Downstaging or Downsizing: Time for a New Staging System in Advanced Colorectal Cancer?

Ten years ago, the management of advanced colorectal cancer was relatively straightforward. For the fortunate few with liveronly disease who managed to find their way to a liver surgeon and who met the stringent criteria of the day for hepatectomy (one to three unilobar metastases, preferably presenting metachronously, and resectable with a generous margin of healthy liver tissue), there was the chance of surgery with curative intent. If they survived the surgery, the patients had a 30% to 40% chance of being alive 5 years later. However, these patients accounted for less than 10% of all patients with advanced liver-only disease, and for patients with nonresectable disease, the chance of being alive 5 years after diagnosis was less than 1%. Palliative chemotherapy using fluorouracil and leucovorin achieved a measurable response in barely 20% of patients and improved median survival time from 8 months with best supportive care to little over 12 months. At that time, the American Joint Committee on Cancer staging system for advanced colorectal cancer was equally straightforward; all patients with metastatic disease beyond the immediate lymph node basin of the primary tumor had stage IV disease, and their prognosis was grim. The situation in 2006 has changed completely for both resectable and unresectable patients. Over the last 10 years, the definition of resectability has evolved, overcoming the morphologic limitation used in the past as selection criteria. Now the definition of resectability with curative intent is the ability of the surgeon to clear, with negative margin, all measurable disease from the liver while leaving a healthy future remnant liver of 20% of the total liver volume. Factors that determine the extent of safe liver resection include performance status and concurrent parenchymal liver disease. Liver resection is now considered selectively in some subsets of patients with limited resectable extrahepatic disease. Hilar lymph node metastases; lung, ovarian, and adrenal metastases; and local or regional recurrence are no longer formal contraindications.