Selection of patients for resection of hepatic colorectal metastases: expert consensus statement.

Surgical margin status has been shown to be important in long-term outcomes following resection of colorectal liver metastases. Multiple studies have shown that a negative resection margin decreases local recurrence rates and improves survival.1,62 In a study by Scheele et al.,63 the median survival of patients who underwent an R1 or R2 resection was only 14 months compared with 44 months for those who underwent an R0 resection. In a more recent study by Choti et al.,1 patients who had a positive microscopic resection margin had a median survival of only 24 months compared with 46 months for patients with a negative surgical margin. In this study, positive surgical margin status was associated with a 3.5 increase in relative risk of disease-specific death. Similarly, Pawlik et al.62 reported that a positive resection margin was associated with a significantly higher risk of surgical margin recurrence and decreased overall survival. Given the importance of a clear surgical margin, the question then arises as to what constitutes a minimally acceptable negative microscopic margin. Several earlier series concerning liver resection for hepatic colorectal metastases have reported that one should attain at least a 1-cm margin,64,65 and if not possible, this should be a relative contraindication to surgery.66 Cady et al.65 reported that a surgical margin less than 1 cm was associated with a significantly shorter disease-free survival. As a result, many centers adopted the “1-cm rule” as a minimal margin to obtain at the time of hepatic resection.67,68 These findings, however, have not been corroborated in multivariate regression analyses adjusted for other confounding risk factors.62 In fact, other investigators62,69 more recently reported that the actual width of the surgical margin has no effect on survival as long as the margin is microscopically negative. Altendorf-Hofmann and Scheele69 noted that while patients with a microscopically positive margin had a worse prognosis compared with patients who had a microscopically negative margin, survival was not associated with the width of the negative surgical margin. Similarly, Pawlik et al.62 noted that the width of a negative surgical margin did not affect survival, recurrence risk, or site of recurrence following hepatic resection of colorectal metastases. In this study, patients with a positive surgical margin had a higher overall risk of recurrence (51%) compared with patients who had a negative surgical margin (40%); however, patients with a negative margin—regardless of the width of the surgical margin—had similar overall recurrence rates. The 5-year survival rate was 17% for patients with a positive surgical margin compared with 64% for patients with a negative surgical margin. The width of the surgical margin did not significantly affect survival in patients with negative margins.62 In the past, resection of hepatic colorectal metastases was not attempted in patients who had more than three or four metastases, hilar adenopathy, metastases within 1 cm of major vessels such as the vena cava or main hepatic veins, or extrahepatic disease. Earlier studies that established certain clinicopathologic factors as being contraindications for surgery have subsequently been criticized on both clinical and methodologic grounds. Methodologically, these studies were problematic because only a small number of patients who actually met all the “exclusion” criteria were included in the analyses. Additionally, most early studies reported only univariate or log-rank analyses while failing to control for competing risk factors. Clinically, data are problematic because many of these early studies were carried out prior to the era when new, more active chemotherapy agents, as well as new techniques such as portal vein embolization (PVE) and radiofrequency ablation, were available. More recent studies demonstrate that patients with “traditional” adverse clinicopathologic factors can achieve long-term survival following hepatic resection and therefore should not be excluded from surgical consideration. This has therefore precipitated a shift in the definition of resectability from criteria based on the characteristics of the metastatic disease (tumor number, size, etc.) to new criteria based on whether a complete (margin-negative) resection of the liver lesion can be performed. Currently, hepatic colorectal metastases should be defined as resectable when it is anticipated that disease can be completely resected, two adjacent liver segments can be spared, adequate vascular inflow and outflow and biliary drainage can be preserved, and the volume of the liver remaining after resection (i.e., the “future liver remnant”) will be adequate (at least 20% of the total estimated liver volume).21,70 This definition of resectability represents a paradigm shift. Instead of resectability being defined by what is removed, decisions regarding resectability should now focus on what will remain following resection. Concern for the future liver remnant is particularly pertinent during preoperative evaluation of patients for an extended hepatectomy (resection of ≥ five liver segments), as some patients may be excluded from the benefit of a potentially curative resection because the anticipated liver remnant may be too small. In general, 20% of the total liver volume appears to be the minimum safe volume that can be left following extended resection in patients with normal underlying liver. CT or MRI can now provide an accurate, reproducible method for preoperatively measuring the volume of the future liver remnant.70 To avoid operating on patients with low-volume future liver remnants, any patient who fails to show compensatory hypertrophy as a result of tumor growth and who has a future liver remnant of less than 20% should be considered for PVE to induce hypertrophy of the contralateral liver lobe.71 Another factor that has almost universally been well accepted as a contraindication to liver resection is the presence of extrahepatic disease. In Adson’s38 initial report in 1984, he noted that no patient with extrahepatic disease survived beyond 5 years. As such, extrahepatic disease has long been regarded as an absolute exclusion criteria for hepatic resection. The advent of more effective systemic chemotherapy agents, as well as improvements in imaging modalities to more accurately identify the true extent of extrahepatic disease, has prompted some investigators to advocate for surgical resection for patients with extrahepatic disease. Elias et al.72 have reported that the 5-year survival rates following hepatectomy for hepatic colorectal metastases and simultaneous resection of extrahepatic disease with curative intent was 29%. As such, the presence of extrahepatic disease should not be considered an absolute contraindication to hepatic resection. However, patients with extrahepatic disease must be selected carefully. In general, resection should only be considered following documentation of stable/responsive disease after treatment with systemic chemotherapy in situations where complete (margin-negative) resection is feasible. Management of patients with simultaneous intra- and extrahepatic disease involves complex clinical decision making and therefore should be carried out in a multidisciplinary setting. Consensus Statement: 1. In patients undergoing liver resection for hepatic colorectal metastases, a positive surgical margin is associated with a higher local recurrence and worse overall survival and should be avoided whenever possible. 2. While a wide (> 1-cm) resection margin should remain the goal when performing a liver resection, an anticipated margin of less than 1 cm should not be used as an exclusion criterion for resection. 3. Assessment of resectability of hepatic colorectal metastases should focus on the ability to obtain a complete resection (negative margins). 4. The feasibility of hepatic resection should also be based on three criteria related to the remaining liver following resection: (1) the ability to preserve two contiguous hepatic segments, (2) preservation of adequate vascular inflow and outflow as well as biliary drainage, and (3) the ability to preserve adequate future liver remnant (> 20% in a healthy liver). 5. The presence of extrahepatic disease should no longer be considered an absolute contraindication to hepatic resection provided the patient is carefully selected and a complete (margin-negative) resection of both intra- and extrahepatic disease is feasible.