Local definitive therapy (LDT) utilization patterns and outcomes in chromophobe renal cell carcinoma (chRCC) with metachronous metastasis: A multi-institution study.
Authors: Nazli Dizman, Sahil D Doshi, Andrea Knezevic, Ardit Feinaj, Nicolas Sayegh, Charbel Hobeika, Reza Alaghehbandan, Hal Rives, Zeynep Busra Zengin, David A. Braun, Matthew R. Zibelman, Bradley Alexander McGregor, Hans J. Hammers, Yasser Ged, Moshe C. Ornstein, Pavlos Msaouel, Andrew Warren Hahn, Martin H Voss
Journal: Journal of Clinical Oncology (2025)

503 Background: LDTs, including surgical resection, radiation treatment and ablation/embolization, can be employed to achieve a disease-free state in indolent oligometastatic RCC irrespective of subtype. However, the efficacy of LDTs in chRCC, a rare subtype, has not been investigated. We utilized a multi-institutional chRCC dataset to examine LDT use patterns and associated duration of disease control. Methods: Clinical and treatment characteristics of patients with chRCC and metachronous metastases were retrospectively collected from four institutions. Patients with LDT as the first metastasis-directed intervention comprised the LDT cohort, while those who started systemic treatment (ST) upfront were included in the ST cohort. Wilcoxon rank-sum test and Fisher’s exact test were used for comparison of continuous and categorical variables, respectively. Systemic treatment-free survival (STFS, duration between upfront LDT and subsequent ST initiation or last follow-up) was calculated by Kaplan-Meier method. Results: 104 patients were included: 48 in the LDT cohort and 56 in the ST cohort.Median age and gender were comparable across the two cohorts. Compared to patients who initiated ST, patients who underwent LDT had a longer interval between nephrectomy and metastatic disease diagnosis (49 months [IQR 30. 93] vs 14 months [IQR 4, 47], p &lt;0.001), were less likely to have tumors with sarcomatoid dedifferentiation (6% vs 34%, p &lt;0.001), had an earlier disease stage at initial diagnosis (Stage I 33% vs 9%, Stage II 12% vs 31%, Stage III 55% vs 56%, p=0.004) and were more likely to have a single metastatic site (79% vs 52%, p=0.002). In the LDT cohort, 39 (81%) patients underwent surgery, 7 (14%) radiation and 4 (8%) ablation/embolization. The majority (30 [61%]) underwent a single LDT, while serial LDTs were utilized in the remainder: 12 (25%) with 2 LDTs and 6 (12%) with ≥3. The most frequently treated sites with LDT were the lymph node (27%), soft tissue (23%) and liver (15%). The median interval between first and second LDT was 20 months (IQR 7, 32), and between the second and third LDT was 7 months (IQR 1, 10). At a median follow-up of 60 months, median STFS was 32 months (95% CI, 20, 46). One- and two-year STFS rates were 84% and 62%. Conclusions: This is thefirst study to systematically evaluate LDT use and outcomes in chRCC managed at centers of expertise. LDTs were more frequently utilized in patients with single-organ metastasis, longer time between nephrectomy and recurrence, and absence of sarcomatoid dedifferentiation. In a carefully selected population, LDTs can lead to clinically meaningful treatment-free interval in chRCC.