Current Issues in Adjuvant Treatment of Stage II Colon Cancer

Abstract

Background: Adjuvant chemotherapy with 5-fluorouracil modulated by folinic acid, combined with oxaliplatin, has now become an accepted standard of care for patients with stage III colon cancer. In contrast, the use of adjuvant therapy for stage II patients remains controversial, and the identification of reliable prognostic factors to aid therapeutic decision making is crucial.Methods: The authors critically review the results of clinical trials and meta-analyses investigating the value of adjuvant chemotherapy for stage II patients, emphasizing the heterogeneous nature of this population and the difficulty of performing clinical trials with sufficient power to reliably assess treatment efficacy. They also discuss the evidence concerning potential prognostic factors, particularly molecular markers.Results: Available clinical trial data do not support the routine use of adjuvant chemotherapy for all stage II patients but suggest that it should be considered, particularly for certain high-risk patients. Recent guidelines advocate considering factors such as tumor differentiation, tumor perforation, number of lymph nodes examined, and T stage when assessing the likely benefit:risk ratio. Microsatellite instability and allelic imbalance seem to be strong predictors of good and poor prognosis, respectively, and in the near future, therapeutic decisionmaking models are likely to be further refined by the inclusion of such molecular markers.Conclusions: There is growing evidence that the prognosis of certain stage II patients with unfavorable prognostic factors can be improved by adjuvant chemotherapy, and increasingly refined tools are now available to define those most likely to benefit. Referral of stage II patients for individual assessment is strongly recommended.

Inequity in colorectal cancer treatment and outcomes: a population-based study

“…Randomised controlled trials suggest that chemotherapy may benefit stage II colon patients with poor prognostic features (Gill et al, 2004;Australian Cancer Network Colorectal Cancer Guidelines Revision Committee, 2005;André et al, 2006). These findings appear to have disseminated into routine practice, as those stage II patients in our study with more extensive tumours were significantly more likely to be treated.…”

“…was available. Such factors are likely to have determined treatment aggressiveness and survival, especially among stage II colon cancer patients, who comprise a particularly heterogeneous group (André et al, 2006).…”

“…However, some recent studies suggest that stage II patients with poor prognostic features (such as bowel perforation, involved lymph nodes, etc.) might benefit (Gill et al, 2004;André et al, 2006) and US and Australian guidelines advocate chemotherapy for this subgroup (Australian Cancer Network Colorectal Cancer Guidelines Revision Committee, 2005;NCCN, 2006a). For stage III colon cancer, RCTs suggest that best practice is surgery followed by chemotherapy (5-fluorouracil (5-FU) -leucovorin or capecitabine, and more recently supplementation with oxaliplatin) to improve survival (Cascinu et al, 2003;André et al, 2004a;Twelves et al, 2005).…”

Multimarker phenotype predicts adverse survival in patients with lymph node‐negative colorectal cancer

“…Reliable prognostic factors for high-risk, lymph node-negative CRC have yet to be elucidated and undoubtedly would improve therapeutic decision making. 25 In this study, the prognostic value of 13 potential tumor markers was evaluated in lymph node-negative CRC by IHC using a TMA. On the basis of our previous findings, 11 of these markers were identified as significant and independent prognostic factors in MMR-proficient CRC and, thus, were selected for the current investigation.…”

Methylation status in patients with early stage colon cancer: A new prognostic marker?

“…Yet, up to 30% of Stage II patients relapse within 5 years of surgery. 1 To date, there are no recommended pathological or molecular markers for predicting which Stage II patients are likely to relapse. 2 For this reason, we have read with utmost interest the article by Andersen et al 3 The authors investigated the association between genomic alterations (in terms of copy-number variations) and risk of recurrence in patients with Stages II and III CRC and identified a copy-number loss on chromosome 16 (16p13.2) that was predictive of metastatic recurrence in microsatellite-stable (MSS) Stages II and III CRCs.…”