S966
Clinical - Oligometastatic cancer
ESTRO 2026
1-5 metastases to continuing standard of care (SOC) systemic therapy ± MDT.1-3 Six tumor-specific baskets (pancreas, breast, kidney, two prostate, and “Other”) were independently randomized and powered for progression-free survival (PFS). Plasma was collected at enrollment (ongoing SOC without radiologic progression), 3-month follow-up, and progression and profiled with the tumor-agnostic, methylation-based Guardant Reveal assay. Cox regressions were adjusted for arm, basket (tumor type), and stratification factors (number of metastases and prior systemic therapies). Results: Of 554 samples from 237 patients tested, 550 (99.3%) passed quality control. At enrollment, 115/237 patients (49%) had ctDNA detected, most commonly in pancreatic cancer (70%) and least commonly in prostate cancer (35%). Alterations were most often observed in TP53 (n=66), NF1 (n=18), and ATM (n=18). At enrollment, ctDNA(+) was associated with shorter PFS (HR 2.51, 95% CI 1.73-3.66, p<0.001), disease- specific survival (DSS) (HR 2.69, 95% CI 1.43-5.06, p=0.002), and overall survival (OS) (HR 2.05, 95% CI 1.20-3.67, p=0.009) (Figures 1-2). Prognostic signal was consistent across tumor types. Patients with both ctDNA(+) and ctDNA(-) had improved PFS with MDT+SOC vs SOC (p<0.05 for both subgroups; interaction p=0.6). Among 188 patients at 3-month follow-up, ctDNA was detected in 81 (43%) and associated with shorter PFS (HR 1.94, 95% CI 1.25-2.99, p=0.003), DSS (HR 3.66, 95% CI 2.04-6.57, p<0.001), and OS (HR 2.59, 95% CI 1.46-4.72, p=0.001). Differences in ctDNA clearance rates at follow-up between MDT+SOC (33%) and SOC (23%) were inconclusive (OR 1.65, 95% CI 0.65-4.20, p=0.3). Patients achieving ctDNA clearance had longer OS than those with persistent ctDNA(+) (HR 0.25, 95% CI: 0.08-0.64; p=0.003). Of 82 patients at progression, 65 (79%) were ctDNA(+), and ctDNA tumor fraction increased relative to 3-month follow-up (median 0.13 vs 0; p<0.001).Figure 1. Progression-free survival.
Figure 2. Overall survival.
Conclusion: In the largest exploration of ctDNA in a randomized trial of SOC ± MDT for oligometastatic disease, ctDNA detection was strongly and independently associated with multiple clinical outcomes. ctDNA clearance may represent a new immediate surrogate endpoint. As a
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