Locoregional surgical and interventional therapies for advanced colorectal liver metastasis: expert consensus statement

The expert panel of hepatobiliary surgeons has presented an expansive and comprehensively thought out review on a number of key issues that continue to challenge the oncology community, especially regarding which of the various local or regional therapies are optimal and their best timing in patients with colorectal cancer and liver metastasis.¹ The authors have expertly broken these challenges into four key areas: approaches to bilateral colorectal liver metastasis; approaches to synchronous presentations of colorectal cancer and liver metastasis; intra-arterial therapies, and ablation strategies that include the use of radiofrequency and microwave technology and external beam radiotherapy.¹ These topics are reviewed to varying extents and key consensus statements given at the end of each section to provide further guidance in the management of colorectal liver metastasis.

The optimal approach and timing in the surgical therapy of patients with bilateral colorectal liver metastasis remain challenging because of the substantial heterogeneity among patients in this group. Clear consensus indicates that the ability to remove all metastatic deposits, leaving an adequate liver remnant, is key to the underlying definition of resectability.² Variables that confound this definition include the presence of significant underlying comorbidity in the patient, the timing of the patient's referral based on the extent of chemotherapy that has been administered, the underlying bias of the referring medical oncologist and, lastly, the underlying desire of the patient, predominantly based on his or her overall goals and understanding of the overall outlook for survival.

One-stage hepatectomy optimizing the parenchyma-sparing techniques of either resection or ablation is an evolving technique that can be used in patients with bilateral colorectal metastasis for multiple reasons; these include the technique's facility to allow the avoidance of a second operative procedure and to ensure that any interruption of chemotherapy is minimized. As the authors have highlighted, the incidence of recurrence in patients with bilateral colorectal metastasis is high, even when complete resection has been achieved.¹ This high level of recurrence is strongly acknowledged by the medical oncology community and thus reducing the overall duration of interruption of chemotherapy remains a goal. Hypothetically, a one-stage operation might beneficially address local liver-specific progression and even overall progression. Any continued interruption of therapy should not exceed 12 weeks, which should include a 4-week period prior to hepatectomy and a 6–8-week recovery period after hepatectomy. Based on these criteria, one-stage hepatectomy aimed at achieving optimal lesion control through the complete resection and/or ablation of all disease should and can be considered. The authors suggest a very conservative ablation diameter of ≤ 1 cm, a standard that has been disproven in a number of key ablation articles.¹ Other experienced surgeons utilizing high-quality intraoperative ultrasound have shown that lesions measuring < 3 cm in size can be treated successfully with up-to-date ablation modalities and outcomes similar to those obtained in wedge resection or sub-segmental resection can be achieved.^3–6 Thus, consideration should be given to methods of optimizing a one-stage technique using resection or ablation alone or a combination of these under the appropriate circumstances.

Appropriately, and with initial enthusiasm, the authors mention the continued evaluation of the use of intra-arterial therapies to downsize metastasis.¹ A large amount of safety data derived from patients who have undergone hepatectomy following yttrium-90 radioembolization and drug-eluting bead therapy or a combination of these is available from a number of high-volume institutions.^7–9 Hepatectomy performed at least 4–6 months after radioembolization or drug-eluting bead therapy appears to be safe. Similarly, hepatectomy after prior intra-arterial therapy appears to be safe.⁹ Thus, patients in whom disease has been downsized by such intra-arterial therapies should undergo evaluation for surgical treatment of all known disease.

The optimal approach to synchronous presentations of colorectal and liver metastases has been well established and continues to evolve through the three different surgical strategies outlined in the consensus paper.¹ The respective benefits and efficacies of the ‘simultaneous’, ‘colorectal first’ and ‘liver first’ approaches have each been demonstrated in the appropriate setting based on individual patient characteristics. The advent of minimally invasive hepatectomy contributes further to the consideration of timing and extent of resection.^10–13 Recent reports from a number of large institutions have demonstrated the possible advantages to be derived from the use of laparoscopic hepatectomy in patients with colorectal liver metastasis, predominantly in the reduction of adverse events and overall length of stay, as well as in overall improvements in quality of life.¹⁴

The authors have appropriately reviewed the use of hepatic–arterial infusion (HAI) therapy and clearly state that surgeon technique and volume are key components to the delivery of successful HAI therapy.¹ It should be emphasized that an additional key to the success of HAI therapy is the medical oncologist.^15,16 The complexity of patient management and the apparently limited overall benefit to be derived from this therapy outwith the context of programmes with extensive experience have raised questions on its sustainability.¹⁷ Trial-based evidence of patient benefit is required prior to wider acceptance of this therapy and specialty expertise will remain mandatory for its successful implementation.

The consensus document addresses chemoembolization by combining conventional transcatheter arterial chemoembolization (TACE) and newer approaches using drug-eluting beads.¹ It should be noted that these are quite different therapies; they use different types of chemotherapy and catheter, and involve different arterial flow endpoints.¹⁸ Therapeutic TACE typically entails the delivery of chemotherapy with embolic flow stasis in the segmental artery of the treated lesion, whereas therapy with drug-eluting beads does not seek to induce stasis because in this context stasis tends to increase morbidity without increasing overall efficacy.^18,19

A further question regarding arterial embolization therapies refers to their timing in the sequence of multidisciplinary therapy for advanced colorectal liver metastases. Should intra-arterial therapy be considered after systemic chemotherapy failure or earlier in the sequence for an enhanced response? Is there even a role for arterial embolization in high-risk resectable disease in terms of improving recurrence-free survival? The consensus paper is not able to provide clear guidelines in this respect because data are not yet available and the field is rapidly evolving. First-line trials in unresectable liver only/liver-dominant colorectal liver metastasis with yttrium-90 (http://clinicaltrials.gov/ct2/show/NCT00724503) and drug-eluting bead therapy (http://clinicaltrials.gov/ct2/show/NCT00932438), and a trial of yttrium-90 as a second-line therapy (http://clinicaltrials.gov/ct2/show/NCT01483027) are currently enrolling. Progress in this area is therefore anticipated, but the issues involved will remain topics of major debate.

Conflicts of interest

RCGM receives research support from Biocompatibles. RS is a consultant for Nordion.