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

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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 <0.001), were less likely to have tumors with sarcomatoid dedifferentiation (6% vs 34%, p <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.