Initial and Repeat Metastasis-Directed Therapy in Systemic Therapy-Naïve Oligometastatic Renal Cell Carcinoma: Oncologic Outcomes and Risk-Based Stratification.

Abstract

Metastasis-directed therapy (MDT) offers the potential to delay systemic treatment in oligometastatic renal cell carcinoma (OM-RCC); however, outcomes in clinical practice, particularly with repeat MDT in patients naïve to systemic therapy, are not well characterized. We analyzed 133 patients with OM-RCC who were naïve to systemic therapy (with up to five lesions) and treated with MDT: metastasectomy, stereotactic body radiotherapy, or radiofrequency ablation. In total, 38 patients underwent a second MDT for subsequent relapse without systemic therapy. Kaplan-Meier and Cox regression analyses evaluated progression-free survival (PFS), systemic therapy-free survival (STFS), and overall survival (OS). A time-varying Cox model accounted for intrapatient correlation when comparing PFS between MDT sessions. A two-factor risk score was constructed using disease-free interval (DFI < 1 year) and metastatic burden (two or more lesions). With a median follow-up of 49.8 months, 5-year STFS and OS were 44.9 and 85.0%, respectively. Two-year PFS was similar between the first (47.9%) and second MDT (39.9%, P = 0.996). After the first MDT, DFI < 1 year and two or more lesions independently predicted inferior PFS, STFS, and OS. After the second MDT, only DFI < 1 year remained significant for PFS. The composite risk score, assigning one point each for DFI < 1 year and two or more lesions, effectively stratified outcomes, with 2 year PFS rates of 63.6% (score 0), 33.5% (score 1), and 9.1% (score 2) after the first MDT. MDT provides durable disease control and defers systemic therapy in systemic therapy-naïve OM-RCC. Repeat MDT offers comparable outcomes to initial treatment in selected patients. A simple risk score integrating DFI and metastatic burden may guide patient selection and shared decision-making. In systemic therapy-naïve oligometastatic RCC, metastasis-directed therapy (MDT) provides durable systemic therapy-free and overall survival. Repeat MDT, when applied to carefully selected patients, achieves progression control comparable to that of the initial treatment. A simple two-factor risk score incorporating a disease-free interval of < 1 year and ≥ 2 effectively stratifies patients into favorable and poor prognostic groups. This tool offers clinicians a practical means of triaging candidates, optimizing the timing of MDT, and determining when early systemic therapy should be considered.