Colorectal cancer with synchronous liver metastases

At the time of diagnosis, 15–20 per cent of patients with colorectal cancer have synchronous liver metastases. Synchronous metastases may confer a poorer prognosis than metachronous metastases but this is uncertain1. In any event, effective treatment requires an overall strategy that addresses both the primary and the metastatic disease, paying attention to optimal timing between surgical and medical interventions. Modern chemotherapy and stents for subocclusive tumours add further complexity. Strategy is generally influenced by two criteria: the symptom pattern of the primary tumour and the potential resectability of the liver metastases. Certain clinical presentations are clear indications for immediate surgical treatment of the primary tumour – notably occlusion, perforation, bleeding and locally advanced disease. Patients are usually elderly and ill, and the increased operative risks render a major one-stage procedure (resection of both primary and hepatic lesions) unwise. This contrasts with an asymptomatic primary tumour when management depends on the resectability of the liver metastases. In the asymptomatic setting, resection of synchronous liver metastases along with the primary lesion is warranted simply because this is the sole strategy with curative potential – a 5year survival of 25 to 38 per cent2–4. But should patients be treated initially by operation or by neoadjuvant chemotherapy? No randomized trial is yet available to answer this question directly, but a retrospective study examining outcomes in patients with more than four liver metastases suggests that neoadjuvant chemotherapy plus surgery offers a better survival than immediate operation5. A similar trend occurs in the LiverMetSurvey analysis of an international registry of patients operated for hepatic colorectal metastases. This shows that, while neoadjuvant chemotherapy does not improve outcome after resection of a single liver metastasis, it is associated with improved survival when more than four metastases are removed. While it seems logical that multinodular disease is likely to respond well to neoadjuvant chemotherapy because of a greater probability of undetected small metastases, this hypothesis deserves further scrutiny. In current practice, immediate surgery is the standard treatment for patients with few metastases, but neoadjuvant chemotherapy followed by surgery may be appropriate for those with multinodular disease. Combining hepatic with colorectal resection has the appeal of a single operation, which may be beneficial in terms of quality of life and cost. Contraindications are based on the risk of morbidity and mortality, and include emergency indication for operation on the primary tumour, a locally advanced colorectal tumour, and the need for a major hepatectomy (involving three or more segments). Otherwise, combined resections seem appropriate2–4. An alternative is colorectal resection with hepatic resection delayed for 2–3 months, with chemotherapy in between. It has been argued that combined resection may decrease the risk of metastatic spread by avoiding the repetitive immunosuppression of major surgery and by facilitating the efficacy of chemotherapy6. Delayed hepatic resection, however, is the preferred approach of those who believe that a period of observation allows better selection of those likely to benefit from liver surgery7. The choice may depend on the experience of the surgical team. Any decision must also consider the extent of the hepatectomy. Although there is no increase in operative mortality for one-stage procedures involving limited hepatectomies (one or two segments), a large study suggests this may not be so when a hepatectomy of three or more segments is required1. Consistent with these data, most initial work with one-stage procedures has restricted this strategy to patients with right colon cancer and a limited number of liver metastases2–4. Unfortunately, such restriction allows less than half of the eligible patients with synchronous metastases to be treated with a single operation. Such a narrow policy has recently been challenged – experienced groups are now reporting similar mortalities with one-stage and two-stage strategies that include major hepatectomies8. These reports also indicate that the one-stage approach has the benefit of a shorter hospital stay9. Long-term survival must also be considered. Most advocates of a onestage approach report survival results similar to those obtained with delayed hepatectomy2,3. However, as onestage procedures have usually been offered only to patients with limited metastatic disease, true equivalency