# Deferred Versus Upfront Cytoreductive Nephrectomy in MetaStatic Renal Cell Carcinoma: Comparative Survival Analysis in the Immunotherapy Era

## TL;DR

This study compares the timing of a kidney surgery in advanced kidney cancer patients and finds that delaying the surgery may improve survival in some patients receiving immunotherapy.

## Contribution

The study provides new evidence that deferred cytoreductive nephrectomy may offer better survival outcomes in selected metastatic renal cell carcinoma patients in the immunotherapy era.

## Key findings

- Deferred CN was associated with superior overall and disease-specific survival compared to upfront CN in selected patients.
- The survival advantage of deferred CN diminished after two years of follow-up.
- Deferred CN showed comparable other-cause specific survival to upfront CN.

## Abstract

The treatment landscape for metastatic renal cell carcinoma (mRCC) has undergone significant transformation, and cytoreductive nephrectomy (CN) persists as a viable intervention option in the immunotherapy era. However, the optimal timing of CN has not yet been clearly determined. In this large-scale, population-based, real-world study, we identified 1892 mRCC patients who underwent deferred CN (dCN) or upfront CN (uCN) from the SEER database. To capture contemporary nationwide treatment patterns, we included only patients diagnosed after 2016. Using propensity score matching, sensitivity, sub-group, and landmark analyses, we found that dCN was associated with superior survival compared to uCN in selected mRCC patients receiving immunotherapy, highlighting the importance of careful patient selection.

Background: The optimal timing of cytoreductive nephrectomy (CN) in metastatic renal cell carcinoma (mRCC) remains a subject of debate, particularly in the immunotherapy era. This study compares survival outcomes between deferred CN (dCN) and upfront CN (uCN) in mRCC patients receiving modern immunotherapy regimens in the real-world setting. Methods: We retrospectively analyzed the SEER database for mRCC patients diagnosed between 2016 and 2021 who underwent dCN or uCN. The primary endpoint was overall survival (OS), while the secondary endpoints were disease-specific survival (DSS) and other-cause specific survival (OCSS). Statistical analyses included propensity score matching (PSM), Kaplan–Meier survival curves, Cox proportional hazards modeling, as well as sensitivity, subgroup, and landmark analyses. Results: A total of 1892 mRCC patients were included, with 346 patients (18.3%) undergoing dCN and 1546 patients (81.7%) receiving uCN. Patients in the uCN group were characterized with lower T stage (p < 0.001), while those in the dCN group exhibited a higher incidence of lymph node involvement (p = 0.02) and sarcomatoid dedifferentiation (p = 0.002). Following 1:2 PSM, dCN demonstrated significantly better OS and DSS, but comparable OCSS to uCN. The sensitivity and subgroup analyses suggested that dCN may substantially improve the prognosis of mRCC patients across conditions. The landmark analysis showed that the survival advantage of dCN diminished after two years of follow-up. Conclusions: dCN may be associated with improved survival outcomes compared to uCN in selected mRCC patients receiving immunotherapy, and careful patient selection for dCN or uCN is essential.