Surgical management of colorectal liver metastases—a practical clinical approach

Although surgery poses the only potential treatment strategy for long-term survival and cure in patients with CRLM, not every patient is amenable for surgical resection [1]. Thorough patient selection within the multidisciplinary conference as early as at the time of disease diagnosis is crucial (Fig. 1). The following key components should be taken into account during the evaluation process:

In general, colorectal liver metastases can be divided into three subgroups: resectable, borderline or potentially resectable (after downsizing), and unresectable. Of note, a patient’s resectability should always be defined by the purposes of treatment planning, as surgery for CRLM is always performed with curative intent. As already mentioned earlier, the surgical strategizing eventually revolves around the question of whether complete removal of the metastatic lesions is achievable while preserving a functional future liver remnant (FLR). In case the FLR is not sufficient, the patient might develop post-hepatectomy liver failure (PHLF), a serious postoperative complication associated with high morbidity and mortality [6]. In addition, the following aspects should also be kept in mind when assessing resectability: disease burden (size, number, location of CRLM) [7, 8], disease biology (progression during systemic therapy, suspected extrahepatic metastases, primary tumor sidedness, metachronous vs. synchronous CRLM development, mutational status, presence of microsatellite instability) [9, 10], and technical considerations such as relationship to the vascular inflow/outflow and biliary system [11].

Importantly, several factors such as liver cirrhosis, steatosis hepatis, and chemotherapy-associated liver injuries (CALI) might diminish the liver’s regenerative capacity. Therefore, the target FLR is directly dependent on the quality of the non-metastatic liver parenchyma. Current guidelines propose an FLR of minimum 20–25% in healthy hepatic tissue, 30% in patients with chemotherapy-associated liver injury, and 40% in cirrhotic liver [12].

Only 10% of CRLM cases are deemed resectable upfront, where sufficient remnant liver can be left behind after complete removal of all liver metastases (Table 1). 20% of CRLM patients have borderline resectable disease, in which a conversion therapy (5-fluorouracil-based triplet or doublet chemotherapy in combination with a targeted agent) is indicated due to metastatic invasion into preservable vascular structures, thus making tumor downsizing necessary first, in order to achieve negative margins following surgery. The remaining 70% of CRLM patients suffer from unresectable disease, where factors such as multiple disease sites, infiltration of metastases into all liver segments, or a poor patient performance status render resection unfeasible. As a result, the patient will initially undergo so-called palliative systemic therapy but should be reevaluated for potential resectability after 2–3 months [13].

The optimal timing and treatment sequencing when treating patients with synchronous colorectal liver metastases must be discussed in a multidisciplinary setting involving chemotherapy/chemoradiotherapy (for patients with primary rectal cancer), surgery, and maybe other forms of locoregional treatment. Depending on the acuity of symptoms and disease burden, the sequence of surgical resection of the primary tumor and liver metastases can vary [14]. For instance, patients who present with symptoms from the primary colorectal cancer (i.e., bowel obstruction, bleeding, and perforation) will require resection of the primary tumor first. In contrast, if the patient is asymptomatic from his primary tumor and suffers from multiple bilobar metastases, then the liver-first approach is the gold standard, as it is associated with a more favorable prognosis [15]. Finally, the simultaneous approach, which involves resection of the primary tumor and liver metastases during one surgical procedure, should be reserved for patients with a good performance status and limited hepatic disease. Major hepatic surgery combined with removal of the primary tumor may be prone to postoperative complications such as anastomotic leakage [15, 16]. Figure 2 provides an outline of a possible treatment algorithm for synchronous CRLM.

With the development of various novel operative techniques, several surgical strategies can currently be followed for treatment of CRLM. The main goal of resection remains the complete removal of all macroscopic hepatic metastases, while leaving a sufficient FLR behind. In this regard, the following surgical interventions should be mentioned:

While parenchymal-sparing hepatectomy follows the idea of preserving as much non-tumorous liver tissue as possible, it is still considered to be oncologically equivalent to anatomic liver resections [18]. The concept of preoperative double-vein embolization (portal vein and hepatic vein embolization) is based on the induction of hypertrophy in the future liver remnant (FLR). Especially in patients with a small FLR, double-vein embolization of the diseased lobe can result in augmentation of the FLR, thus facilitating curative resection at a later timepoint (usually 2–6 weeks) [19]. In addition, the principle of two-stage hepatectomy consists of two liver resections, where during the first surgery a tumor clearance from the planned FLR is performed. Subsequently, the contralateral portal vein is ligated or embolized, in order to induce hypertrophy of the FLR. Once this has been achieved, the remaining tumor burden will be resected during the second surgery [20]. Lastly, the so-called ALPPS procedure is a variant of two-stage hepatectomy. Similar to the conventional strategy, the first operation aims at clearing all tumor mass from the FLR. Following this, the contralateral portal vein is ligated and the liver is divided along the intended transection line without destroying the remaining vascular and biliary pedicles of the FLR. After sufficient FLR augmentation has been accomplished, the remaining hepatic metastases are removed during the second stage, mostly extended liver resection [21].