André Thierry, Sargent Daniel, Tabernero Josep, O'Connell Michael, Buyse Marc, Sobrero Alberto, Misset Jean-Louis, Boni Corrado, de Gramont Aimery
Service d'Oncologie Médicale, Hôpital Tenon, 4 Rue de la Chine, 75970, Paris Cedex 20, France, and Vall d'Hebron University Hospital, Barcelona, Spain.
Ann Surg Oncol. 2006 Jun;13(6):887-98. doi: 10.1245/ASO.2006.07.003. Epub 2006 Apr 14.
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.
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.
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 decision-making models are likely to be further refined by the inclusion of such molecular markers.
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.
亚叶酸钙调节的5-氟尿嘧啶联合奥沙利铂的辅助化疗现已成为III期结肠癌患者公认的标准治疗方案。相比之下,II期患者辅助治疗的应用仍存在争议,确定可靠的预后因素以辅助治疗决策至关重要。
作者批判性地回顾了调查II期患者辅助化疗价值的临床试验和荟萃分析结果,强调了该人群的异质性以及开展有足够效力可靠评估治疗疗效的临床试验的难度。他们还讨论了有关潜在预后因素的证据,特别是分子标志物。
现有的临床试验数据不支持对所有II期患者常规使用辅助化疗,但表明应予以考虑,特别是对于某些高危患者。近期指南提倡在评估可能的获益风险比时考虑肿瘤分化、肿瘤穿孔、检查的淋巴结数量和T分期等因素。微卫星不稳定性和等位基因失衡似乎分别是预后良好和不良的有力预测指标,在不久的将来,治疗决策模型可能会通过纳入此类分子标志物而得到进一步完善。
越来越多的证据表明,某些具有不良预后因素的II期患者的预后可通过辅助化疗得到改善,现在有了越来越精细的工具来确定最可能获益的患者。强烈建议将II期患者转诊进行个体评估。