Mohamad E. Allaf, MD

Mohamad E. Allaf, MD, reviews current literature on the role of neoadjuvant and adjuvant immunotherapy in treating localized renal cell carcinoma (RCC). He begins by establishing that surgical monotherapy fails to cure a significant proportion of patients with “localized” RCC thanks to micrometastatic disease.

Dr. Allaf then discusses how the inclusion of neoadjuvant therapies reduces the size of the tumor, controls potential metastases at the earliest point, and provides a litmus test for how appropriate it would be to treat the patient with surgical monotherapy. He also addresses adjuvant therapies, which can lower the likelihood of recurrence, and prolong patient survival. He acknowledges that older studies of adjuvant Tyrosine Kinase Inhibitor (TKI) therapy for RCC were negative, resulting in high toxicity and low effectiveness in treatment.

Dr. Allaf compares the performance of recent neoadjuvant checkpoint inhibitors in the metastatic setting to the current standard of care, demonstrating that the durability of disease response continued even after the discontinuation of the therapy. He then explores the rationale and early results supporting the administration of neoadjuvant therapy in localized RCC, and how they laid the groundwork for the PROSPER trial.

The PROSPER trial was a Phase III international, randomized trial which examined the effect of a single dose of neoadjuvant checkpoint inhibitors 7-28 days before partial or radical nephrectomy. He presents the study design, the cohort composition, and the results, which did not support the use of neoadjuvant therapy for RCC patients.

Dr. Allaf concludes by presenting multiple recent studies supporting the use of adjuvant therapy for intermediate-high-risk and high-risk RCC patients. While adjuvant therapy has been approved for use by the FDA, additional trials and investigations are still needed to advance the field.