng, Primo N Lara, Toni K Choueiri, Deborah Maskens, Eric A Singer, Scott E Eggener, Robert S Svatek, Walter M Stadler, Suzanne Cole, Sabina Signoretti, Rajan T Gupta, Marc Dror Michaelson, David F McDermott, David Cella, Lynne I Wagner, Naomi B Haas, Michael A Carducci, Lauren C Harshman, Mohamad E Allaf

Department of Urology, The James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Department of Biostatistics & Computational Biology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA., Department of Urology, Yale School of Medicine, New Haven, CT, USA., Department of Urology, Mayo Clinic, Rochester, MN, USA., Division of Urology, McMaster University, Hamilton, ON, Canada., Department of Urology, Emory University School of Medicine, Atlanta, GA, USA., Division of Hematology/Oncology, Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY, USA., Tom Baker Cancer Center, Calgary, AB, Canada., Department of Internal Medicine, University of California Davis School of Medicine, Sacramento, CA, USA., Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA., Kidney Cancer Canada, Toronto, Ontario, Canada., Section of Urologic Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA., Section of Urology, University of Chicago, Chicago, IL, USA., Department of Urology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA., Department of Medicine (Hematology/Oncology), University of Chicago, Chicago, IL, USA., Department of Medicine (Hematology/Oncology), University of Texas Southwestern Medical Center, Dallas, TX, USA., Department of Pathology, Brigham & Women's Hospital, Boston, MA, USA., Departments of Radiology & Surgery & The Duke Cancer Institute, Duke University Medical Center, Durham, NC, USA., Massachusetts General Hospital Cancer Center, Boston, MA, USA., Division of Hematology-Oncology & Cancer Biology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA., Department of Medical Social Sciences, Northwestern University Feinberg School of Medicine, Chicago, IL, USA., Department of Social Sciences & Health Policy, Wake Forest School of Medicine, Winston-Salem, NC, USA., Division of Hematology/Oncology, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA.

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