ReviewExtending the frontiers of resectability in advanced colorectal cancer
Introduction
Colorectal cancer is the third most prevalent malignancy in the world, and approximately 20% of patients develop isolated hepatic metastases.1 In these patients, the extent of liver disease is the main determinant of survival. The outcome of untreated hepatic metastases is dismal, with median survival of 5–12 months.2, 3 Hepatectomy is the only potentially curative therapy for colorectal liver metastases (CRLM), but when traditional criteria for resectability were used, only 10% of patients were candidates for surgical resection.4 Over the last decade, improvements in surgical technique, imaging, and systemic therapy have increased the number of patients eligible for curative liver resection. Innovative strategies to improve resectability of CRLM have emerged from multidisciplinary planning and treatment. Currently, resectability is defined as the ability to achieve a margin-negative resection while preserving more than 20% of the total estimated liver volume, sparing two contiguous hepatic segments, and maintaining adequate biliary drainage and vascular inflow and outflow.5 Despite expanding the criteria of resectability, the 5-year survival rate after resection of CRLM has improved from a historical rate of 25% to current rates ranging between 40% and 58%.4, 6, 7 This review outlines the strategies that have increased the number of patients eligible for potentially curative resection of CRLM including refutation of old criteria of resectability and introduction of treatment strategies such as neoadjuvant chemotherapy, preoperative volumetry, portal vein embolization, and two-stage hepatectomy.
Section snippets
Prognostic factors
Many studies have examined factors associated with outcome after hepatectomy for CRLM, including tumor number and size, width of tumor-free margin, and extrahepatic disease. While previous studies have demonstrated worse prognosis associated with greater number and size of metastases, narrower tumor-free margins, and presence of extrahepatic disease, more recent studies show that long-term survival is still possible despite the presence of one or more of these factors. Now, in many institutions
Systemic therapy
The diminishing significance of traditional criteria for resectability on patient outcome in CRLM is partly due to advances in modern chemotherapy. Over a decade ago, 5-fluorouracil (5-FU) was the sole chemotherapy used for colorectal liver metastases and yielded response rates of 20% with no improvement in survival. However, advances in chemotherapeutic agents and delivery have changed the treatment of CRLM dramatically (Fig. 1). Capecitabine was the first oral agent approved for use in
Future liver remnant and portal vein embolization
An absolute contraindication to liver resection is inadequate remnant functional liver parenchyma after resection, leading to hepatic failure. Various tools have been devised to predict the functional remnant liver. These include biochemical tests based on hepatic clearance of compounds, used commonly in Asia, and volumetric studies based on computed tomographic (CT) volumetry. Biochemical tests such as indocyanine green clearance are valuable for predicting morbidity and mortality in patients
Two-stage hepatectomy
Two-stage hepatectomy consists of a sequential strategy for bilobar, multinodular disease that cannot be resected in a single procedure. The first-stage involves a minor resection of metastases in the FLR, followed by a period of liver regeneration and PVE if indicated. The second-stage is performed 2–3 months later in the absence of significant tumor progression and consists of a major hepatectomy. Chemotherapy generally is administered before the first-stage and after the second-stage
Conclusions
This review shows that many patients excluded from curative resection in the past on the basis of traditional criteria of resectability may now be eligible for curative surgery if a multimodal approach is used. This includes strategies such as neoadjuvant chemotherapy, which diminishes or limits the tumor burden, and preoperative PVE, which increases the remaining liver volume. With these strategies, many patients with CRLM that would have been considered unresectable a decade ago are now
Conflicts of interest
None declared.
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