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

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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.