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. While many patients with early stage kidney cancer can be cured by removal of the tumor and kidney (nephrectomy'), upward of 40% of patients can recur due to microscopic spread of the cancer prior to surgery. Adding anticancer drugs that are effective in the metastatic setting to surgery has potential to eliminate the microscopic disease and increase cure rates. The PROSPER renal cell carcinoma study is testing whether adding nivolumab, a drug that engages the immune system to better recognize, fight and eliminate the cancer, will improve disease control over surgery alone. Nivolumab will be given before and after surgery to see if it reduces the chance of the disease returning and decreases death from kidney cancer compared with patients receiving surgery only.