New Developments in the Adjuvant Therapy of Stage II Colon Cancer

While adjuvant chemotherapy has proven benefit in stage III colon cancer, its role for stage II colon cancer remains unclear. This article reviews data regarding adjuvant therapy in stage II colon cancer. We will discuss factors to consider in assessing the risk of recurrence in stage II disease. We will also outline considerations regarding adjuvant therapy in older patients.

Colon cancer is estimated to have accounted for 106,100 new cancer cases and 49,920 cancer-related deaths in 2009.[1] Over half of these new diagnoses and deaths occur in individuals age 70 and older.[2] The probability of developing colon cancer increases with advancing age from less than 1% in the first 4 decades of life to nearly 5% in the seventh decade of life [2]. Nearly 40% of these older individuals are diagnosed with stage II disease [2]. While the overall 5-year survival rate for individuals 75 and older is 67% for all stages of colon cancer, survival of those aged 70 to 79 diagnosed with stage II (T3 or T4, N0, M0) colon cancer is 77% (low-grade disease) or 70% (high-grade disease).[2,3]

The benefit of adjuvant chemotherapy after surgery for stage III colon cancer is well established.[4,5] However, the role of chemotherapy in patients with stage II disease not as well established and has been a source of debate over the past 2 decades. While the percentage of stage II colon cancer patients of any age that receive adjuvant therapy after surgery is unknown, one study found that 27% of 65- to 75-year-old Medicare beneficiaries received chemotherapy for stage II disease.[6] This article will outline the evidence for chemotherapy in stage II colon cancer and review risk assessments for colon cancer recurrence, with a focus on older patients.

Treatment Efficacy-Fluoropyrimidine Monotherapy

Early studies in adjuvant colon cancer enrolled patients with stage II and III disease.[7-11] The North Central Cancer Treatment Group (NCCTG) and subsequently the Eastern Cooperative Oncology Group (ECOG) compared the administration of fluorouracil (5-FU) and levamisole with observation in the adjuvant setting.[10,11] The NCCTG trial enrolled 401 patients with stage II or III colon cancer and demonstrated a 31% reduction in recurrence rate for patients with stage III disease who received fluorouracil and levamisole.[10] In the larger ECOG trial of 1,296 patients, adjuvant fluorouracil and levamisole reduced the risk of recurrence by 41% (P = .0001) and the risk of death by 33% (P = .006) compared with surgery alone in patients with stage III disease.[11] In contrast, no meaningful benefit was noted in the subset of patients with stage II disease.

TABLE 1

Pooled Analyses of Randomized Clinical Trials of Fluoropyrimidine Adjuvant Therapy for Stage II Colon Cancer

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