Efficacy of immunotherapy-based immediate cytoreductive nephrectomy vs. deferred cytoreductive nephrectomy in metastatic renal cell carcinoma

- OBJECTIVE: This study was performed to evaluate the efficacy of immediate cy- toreductive nephrectomy (CRN) followed by pro- grammed cell death factor-1 (PD-1) inhibitors vs. deferred CRN after the administration of 4 cycles of neoadjuvant therapy using nivolumab preced- ing the debulking and postoperative chemothera- py in metastatic renal cell carcinoma (mRCC). PATIENTS AND METHODS: We recruited 84 patients with primary mRCC admitted to our On- cology Department from 2018 to 2020 and ran- domized them 1:1 to receive either CRN followed by nivolumab (control group) or 4 cycles of neo- adjuvant therapy using nivolumab before CRN and postoperative chemotherapy (study group), with 42 patients in each group. The primary clini- cal endpoints were the clinical efficacy and safe- ty of the PD-1 antibody. Clinical outcomes were assessed 3 months after treatment. RESULTS: Patients were followed-up for 10-52 months, with a median follow-up period of 40.50 months. The control group reported 2 cases of complete remission and 10 cases of partial re- mission, with an objective response rate (ORR) of 28.57% (12/42). The study group reported 4 cases of complete remission and 14 cases of partial re- mission with an ORR of 42.86% (18/42). No signif- icant differences in the ORR were identified be- tween the two groups (p > 0.05). Progression-free survival of the patients was significantly extend- ed from 30 months (19-51) to 43 months (38-76) af- ter administrating the PD-1 inhibitors before the debulking (HR = 0.501, 95% CI: 0.266 to 0.942). There were no significant differences in the medi- an survival of patients between the two groups [44 months (38-79) vs. 44 months (32-81)] (HR = 0.814, 95% CI: 0.412 to 1.612). The two protocols had a similar safety profile. CONCLUSIONS: Nivolumab administration preceding delayed CRN provides significant progression-free survival benefits for patients with mRCC, but its impact on overall survival re- quires further investigations.