Disappearing Colorectal Liver Metastases: Should the Treatment Sequence Be Reconsidered for Selected Lesions?

Disappearing liver metastases (DLMs) remain a challenging problem in the management of colorectal liver metastases (CRLMs). Although modern systemic therapy may produce complete radiological responses, radiological disappearance does not reliably indicate complete pathological response. Conversely, mandatory treatment of every original metastatic site may cause unnecessary parenchymal sacrifice when a lesion is no longer identifiable on hepatobiliary contrast-enhanced magnetic resonance imaging or intraoperative ultrasonography. Current strategies-including treatment of the presumed site, selective pre-treatment fiducial marking where feasible and considered appropriate, and structured surveillance-therefore involve important trade-offs. We propose a hypothesis-generating, lesion-specific strategy for a narrowly selected subgroup: thermal ablation before systemic therapy of one or a few small CRLM, preferably no larger than 2 cm, considered at higher anticipated risk of post-treatment loss of localization. Selection should distinguish the probability of radiological disappearance from its clinical consequences. Candidate lesions should be clearly and unambiguously identifiable on high-quality baseline imaging, safely accessible for ablation with a margin greater than 5 mm and ideally approximately 10 mm, and located outside any planned resection field, particularly when their depth or anatomical position would make empirical treatment difficult after disappearance. Recent randomized evidence supports thermal ablation as definitive local therapy for appropriately selected small CRLM but does not validate the proposed pre-systemic treatment sequence. This approach should not delay urgently required systemic therapy, compromise biological selection, or be used indiscriminately in high-volume, rapidly progressive, uncontrolled extrahepatic, or technically unsuitable disease. It is also generally unnecessary when the lesion is encompassed by a planned resection or total hepatectomy within a liver transplantation pathway. Upfront ablation may secure local control while the target remains visible, preserve liver parenchyma, and avoid premature interruption of systemic therapy or acceleration of surgery solely because a responding lesion is becoming radiologically occult. However, it may cause overtreatment and procedural morbidity and remains unsupported by prospective comparative evidence. A multicentre feasibility study, followed by prospective comparison with contemporary standard sequencing and, where feasible and considered appropriate, fiducial-based localization, is required to evaluate this strategy.