Introduction:

Utility of cytoreductive nephrectomy (CN) in metastatic renal cell carcinoma (mRCC) has been questioned utilizing data from patients treated with tyrosine kinase inhibitor (TKI) therapy as first line. We sought to compare outcomes of CN in patients who underwent TKI versus those who underwent Immuno-Oncology (IO) therapy.

Methods:

Multicenter retrospective analysis of patients from the REMARCC (REgistry of MetAstatic RCC) database. The cohort was divided into patients receiving TKI vs. IO as first-line therapy [TKI-CN vs. IO-CN]. Primary outcome was all-cause mortality (ACM)/overall survival (OS). Secondary outcome was cancer-specific mortality (CSM)/cancer-specific survival (CSS). Cox proportional hazards multivariable analysis (MVA) was used to elucidate predictive factors for ACM, CSM, and RFS. Kaplan Meier Analysis (KMA) was performed to analyze 5-year OS and CSS between TKI-CN vs. IO-CN.

Results:

189 patients (148 TKI-CN vs 41 IO-CN; median follow-up 23.2 months). No inter-group differences were noted for primary tumor size (9.0 vs 9.3 cm, p=0.603) or median number of metastases (p=0.354). MVA demonstrated increasing number of metastases (HR=1.06, p=0.015), increasing primary tumor size (HR=1.10, p=0.043), TKI receipt (HR=2.36, p=0.015), and post CN initiation of systemic therapy (HR=1.49, p=0.039) to be associated with worsened ACM. Increasing number of metastases at diagnosis (HR=1.07, p=0.011), increasing primary tumor size (HR=1.12, p=0.018), TKI receipt (vs IO, HR=5.43, p=0.004), and post-CN initiation of systemic therapy (HR=2.04, p<0.001) were independently associated with worsened CSM. Comparing IO-CN vs. TKI-CN groups, KMA demonstrated greater 5-year OS (51% vs 27%, p<0.001) and 5-year CSS (83% vs 30%, p<0.001) for IO, which persisted in analysis of intermediate to poor risk patients: 5-year OS (50% vs 30%, p<0.001).

Conclusion:

In patients who received cytoreductive nephrectomy, receipt of IO therapy was associated with improved survival outcomes compared to TKI therapy. Furthermore, initiation of pre-CN systemic therapy was associated with improved outcomes. Our findings call into question the applicability of clinical trial data from cytoreductive nephrectomy in the TKI era to cytoreductive nephrectomy in the IO era.

Funding: Stephen Weissman Kidney Cancer Fund