Challenges in the management of stage II colon cancer.
Challenges in the management of stage II colon cancer.
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DOI：
10.1053/j.seminoncol.2011.05.005
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发表时间：
2011-08
影响因子：
4
通讯作者：
Cohen SJ
中科院分区：
文献类型：
--
作者：
Dotan E;Cohen SJ
大约三分之一的诊断为早期结直肠癌（CRC）的患者将出现淋巴结受累（III期），大约四分之一的患者出现透壁肠壁浸润但淋巴结阴性（II期）。辅助化疗靶向微转移性疾病，以提高无病生存率和总生存率。虽然对III期患者有益，但辅助化疗在II期患者中的作用尚未确定。这可能与这些患者的结局改善以及难以开展具有足够把握度的研究来记录该患者人群的获益有关。然而，最近的研究也表明，II期和III期癌症之间以及II期患者内部可能存在分子差异。经验证的病理预后标志物可用于确定II期患者复发的高风险，辅助化疗的获益可能更大。这些高风险特征包括较高的T分期（T4对T3）、次优淋巴结切除、淋巴血管浸润、肠梗阻或肠穿孔以及低分化组织学。然而，对于大多数不携带任何这些不良特征并被归类为“平均风险”II期患者的患者，辅助化疗的益处仍未得到证实。对II期结肠癌潜在生物学的新认识已经确定了可能改变这种模式并改善我们对II期疾病的风险评估和治疗选择的分子标记物。作为DNA错配修复系统功能标志物的微卫星稳定性评估已成为II期CRC患者风险分层的有用工具。具有高频率的微卫星不稳定性（MSI-H）的患者已被证明具有增加的总体存活率，并且从基于5 FU的化疗中获益有限。有必要进行更多的研究，以明确定义在常规临床实践中使用该标记物和其他标记物的最合适方法。
Approximately one-third of patients diagnosed with early stage colorectal cancer (CRC) will present with lymph node involvement (stage III) and about one-quarter with transmural bowel wall invasion but negative lymph nodes (stage II). Adjuvant chemotherapy targets micrometastatic disease to improve disease-free and overall survival. While beneficial for stage III patients, the role of adjuvant chemotherapy is unestablished in Stage II. This likely relates to the improved outcome of these patients, and the difficulties in developing studies with sufficient power to document benefit in this patient population. However, recent investigation also suggests that molecular differences may exist between stage II and III cancers and within stage II patients. Validated pathologic prognostic markers are useful at identifying stage II patients at high risk for recurrence for whom the benefit from adjuvant chemotherapy may be greater. Such high risk features include higher T stage (T4 versus T3), suboptimal lymph node retrieval, presence of lymphovascular invasion, bowel obstruction or bowel perforation, and poorly differentiated histology. However, for the majority of patients who do not carry any of these adverse features and are classified as “average risk” stage II patients, the benefit of adjuvant chemotherapy remains unproven. Emerging understanding of the underlying biology of stage II colon cancer has identified molecular markers which may change this paradigm and improve our risk assessment and treatment choices for stage II disease. Assessment of microsatellite stability which serves as a marker for DNA mismatch repair system function has emerged as a useful tool for risk stratification of patients with Stage II CRC. Patients with high frequency of microsatellite instability (MSI-H) have been shown to have increased overall survival and limited benefit from 5FU based chemotherapy. Additional research is necessary to clearly define the most appropriate way to use this marker and others in routine clinical practice.
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