3407 - Circulating Tumor DNA Dynamics in Oligometastatic Urothelial Carcinoma Treated with Stereotactic Body Radiation Therapy
Presenter(s)
D. Zhao1,2, C. Chiodo1,2, V. Yin3, R. Li4, S. M. Gilbert4, P. Spiess4, L. W. Zemp4, W. J. Sexton4, M. Poch4, J. Chatzkel4, J. S. Chadha4, J. A. Kish4, C. SAM5, A. Patel4, M. Liu4, K. Rayn1, J. F. Torres-Roca1, P. A. S. Johnstone1, K. Yamoah1, and G. D. D. Grass1; 1Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, 2University of South Florida Morsani College of Medicine, Tampa, FL, 3Department of Biostatistics and Bioinformatics, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, 4Department of Genitourinary Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, 5Department of Hematology/Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL
Purpose/Objective(s):
Stereotactic body radiotherapy (SBRT) is an effective metastasis-directed therapy (MDT), though data in urothelial carcinoma (UC) remains limited. There is little guidance on selection for optimal SBRT candidates in oligometastatic (OM) UC. Plasma circulating tumor DNA (ctDNA) provides data on the presence of metastatic disease and may complement image-based response assessment after SBRT. This study assesses ctDNA dynamics and outcomes in patients with UC treated with SBRT in the OM state.Materials/Methods:
We performed a retrospective analysis on consecutive patients treated with SBRT for image-defined or biopsy-proven oligorecurrent (OR), de novo oligometastatic (dn-OM), or oligoprogressive (OP) UC between January 2022 to December 2025 who also underwent plasma ctDNA assessment with a tumor-informed commercial assay before and/or after SBRT. Medical charts were queried for clinicopathologic features, treatment and outcomes. Descriptive statistics summarized cohort features. Patients were stratified as ctDNA (+) or ctDNA (-) after SBRT and the Kaplan-Meier method estimated progression-free survival (PFS) with log-rank test for comparisonsResults:
Twelve patients who underwent SBRT to a total of 17 lesions (10 OR, 2 dn-OM and 5 OP) were identified. Four patients (33.3%) had systemic therapy pre- and post-SBRT. Ten patients (83.3%) were staged with FDG-PET and a total of 7 (58.3%) had biopsy-proven oligometastases. Most common treated sites were lymph node (58.8%) and lung (23.5%) with a median SBRT dose and fractionation of 40 Gy (range: 35-55) and 5 fractions (range: 5-10), respectively. A total of 107 ctDNA measurements (45 pre-SBRT; 62 post-SBRT) were obtained with a median of 8 (range: 2-25) per patient. Nine (75%) patients had pre- and post-SBRT ctDNA [8 ctDNA (+) and 1 ctDNA (-)], while 3 had post-SBRT ctDNA only. SBRT resulted in ctDNA clearance in 6 of 8 (75%) pre-SBRT ctDNA (+) patients and the single pre-SBRT ctDNA (-) patient remained so. Of the 3 patients with only post-SBRT ctDNA, 2 (66.7%) were ctDNA (-) and 1 (33.3%) was ctDNA (+). After SBRT, 9 of 12 (75%) patients were ctDNA (-). At a median post-SBRT follow-up time of 413 days (range: 64-1347), local control was 100%. The 3 ctDNA (+) patients developed radiographic and biopsy-proven disease at new sites and all 9 ctDNA (-) patients remain disease free. The 1-year PFS in post-SBRT ctDNA (+) and ctDNA (-) groups was 33% and 100%, respectively, and post-SBRT ctDNA (-) status was associated with better PFS (p<0.0008). Regarding systemic therapy, six (50%) patients have avoided, 2 (16.7%) have delayed (412 and 250 days), and 4 (33.3%) continued their current regimen.Conclusion:
SBRT is an effective MDT for oligometastatic UC. ctDNA may facilitate optimized selection criteria for SBRT and complement surveillance imaging. Our hypothesis-generating results provide a basis for additional studies integrating ctDNA dynamics in MDT with SBRT and may provide insights on patient selection to avoid and/or delay systemic therapy.