Sequencing Ablation and Systemic Therapy in Colorectal Liver Oligometastases: An Upfront versus Delayed Approach Nationwide Analysis.

Abstract

Background The optimal sequencing of thermal ablation relative to systemic therapy for colorectal liver oligometastases (CLOM) remains controversial, with limited evidence to guide treatment planning. Purpose To compare the long-term survival outcomes of patients with CLOM receiving upfront ablation (UA) versus delayed ablation (DA) in combination with systemic therapies. Materials and Methods Patients with five or fewer CLOM (maximum lesion diameter, <5 cm) from 21 Chinese tertiary hospitals were included in this multicenter cohort study (October 2009 to March 2024). Patients were categorized into UA and DA groups based on the decisions of multidisciplinary teams. UA consisted of microwave ablation followed by adjuvant systemic therapy administered within 1 month. DA involved neoadjuvant systemic therapy (delivered over 2-3 months) combined with subsequent ablation. The primary outcome was progression-free survival (PFS), and a secondary outcome was overall survival (OS), both assessed using multivariable-adjusted Cox regression analysis and Kaplan-Meier survival curves. Procedure-related complication rates were analyzed. Sensitivity analyses, including propensity score matching, inverse probability treatment weighting, and overlap weighting, were performed to adjust for confounders. Results A total of 1047 patients were included (DA group [<i>n</i> = 536]: mean age, 57.53 years ± 10.99 [SD]; 381 male; UA group [<i>n</i> = 511]: mean age, 60.96 years ± 11.77; 356 male). The follow-up duration was 15 years. Median PFS (1.48 vs 0.98 years; hazard ratio [HR], 0.70 [95% CI: 0.61, 0.81]; <i>P</i> < .001) and OS (6.94 vs 4.74 years; HR, 0.70 [95% CI: 0.57, 0.87]; <i>P</i> = .001) were longer in the UA group compared with the DA group. Sensitivity analyses confirmed robustness (PFS HR, 0.67-0.80; OS HR, 0.73-0.77). UA benefits persisted across subgroups, including synchronous metastases (HR, 0.67 [95% CI: 0.55, 0.81]; <i>P</i> = .04) and lesions smaller than 3 cm (HR, 0.68 [95% CI: 0.58, 0.80]; <i>P</i> = .005). Elevated carcinoembryonic antigen levels (≥5 µg/L) and multiple metastases independently predicted worse survival (HR, 1.30 and 1.47, respectively; <i>P</i> < .001 for both). Conclusion UA combined with systemic therapy significantly improved long-term survival compared with DA, with similar complication rates. © RSNA, 2026 <i>Supplemental material is available for this article.</i> See also the editorial by Woodrum in this issue.