Cytoreductive nephrectomy (CN) for metastatic renal cell carcinoma (mRCC) treated with immune checkpoint inhibitors (ICI) or targeted therapy (TT): A propensity score-based analysis.

Abstract

608 Background: The role of CN for mRCC treated with ICI is not well defined. Our aim was to evaluate the role of CN for mRCC treated by ICI or TT using a propensity score-based analysis. Methods: We retrospectively assessed patients who were diagnosed with de novo mRCC and who had started first line systemic therapy (ICI or TT) between 2009 and 2019 using the International Metastatic RCC Database Consortium (IMDC). Overall Survival (OS) was compared between patients receiving CN and those treated by systemic therapies alone, using the Kaplan-Meier method and Cox regressions, in the TT and ICI arms separately. In order to account for treatment selection bias, inverse probability of treatment weighting (IPTW) of propensity scores, based on 14 confounding variables, was used and variables were considered balanced if standardized mean difference (SMD) < 0.1. For variables with SMD≥0.1, residual confounding was adjusted for using multivariable models. Results: 3856 patients had been treated by TT (2470 CN+ & 1386 CN-) and 198 by ICI (143 CN+ & 55 CN-). Median follow-up was 38.5 months. After IPTW, baseline characteristics were largely balanced between the CN+ and CN- arms, in the TT and ICI groups (14/14 and 12/14 with SMD < 0.1, respectively). CN was associated with significantly improved OS in both the ICI (Hazard Ratio [HR] = 0.39 [0.19-0.83]) and TT (HR = 0.56 [0.51-0.62]) groups. The interaction term between CN and therapy type (ICI vs TT) was not statistically significant (p = 0.43). The point estimates of the HRs were consistent in sensitivity analyses using multivariable models. Conclusions: In a propensity score-based analysis, CN was found to be associated with a significant OS benefit in patients treated by either ICI or TT. While this study is not a substitute for randomized controlled trials (e.g. CARMENA), the results suggest that CN may still play a role in selected patients in the ICI era.[Table: see text]

Impact of Previous Nephrectomy on Clinical Outcome of Metastatic Renal Carcinoma Treated With Immune-Oncology: A Real-World Study on Behalf of Meet-URO Group (MeetUro-7b)

“…The authors, in a propensity score-based analysis, found that CN was associated with a significant OS benefit in patients treated with IO and TT both. 198 patients treated with IO were included in the analysis (32). In our multivariate analysis, nephrectomy retained a significant association with OS irrespective of the gland metastases and IMDC score.…”

“…The authors, in a propensity score-based analysis, found that CN was associated with a significant OS benefit in patients treated with IO and TT both. 198 patients treated with IO were included in the analysis ( 32 ).…”

First-Line Treatments for Metastatic Clear Cell Renal Cell Carcinoma: An Ever-Enlarging Landscape

“…Furthermore, in a propensity-score-based analysis from the IMDC group CN was associated with a significantly better OS in patients receiving targeted therapies (HR 0.56; 95% CI, 0.51 to 0.62) and ICIs (HR 0.39; 95% CI, 0.19 to 0.83). 68 Another important aspect of CARMENA is that this was a noninferiority trial and such trials have been shown to produce desirable results (ie, noninferiority for the experimental treatment) in greater than 80% of the studies. 69 , 70 Regardless, CN remains an important component in the therapeutic algorithm of patients with advanced kidney cancer.…”

Cytoreductive nephrectomy for synchronous metastatic renal cell carcinoma. Is there enough evidence?

“…Ten of them were from the Surveillance, Epidemiology, and End Results (SEER) database, 4 from International Metastatic RCC Database Consortium (IMDC), two from National Cancer Database (NCDB) and the rest were sin-gle or multi-center studies. Most common systemic agent used was sunitinib (Table 1), while there were three studies (2,40,42) comparing CN with the use of ICIs. These studies are of great importance, as they are the first retrospective studies on the role of CN in the immunotherapy era and demonstrated an OS benefit in patients treated with ICI plus CN compared to ICI alone (HR 0.23-0.39, Risk of bias assessment for randomized studies.…”

“…with 95% CI 0.15-0.37 and 0.19-0.83). Regarding the sequence of CN and ST, CN was administered before ST in 12 studies (21, 26-30, 32, 33, 35-37), before or after in 5 (23,38,(40)(41)(42), after in one study (25) while sequence was not specified in the rest.…”