pMMR局部晚期结肠癌新辅助治疗的研究进展

Advances in Neoadjuvant Chemotherapy for Locally Advanced Colon Cancer with pMMR

摘要: 新辅助化疗对于熟练错配修复(pMMR)局部晚期结肠癌(LACC)患者是安全的。FOxTROT试验表明，cT3-4 LACC患者接受新辅助化疗2年后，残余癌症和复发癌症有所减少。对于错配修复缺陷(dMMR) LACC患者，如果可能的话，应避免术前化疗，因为超过50%的dMMR癌症没有病理反应。早期对MMR状态进行普遍检测对于选择合适的新辅助治疗至关重要。对LACC CT分期的担忧限制了新辅助化疗的采用，因为CT上大约25%的cT3-T4癌症患者患有低风险II期疾病。恶性淋巴结CT标准的制定应可降低过度分期的风险。需要采用多学科方法来确定接受新辅助治疗的患者。值得注意的是，新辅助免疫疗法被发现可在pMMR LACC患者的亚群中引起主要病理反应，表明有可能治愈更多患有这种常见癌症的患者。cT4 LACC患者，无论是II期还是III期，尽管接受氟嘧啶加奥沙利铂辅助化疗，仍有很大的复发风险。我们建议对所有cT4b LACC (dMMR和pMMR)患者进行新辅助全身治疗。T4b疾病的特征通常由放射学报告。因为依从性高，残留和复发的改善，我们建议对cT4b pMMR LACC患者使用三个周期的FOLFOX化疗。目前，多项关于pMMR LACC的新辅助化疗、免疫治疗及靶向治疗研究，以及dMMR LACC的免疫治疗试验正在进行中，预计将取得显著成果。

Abstract: Neoadjuvant chemotherapy is safe for patients with locally advanced colon cancer (LACC) with pMMR. The FOxTROT trial demonstrated that cT3-4 LACC patients who received neoadjuvant chemotherapy showed a reduction in residual cancer and recurrent cancer after 2 years. For patients with dMMR LACC, preoperative chemotherapy should be avoided if possible, as more than 50% of dMMR cancers have no pathological response. Early universal detection of MMR status is essential for the selection of appropriate neoadjuvant therapy. Concerns about CT staging of LACC have limited the adoption of neoadjuvant chemotherapy, as approximately 25% of cT3-T4 cancer patients on CT have low-risk stage II disease. The development of CT criteria for malignant lymph nodes should reduce the risk of excessive staging. A multidisciplinary approach is needed to identify patients receiving neoadjuvant therapy. Notably, neoadjuvant immunotherapy was found to cause major pathological responses in a subpopulation of pMMR LACC patients, suggesting the potential to cure more patients with this common cancer. Patients with cT4 LACC, whether stage II or III, are at significant risk of recurrence despite receiving fluoropyrimidine plus oxaliplatin adjuvant chemotherapy. We recommend neoadjuvant systemic therapy for all cT4b LACC (dMMR and pMMR) patients. The characteristics of T4b disease are usually reported by radiology. Because of the high adherence and improvement in residual and recurrent disease, we recommend three cycles of FOLFOX chemotherapy for cT4b pMMR LACC patients. At present, a number of neoadjuvant chemotherapy, immunotherapy and targeted therapy studies on pMMR LACC, as well as immunotherapy trials on dMMR LACC are under way and are expected to achieve significant results.