Heterogeneous radiological response to neoadjuvant therapy is associated with poor prognosis after resection of colorectal liver metastases

Introduction: Surgery combined with perioperative chemotherapy has become standard of care in patients with resectable colorectal liver metastases. However, poor outcome is expected for a significant subgroup. The clinical implications of inter-metastatic heterogeneity remain largely unknown. In a prospective, population-based series of patients undergoing resection of multiple colorectal liver metastases, the aim was to investigate the prevalence and prognostic impact of heterogeneous response to neoadjuvant chemotherapy. Materials and Methods: Radiological response to treatment was evaluated in a lesion-specific manner in 2–5 metastases per patient. Change of lesion diameter was evaluated and response/progression was classified according to three different size thresholds; 3, 4 and 5 mm. A heterogeneous response was defined as progression and response of different metastases in the same patient. Results: In total, 142 patients with 585 liver metastases were examined with the same radiological method (MRI or CT) before and after neoadjuvant treatment. Heterogeneous response to treatment was seen in 16 patients (11%) using the 3 mm size change threshold, and this group had a 5-year cancer-specific survival of 19% compared to 49% for patients with response in all lesions (p = 0.003). Cut-off values of 4–5 mm were less sensitive for detecting a heterogeneous response, but the survival difference was similar and significant. Conclusion: A subgroup of patients with multiple colorectal liver metastases had heterogeneous radiological response to neoadjuvant chemotherapy and poor prognosis. The evaluation of response pattern is easy to perform, feasible in clinical practice and, if validated, a promising biomarker for treatment decisions.