Outcomes of Cytoreductive Nephrectomy in Patients Undergoing TKI Versus IO Therapy

An analysis of the REgistry of MetAstatic RCC (REMARCC) database presented at the 24th Annual Meeting of the Society of Urologic Oncology compared the survival outcomes of patients with metastatic renal cell carcinoma (mRCC) who underwent cytoreductive nephrectomy as well as first-line tyrosine kinase inhibitor (TKI) or immuno-oncology (IO) therapy.

Margaret Frances Meagher, MD, and colleagues conducted a multicenter retrospective analysis of patients from the REMARCC database. A total of 189 patients with mRCC were sampled, among whom 148 received TKI as first-line therapy and 41 received IO first-line therapy.

The primary outcome of the analysis was all-cause mortality/overall survival (OS). The secondary outcome was cancer-specific mortality/cancer-specific survival (CSS).

Researchers utilized Cox proportional hazards multivariable analysis to identify predictive factors for all-cause mortality, cancer-specific mortality, and recurrence-free survival. Kaplan-Meier analysis was performed to analyze 5-year OS and CSS between the patient cohorts.

The median follow-up was 23.2 months, and no intergroup differences were noted for primary tumor size (9.0 cm vs 9.3 cm for TKI and IO, respectively; P=.603) or median number of metastases (P=.354).

The multivariable analysis showed an increasing number of metastases (hazard ratio [HR], 1.06; P=.015), increasing primary tumor size (HR, 1.10; P=.043), TKI receipt (HR, 2.36; P=.015), and post-cytoreductive nephrectomy initiation of systemic therapy (HR, 1.49; P=.039) to be associated with worse all-cause mortality.

Similarly, an increasing number of metastases at diagnosis (HR, 1.07; P=.011), increasing primary tumor size (HR, 1.12; P=.018), TKI receipt (HR, 5.43; P=.004), and post-cytoreductive nephrectomy initiation of systemic therapy (HR, 2.04; P<.001) were independently associated with worsened cancer-specific mortality.

When comparing the IO versus TKI groups, researchers found a greater 5-year OS (51% vs 27%, respectively; P<.001) and 5-year CSS (83% vs 30%, respectively; P<.001). This trend was also observed in intermediate-to-poor-risk patients (5-year OS, 50% vs 30%, respectively; P<.001).

“In patients who received cytoreductive nephrectomy, receipt of IO therapy was associated with improved survival outcomes compared [with] TKI therapy,” Dr. Meagher and colleagues concluded, adding that initiation of pre-cytoreductive nephrectomy 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.”