Multimodal management of oligometastatic and oligoprogressive renal cancer patients with extra-lung metastases: The KAIROS study.
Authors: Alessandra Dimino, Mimma Rizzo, Ivan Fazio, Carmelo Carlo Arcara, Gianluca Mortellaro, Lorenzo Antonuzzo, Vincenza Conteduca, Helga Maria Alessandra Lipari, Antonella Mazzonello, Mikol Modesti, Giuseppe Badalamenti, Grazia Sirgiovanni, Sara Inguglia, Laura Algeri, Tancredi Didier Bazan Russo, Sergio Bracarda, Camillo Porta, Antonio Russo, Lorena Incorvaia
Journal: Journal of Clinical Oncology (2025)

507 Background: Patients with oligometastatic (OM-) or oligoprogressive renal cell carcinoma (OP-RCC) may benefit from metastasis-directed therapy (MDT) alone or in combination with systemic therapies. Literature data are available for IMDC favorable-risk patients with low-volume and asynchronous metastases, particularly to the lung. However, OM- and OP-RCC represent a heterogeneous population, and the current knowledge on the use of MDTs on extra-lung metastases remains limited. Methods: This was a real-world, multicenter, observational, retrospective study to assess the Time-to-Subsequent-Systemic-Treatment (TSST) in OM- and OP-RCC patient populations with at least 1 extra-lung metastasis undergoing MDTs [stereotactic body radiation therapy (SBRT), or surgical metastasectomy (SM)], during active surveillance (Cohort 1-OM), or upfront systemic treatments (ST) (Cohort 2-OP), as part of routine clinical care. Results: A total of 138 patients were included: 81 (58.7%) in the OM, and 57 (41.3%) in the OP cohort. Bone (44 lesions, 22.4 %), lymph nodes (33 lesions, 16.8 %), brain (28 lesions, 14.3 %), adrenal gland (26 lesions, 12.3%), soft tissues (14 lesions, 7.1%), liver (11 lesions, 5.6%), contralateral kidney (12 lesions, 6.1%), pancreas (10 lesions, 5.1%), peritoneum (7 lesions, 3.7%) or others (11 lesions, 5.6%) were the sites treated with MDT, for a total of 196 lesions: 139 metastases treated with SBRT (70.9%), and 57 (29.1%) treated with SM. In the Cohort 1-OM, a total of 112 lesions were treated with MDTs: 66 with SBRT (58.9%) and 46 with SM (41.1%). The median TSST was 43.0 months (95%CI 24.09-61.90); 73.2% and 60.5% of patients were free from systemic therapy at 1 and 2 years, respectively. In the Cohort 2-OP, 84 oligoprogressive lesions were treated: 73 with SBRT (86.9%) and 11 with SM (13.1%). Concomitant ST were: Tyrosine Kinase Inhibitors (TKIs) alone (25 pts, 43.9%), immune-oncology (IO) combination [IO-TKI (16 pts, 28.1%) or IO-IO (2 pts, 3.5%)], nivolumab (12 pts, 21.0%) or everolimus ± TKI (2 pts, 3.5%). The median TSST was 31.0 months (95%CI 24.32-37.68); freedom from subsequent systemic therapy at 1 and 2 years was 66.7% and 45.6%, respectively. Safety profile was favorable, with 1 Grade 3 and any Grade 4 SBRT-related toxicities or surgical complications reported. Conclusions: OM and OP-RCC do not have a clear standard of care, and data supporting the multimodal management of extra-lung metastases are lacking. Our real-world data suggest that the use of the SBRT and SM for the treatment of extra-lung metastases in patients undergoing AS or ST can be a useful strategy within a multidisciplinary approach, allowing the delay of systemic treatment initiation or escalation, with favorable toxicity rates.