Stage III colon cancer at Baylor University Medical Center at Dallas and the Baylor Sammons Cancer Center: experience from 2000 to 2004.

Colon cancer remains a major cause of cancer-related morbidity and mortality. In the USA, it is estimated that 106,680 new cases will be diagnosed and that 55,170 deaths will be attributed to the disease in 2006 (1). The stage of disease at the time of diagnosis is the single most important factor for predicting survival from the disease. In early stages, colon cancer is eminently curable, with expected 5-year survival rates of 90% or better. However, if the disease is more advanced at the time of diagnosis, the outlook is not nearly as favorable. In patients with advanced or metastatic disease at presentation, the chance of 5-year survival drops below 10% (2). Colon cancer is often asymptomatic or minimally symptomatic in the early stages of the illness, especially when the malignancy arises within the right side of the bowel. With appropriate screening, however, the disease can be discovered in the precancerous stage or in the earlier stages of cancer, when appropriate management offers an improved likelihood of cure. Unfortunately, studies have documented a low overall compliance with recommendations for colon cancer screening in the USA (3). Ongoing research continues to focus on understanding the obstacles to screening and improving compliance. At the time of diagnosis, clinical evaluations including physical examination and radiographic studies can determine if the colon cancer has spread beyond the regional tissues and lymph nodes. Seventy-five percent of patients are diagnosed before such spread, and in those patients surgical resection remains the mainstay of curative therapy. Analysis of the surgical specimen provides critical information regarding the pathologic stage of the cancer. In colon cancer, the stage is determined by the depth of invasion of the tumor through the bowel wall (T stage), the presence of local lymph node involvement (N stage), and the presence of distant spread or metastasis (M stage). Patients who have evidence of tumor in the local lymph nodes but no signs of additional spread are categorized as stage III. Recently, three additional substages (IIIa, IIIb, and IIIc) have been applied to this group of patients, reflecting the heterogeneity in prognosis seen among these patients (4). The role of postoperative or adjuvant chemotherapy has been clearly established in patients with surgically resected stage III colon cancer. Several large randomized trials have repeatedly demonstrated the benefits of this treatment, and in 1990 the National Institutes of Health Consensus Conference recommended adjuvant chemotherapy for all patients with stage III colon cancer (5). One of the first trials to unequivocally demonstrate the advantages of adjuvant chemotherapy for patients with stage III colon cancer was Intergroup Trial 0035 (6), which demonstrated a significant reduction in the rates of cancer recurrence as well as a significant improvement in the survival rates of patients who were randomly assigned to receive 1 year of postoperative 5-fluorouracil (5-FU)–based chemotherapy. Since that publication, several trials have reported similar findings (7–9). Newer chemotherapy agents have been studied in an effort to add to the convenience and efficacy of adjuvant therapy in patients with stage III colon cancer. Two such agents—capecitabine (10, 11) and oxaliplatin (12, 13)—were shown to be effective in stage IV colorectal cancer and were then tested in patients with stage III disease. Capecitabine, an orally administered prodrug that is converted to the active cytotoxic agent 5-FU, was studied as postoperative therapy in patients with stage III colon cancer in the X-ACT trial: 1987 patients were randomly assigned to receive 5-FU plus leucovorin administered intravenously for 6 months or capecitabine administered orally for 6 months. The two regimens were equivalent in their efficacy, with the toxicity profile and convenience of administration favoring the orally administered capecitabine (14). The combination of oxaliplatin with infusional 5-FU and leucovorin, a therapeutic regimen known as FOLFOX, was studied in patients with stage III colon cancer in the large MOSAIC trial. European investigators demonstrated a better cancer-free survival rate in patients treated with FOLFOX than in those treated with 5-FU plus leucovorin alone (15). Another trial from the National Surgical Adjuvant Breast and Bowel Project involved 2407 patients with stage II or III colon cancer who were randomly assigned to postoperative treatment with standard 5-FU and leucovorin alone or the same regimen of 5-FU and leucovorin plus oxaliplatin. Again, the patients in the oxaliplatin group experienced a better 3-year cancer-free survival rate than those assigned to treatment with 5-FU and leucovorin alone (78% vs 73%) (16). The findings of this trial have confirmed the additional benefits of oxaliplatin in the treatment of patients with stage III colon cancer.