Transforming the Perioperative Treatment Paradigm in Non-Metastatic RCC-A Possible Path Forward

Area of Science:

• Oncology
• Immunotherapy
• Renal Cell Carcinoma Research

Background:

• No adjuvant systemic therapy currently improves overall survival for non-metastatic renal cell carcinoma (RCC).
• Nivolumab, an anti-PD-1 antibody, has shown efficacy in metastatic RCC and is well-tolerated.
• Preclinical models suggest neoadjuvant PD-1 blockade may be more beneficial than adjuvant therapy.

Purpose of the Study:

• To evaluate the efficacy of perioperative nivolumab in improving clinical outcomes for patients with high-risk localized and locally advanced RCC.
• To increase cure rates and recurrence-free survival (RFS) in non-metastatic RCC through a multidisciplinary approach.

Main Methods:

• The PROSPER RCC trial is a global, randomized, phase 3 study enrolling 766 patients with clinical stage ≥T2 or node-positive M0 RCC.
• The investigational arm receives neoadjuvant nivolumab before surgery followed by adjuvant nivolumab for 9 months.
• The control arm receives standard surgical resection followed by observation.

Main Results:

• The trial is powered to detect a 14.4% absolute benefit in RFS at 5 years (from 55.8% to 70.2%).
• The study is also powered to demonstrate a significant overall survival benefit.
• Key safety, feasibility, and quality of life endpoints are being assessed.

Conclusions:

• Perioperative nivolumab is being investigated as a novel strategy to improve outcomes in non-metastatic RCC.
• The PROSPER RCC trial aims to establish a new standard of care for high-risk localized and locally advanced RCC.
• Correlative studies will explore the impact of the immune microenvironment on treatment response.