Perioperative Immune-Checkpoint Inhibition in Renal Cell Carcinoma: Lessons Learned and Future Directions

Background/Objectives: Localized renal cell carcinoma (RCC) unfortunately has a suboptimal rate of metastatic recurrence. Immune-checkpoint inhibition (ICI), commonly known as immunotherapy, is being increasingly utilized in the management of other localized cancers. The objective of this paper is to review the most recent literature as it pertains to ICI in localized RCC, highlight major lessons learned across clinical trials, and then suggest new directions based on these lessons and on new technologies. Methods: English-language articles were identified in PubMed/Google Scholar/Scopus. Selection priority was placed on prospective clinical trials. Particular emphasis was placed on disease-free survival (DFS), overall survival (OS), and clinical trial design. Novel approaches to the diagnosis, risk stratification, and management of RCC were also queried. Results: The KEYNOTE-564 trial demonstrated DFS and OS benefits of adjuvant pembrolizumab in high-risk clear cell RCC. Although discordance exists with adjuvant ICI in the IMmotion-010 and CheckMate-914 trials, preliminary data from the RAMPART trial also reveal a DFS benefit for adjuvant durvalumab-tremelimumab. The PROSPER trial failed to show a benefit for perioperative nivolumab, but ongoing neoadjuvant/perioperative ICI trials show promise. Subtle differences in design exist across the mentioned trials and are arguably clinically significant. Several new diagnostic tools and technologies have been identified for use in RCC. Conclusions: By applying the lessons learned from the differences in clinal trial design, along with leveraging new diagnostic tools and technologies, there is great potential to more accurately stratify risk amongst patients with localized RCC and therefore better identify the patients who are most likely to benefit from perioperative ICI.