Objective: To evaluate and compare the outcomes of metastatic renal cell carcinoma (mRCC) patients, with or without sarcomatoid features, who underwent cytoreductive nephrectomy (CN) before or after systemic therapies (ST).

Methods: Synchronous metastatic RCC patients of IMDC intermediate- and high-risk diagnosed between January 2011 to December 2022, treated with CN before or after ST, and with histological documentation of the presence or absence of sarcomatoid features in nephrectomy specimens were identified using the Canadian Kidney Cancer information system (CKCis). Patients were classified by treatment sequence received: (1) CN after ST (2) CN before ST.  Inverse probability of treatment weighting using propensity scores was used to balance for covariates. Cox proportional hazards models were used to assess the impact of initial treatment received on overall survival (OS).

Results: Of 709 eligible patients, 105 were treated with CN after ST and 604 with CN before ST. 75% were male, and the majority (70%) received targeted therapies (TT) used alone. In non-sarcomatoid patients (80 CN after ST and 454 CN before ST), treatment with CN after ST (CR: 12.5%) was not associated with improved OS compared CN before ST (CR: 2.2%) (median of 60 versus 48 months, HR 0.84, 95% CI 0.64-1.11). In sarcomatoid patients (25 CN after ST and 150 CN before ST), a non-statistically significant result shows that CN before ST (CR: 5.3%) was also not associated with better survival (median of 24 versus 36 months, HR 1.10, 95% CI 0.70-1.73).

Conclusion: In conclusion, this study demonstrated that, no matter the sarcomatoid status, there is no statistical difference between receiving CN after ST or CN before ST. The timing of CN could potentially be linked more so to clinical assessments than the knowledge of sarcomatoid status.