Up-Front Versus Delayed Thermal Ablation for Colorectal Liver Oligometastases: A Multicenter Retrospective Study Using Propensity Score Matching.

Abstract

<b>BACKGROUND.</b> Thermal ablation combined with systemic therapy is an accepted treatment of colorectal liver oligometastases (CLOM). Consensus is lacking regarding the optimal timing of thermal ablation relative to systemic therapy. <b>OBJECTIVE.</b> The purpose of our study was to compare delayed and up-front thermal ablation in terms of efficacy and safety in the treatment of patients with CLOM. <b>METHODS.</b> This retrospective multicenter study included 440 patients (316 men, 124 women; mean age, 57.1 ± 11.1 [SD] years) with CLOM from nine hospitals between October 2009 and December 2020. Patients underwent delayed (<i>n</i> = 322) or up-front (<i>n</i> = 118) thermal ablation in combination with systemic therapy. Analyses included all patients using crude data, all patients using inverse probability treatment weighting (IPTW), and a subset of patients using propensity score matching (PSM) at a 1:1 ratio to balance baseline variables (108 matched patients for each group [i.e., delayed ablation and up-front ablation]). Patients were classified as having a low or high tumor burden score (TBS) on the basis of the number and size of the liver metastases. The primary outcome was progression-free survival (PFS); secondary outcomes included overall survival (OS), complications from ablation, and adverse events (AEs) from systemic therapy. Survival analysis used the Kaplan-Meier method. <b>RESULTS.</b> The median follow-up was 2.9 years. The 5-year PFS was 17.1% for delayed ablation versus 33.6% for up-front ablation in all patients and 17.9% versus 34.7% after PSM. Delayed ablation was associated with worse PFS in the crude analysis (HR = 0.62), IPTW analysis (HR = 0.66), and PSM analysis (HR = 0.62) (all <i>p</i> < .05). No analysis showed a significant difference in OS between delayed and up-front ablation. Crude, IPTW, and PSM analyses showed better PFS for up-front compared with delayed ablation in patients with a low TBS (HR = 0.62-0.67; all <i>p</i> < .05); none of these analyses showed significant difference in PFS in patients with a high TBS. Delayed ablation and up-front ablation groups showed no difference in frequency of grade III or IV ablation complications (4.7% vs 6.8%, <i>p</i> = .38) or grade III or IV systemic therapy AEs (12.4% vs 10.2%, <i>p</i> = .53). <b>CONCLUSION.</b> In patients with CLOM, up-front ablation achieved better PFS compared with delayed ablation, although only among patients with a low TBS. <b>CLINICAL IMPACT.</b> These findings could help optimize clinical implementation of thermal ablation in patients who are not candidates for surgical resection.