Long-term oncologic outcomes of metastatic clear-cell renal cell carcinoma after local therapy alone

Purpose Oligometastatic clear-cell renal cell carcinoma (ccRCC) represents a heterogeneous entity that can, in select cases, be managed with primary tumor resection and complete local treatment at all metastatic sites, rendering a patient metastatic with no evidence of disease (M1 NED). M1 NED patients have improved overall survival, although previous cohorts are relatively small and heterogeneous. We sought to identify the natural history of M1 NED ccRCC to clinical trial findings and to optimize management strategies. Materials and methods Patients with synchronous metastatic ccRCC treated with local therapy alone and considered radiographically M1 NED at our institution between 1989 and 2023 were retrospectively evaluated. Survival probabilities used a combination of Kaplan-Meier estimator, log-rank test, and multivariable Cox proportional hazards regression. When available, limited genomic data obtained using the MSK-IMPACT targeted panel was correlated with outcomes. Results 85 patients met inclusion criteria. One-year disease free survival (DFS) was 53% (95% CI: 42 to 63%). Sarcomatoid features predicted shorter DFS (HR 2.62, CI: 1.08, 6.34, P = 0.03). Time from first disease recurrence to second recurrence was longer among patients with initial DFS ≥2 years (median 42 vs. 15 months, log-rank P = 0.005). A total of 18 patients (21%) underwent targeted genomic sequencing; higher fraction of genome altered and CDKN2A copy number loss were associated with shorter DFS. Findings were limited by cohort size. Conclusions Most M1 NED ccRCC patients will experience disease recurrence, although certain baseline risk factors appear to predict earlier recurrence. Prognostic biomarkers are needed to predict outcomes and facilitate patient management.