Introduction:

Treatment approaches for metastatic renal cell carcinoma (mRCC) have evolved over the recent years. In the cytokine era, cytoreductive nephrectomy (CRN) followed by systemic therapy was considered a standard treatment for mRCC. Evidence from the Cancer du Rein Metastatique Nephrectomie et Antiangiogéniques (CARMENA) and the Immediate Surgery or Surgery After Sunitinib Malate in Treating Patients with Metastatic Kidney Cancer (SURTIME) trials have questioned the role of CRN. However, with the evolution of targeted therapies and immunotherapies for mRCC, the role of CRN merits further consideration. The present study aims to provide real world data to better understand the role of CRN in mRCC.

Methods:

This retrospective cohort study used the TriNetX database of adult patients diagnosed with mRCC from 2005 till 2024 undergoing nephrectomy within a year of diagnosis. The primary outcome studied was 5-year survival rate. Trends and patterns of patients with mRCC undergoing CRN were analyzed over the past 20 years. Using relevant ICD-10 codes and CPT codes, cohorts of patients with mRCC receiving any kind of systemic therapy (n= 1776), Axitinib and Pembrolizumab (n= 470), Cabozantinib and Nivolumab (n=774), Lenvatinib and Pembrolizumab (n = 246), and Ipilimumab and Nivolumab (n= 958), were identified. Patients in these cohorts were classified into those who underwent CRN and those who did not, and after propensity matching (based on age, race, labs and multiple comorbidities), Kaplan-Meier survival analysis was done.

Results:

Since 2012, there has been a steady decline in the number of mRCC patients receiving CRN from an average of 10.79 CRNs per 100 cases of mRCC in 2012 to 4.93 in 2024 (Figure 1). The survival probability was significantly greater in patients who received systemic therapy followed by CRN when compared to these first-line systemic regimens alone (57.74% vs 45.02%, p<0.0001) with significant hazard ratio (1.56, 95% CI = 1.33-1.83) (Figure 2A). Similarly, for patients matched patients who received Axitinib and Pembrolizumab, survival probability was higher in those who received CRN (64% vs 53.3%, p=0.01, Hazard ratio 1.51, 1.08-2.09) (Figure 2B). This observation held true for patients receiving any of the first line recommended therapeutic combinations: Cabozantanib and Nivolumab (50.12% vs 40.38%, p = 0.0045, Hazard ratio: 1.37, 1.1-1.71) (Figure 2C), Lenvatinib and Pembrolizumab (37.4% vs 22.76%, p = 0.012, Hazard ratio: 2.5, 1.55-4.03) (Figure 2D), and Nivolumab and Ipilimumab (46.14% vs 56.43%, p = 0.005, Hazard ratio: 1.51, 1.22-1.87) (Figure 2E).

Conclusion:

Although the use of CRN in patients with mRCC has steadily declined since 2012, our large-scale real-world analysis demonstrates that CRN is associated with a significant survival benefit in most patients with mRCC receiving contemporary systemic combination therapy. These findings highlight the continued relevance of CRN in well selected patients and underscore the need to revisit CRN in the immunotherapy era with prospective studies.

Funding: N/A