Efficacy of immune checkpoint inhibitor combination therapy prior to nephrectomy in advanced renal cell carcinoma: A retrospective pilot study

Abstract

Renal cell carcinoma (RCC) affects 10%-20% of patients annually, often with metastases present. This study evaluated the impact of systemic therapy before nephrectomy in patients with unresectable or metastatic renal cell carcinoma (RCC). Patients receiving upfront immune checkpoint inhibitor (ICI) combination therapy showed significantly improved progression-free survival (PFS) compared to nephrectomy alone (2-year PFS: 62.3% vs. 17.4%; p = 0.036), while upfront tyrosine kinase inhibitor (TKI) therapy did not (2-year PFS: 18.2% vs. 12.3%; p = 0.545). Surgery-related outcomes did not differ significantly between groups. ICI therapy maintained tumour reduction rates better than TKI therapy. The study highlights the potential benefits of ICI combination therapy over TKI therapy in advanced RCC, suggesting further research is needed to confirm these findings.

Keywords: cytoreductive surgery; immune checkpoint inhibitor; metastatic tumour; progression‐free survival; renal cell carcinoma; unresectable tumours.

FIGURE 1

(A) Comparison of patient characteristics between the upfront nephrectomy (uN) group versus upfront VEGF‐targeted therapy (TKI) group or upfront immune checkpoint inhibitor combination therapy (uICI) group. A table on the left indicates variables before propensity score matching (PSM), and a table on the right indicates variables after PSM. Chi‐square or Mann–Whitney U test for statistical analysis. BMI, body mass index; IMDC, International Metastatic RCC Database Consortium; IQR, interquartile range. (B) Kaplan–Meier curves depict progression‐free survival, comparing the uN group versus the uTKI group and the uN group versus the uICI group. Panels on the left show data before propensity score matching (PSM), and those on the right show data after PSM. Log‐rank test was used for analysis. (C,D) Comparison of surgical‐related factors, including blood loss volume (mean value ± standard error) during nephrectomy and postoperative complication grade based on the Clavien–Dindo classification, and surgical pathology obtained by nephrectomy was performed between the groups after PSM. Chi‐square or Mann–Whitney U test for statistical analysis. (E) Swimmer plot of clinical course of all patients treated with either VEGF‐targeted therapy or immune checkpoint inhibitor combination therapy (n = 23; before PSM). (F) Best response and final response before nephrectomy for target lesions based on the maximal percentage of tumour reduction. PD, progression disease.