Improving Survival Rates by Surgical Resection of Colorectal Liver Metastases

Abstract & Commentary

By William B. Ershler, MD

Synopsis: In a retrospective analysis of aggressive two-stage hepatic resection of colorectal metastases, survival was 51% at 5 years compared to only 15% for comparable patients treated with chemotherapy alone. The complexity of the surgical approach and the advent of potentially more effective systemic therapies highlight the need for a definitive randomized trial before such an approach is assimilated into community practice.

Source: Brouquet A, et al. High survival rate after two-stage resection of advanced colorectal liver metastases: Response-based selection and complete resection outcome. J Clin Oncol 2011;29:1083-1090.

Advances in surgical oncology have resulted in new and more aggressive approaches to metastatic disease in certain clinical settings, such as for patients with colorectal cancer metastatic to the liver.1 One such advance is the two-stage resection (TSR),2 which has been shown in selected series to produce impressive survival rates.2-4 However, the generalizability of such an approach is under question because of concerns that the dramatically improved survival rates in operated patients compared to those treated with chemotherapy alone reflected a selection bias. That is, were patients selected for surgery those with more favorable prognostic features? Optimally, this would be addressed in a randomized clinical trial. However, short of that, the current report describes outcomes for well-matched patients treated at a single institution either with aggressive surgical resection of colorectal liver metastases (CLM) by the two-stage procedure or chemotherapy alone.

For this, data on patients undergoing resection were compared to matched patients receiving chemotherapy alone. Thus, the non-surgical patients had colorectal metastases with liver-only disease, a prior objective response to chemotherapy, and were alive 1 year after chemotherapy initiation. The investigators used intent-to-treat analysis. In the majority of patients who were candidates for and opted for TSR, the program included limited resection of CLM located in the left liver followed by right portal vein embolization 1 to 2 weeks later and then an extended right hepatectomy.

Sixty-five patients underwent the first stage of TSR; 62 patients fulfilled the inclusion criteria for the medical group. TSR patients had a mean of 6.7 + 3.4 CLM with mean size of 4.5 + 3.1 cm. Nonsurgical patients had a mean of 5.9 + 2.9 CLM with mean size of 5.4 + 3.4 cm (not significant). Forty-seven TSR patients (72%) completed the second stage of the procedure. Progression between stages was the main cause of non-completion of the second stage (61%). After 50 months median follow-up, the 5-year survival rate was 51% in the TSR group and 15% in the medical group (P = 0.005). In patients who underwent TSR, non-completion of TSR and major postoperative complications were independently associated with worse survival.

Commentary

It is clear from the data presented that TSR is associated with excellent outcome in patients with advanced CLM. Certainly, this is the result both of surgical resection and optimal patient selection. Those taken to surgery have demonstrable chemotherapy-induced tumor shrinkage, perhaps reflecting a "responsive" population. The authors are credited for making efforts to identify suitable controls with many of the same prognostic factors. However, the fact remains that for one reason or another these patients were treated differently, and it is not clear what factors led to the decision to operate on some and not on others. Could it be that those treated medically had more comorbidity or some other factor that would negatively influence prognosis?

Defining the role of surgical resection for CLM remains to be fully established, and of course this would best be accomplished by an appropriately randomized clinical trial. The data presented are provocative and provide substantial rationale for such a trial. This would be particularly important in light of the advances in systemic management of metastatic colorectal cancer with more effective chemotherapy (oxaliplatin and irinotecan) as well as monoclonal antibodies targeting vascular endothelial growth factor (bevacizumab) and epidermal growth factor receptor (cetuximab and panitumumab). Another variable worthy of consideration is the overall complexity of the two-step surgical procedure involving operating twice on an already diseased liver. Although the authors report a 6% 90-day mortality rate and a 50% morbidity rate after the second stage of the procedure, these figures are likely to be less optimal in the hands of less experienced surgeons.

Thus, the M.D. Anderson experience with two-stage resection of CLM is quite favorable but further study is warranted before such an approach is routinely undertaken in the community.

References

1. Abdalla EK, et al. Recurrence and outcomes following hepatic resection, radiofrequency ablation, and combined resection/ablation for colorectal liver metastases. Ann Surg 2004;239:818-825; discussion 825-827.

2. Wicherts DA, et al. Long-term results of two-stage hepatectomy for irresectable colorectal cancer liver metastases. Ann Surg 2008;248:994-1005.

3. Chun YS, et al. Systemic chemotherapy and two-stage hepatectomy for extensive bilateral colorectal liver metastases: Perioperative safety and survival. J Gastrointest Surg 2007;11:1498-1504; discussion 1504-1505.

4. Jaeck D, et al. A two-stage hepatectomy procedure combined with portal vein embolization to achieve curative resection for initially unresectable multiple and bilobar colorectal liver metastases. Ann Surg 2004;240:1037-1049; discussion 1049-1051.