The challenge of disappearing colorectal liver metastasis: balancing considerations between tumor biology and clinical consequence for liver surgery.

The modern use of neoadjuvant and conversion systemic therapy in patients with colorectal cancer liver metastasis (CRLM) has improved resection rates and changed the borders between "resectable" and "unresectable" disease. Also, the use of preoperative systemic therapy has resulted in an increased frequency of disappearing liver metastasis (DLM). The optimal management of DLM is still controversial. In this review, we explore the current literature and highlight key findings relating to the tumor biology, diagnosis and treatment options of DLM. The definition of DLM should be based on hepatobiliary contrast MRI, which is the most sensitive preoperative imaging method. Patients with DLM are younger and more often have normalized their CEA-levels, and they have a better survival than those without DLM, likely reflecting favorable tumor biology and effective treatment response. Recent data indicate that molecular profiling (e.g. APC mutations) may predict CRLM at highest risk for vanishing after chemotherapy. However, just because the lesion has disappeared on imaging does not mean that there is a complete histopathological response. However a "watch and wait" strategy for patients with DLM is not associated with a reduced survival compared to resected DLM, but may be associated with a higher rate of recurrence often available for "rescue therapy", i.e. ablation or resection at the time when DLM recur and become visible. Furthermore, very few of "blind resections" of DLM contain viable tumor cells. International surveys among practicing hepatobiliary surgeons have revealed a widespread variation in the clinical management of DLM. In the future, biopsy and sequencing of metastases may be considered for therapeutic decision making in patients with CRLM considering the intricate tumor heterogeneity and clonal evolution of the disease.