Zhu Zhenggang
Department of Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai Institute of Digestive Surgery, Shanghai Key Laboratory of Gastric Neoplasm, Shanghai 200025, China Email:
Zhonghua Wei Chang Wai Ke Za Zhi. 2018 Oct 25;21(10):1087-1092.
Gastric cancer is the second most common malignancy and the one of the leading causes of cancer-related death in China. In particular, the survival rate of patients with stage IV or unresectable gastric cancer is very poor. Conversion therapy for stage IV gastric cancer has been the main subject with much attention recently. It is defined to achieve an R0 surgical resection after chemotherapy for originally unresectable cancer due to technical and/or oncological reasons. However, the optimal indications for conversion surgery are still controversial, and how to select the most appropriate candidates for conversion therapy remains to be clarified. A new biological category for stage IV gastric cancer proposed by K Yoshida from Gifu University has been tested out in some trials, from which stage IV gastric cancer can be divided into two different classifications based on the absence (category 1: potentially resectable metastasis and category 2: marginally resectable metastasis) or presence (category 3:incurable and unresectable metastasis and category 4: non-curable metastasis) of macroscopic peritoneal dissemination. The optimal indications for conversion therapy mainly include the patients with category 2, and partially for patients with categories 3 and 4. A surgery-oriented classification proposed by Peking University Cancer Hospital tried to classify the stage IV gastric cancer for conversion therapy. It would be classified as resectable and unresectable categories, depending on uhether R0 resection is available by preoperative evaluation. In this classification, unresectable cancer can be further classified as conversed, partly conversed and non-conversed types based on extent of cancer metastasis. The resection of primary and metastatic lesion in unscreened stage IV gastric cancer was not testified to improve survival. REGATTA trial has identified no significant difference in survival rate between the chemotherapy only and palliative gastrectomy with postoperative chemotherapy for stage IV gastric cancer with a single non-curable factor. With development of conversion therapy, a consensus has been reached that the patients with unresectable gastric cancer initially exhibiting one non-curative factor, if having clinical response to chemotherapy, may obtain a survival benefit from subsequent R0 radical gastrectomy. Several novel combined chemotherapy regimens occasionally allow for conversion of an initially unresectable gastric cancer to resectable cancer in clinical practice. Conversion surgery may result in long-term survival in selected patients who respond to chemotherapy. Several previous studies have evaluated the positive prognostic role of surgery after chemotherapy in stage IV gastric cancer patients with one non-curative factor, such as peritoneal metastasis, para-aortic lymph node metastasis or liver metastasis. Gastric cancer is a highly heterogeneous tumor in nature, consisting of varying aggressive biological characteristics. Oncologically stage IV gastric cancer is a systemic disease, and the complete response to any therapy is really very rare, so that conversion therapy is a great clinical challenging problem for gastric cancer patients. Due to the multi-pathway metastasis, perioperative systemic chemotherapy is the most important in conversion therapy for stage IV gastric cancer, and a radical surgical resection is the key to improve prognosis. A good local control does not necessarily lead to prolonged survival in patients with stage IV gastric cancer, in which other sites metastases often emerge even after successful local-regional cancer-oriented treatment. To date, most reports of conversion therapy for gastric cancer were from single-center or retrospective study. If more reliable evidences are to be obtained, more multi-center and prospective RCT studies must be carried out.
胃癌是中国第二大常见恶性肿瘤,也是癌症相关死亡的主要原因之一。特别是,IV期或不可切除胃癌患者的生存率非常低。IV期胃癌的转化治疗是近年来备受关注的主要课题。它被定义为由于技术和/或肿瘤学原因,对原本不可切除的癌症进行化疗后实现R0手术切除。然而,转化手术的最佳适应证仍存在争议,如何选择最合适的转化治疗候选者仍有待明确。岐阜大学的K Yoshida提出的IV期胃癌新生物学分类已在一些试验中得到验证,根据宏观腹膜播散的有无(分类1:潜在可切除转移和分类2:边缘可切除转移)或存在(分类3:不可治愈和不可切除转移以及分类4:不可治愈转移),IV期胃癌可分为两种不同的分类。转化治疗的最佳适应证主要包括分类2的患者,部分包括分类3和4的患者。北京大学肿瘤医院提出的以手术为导向的分类试图对IV期胃癌进行转化治疗分类。根据术前评估是否可进行R0切除,可分为可切除和不可切除两类。在这种分类中,不可切除的癌症可根据癌症转移程度进一步分为转化型、部分转化型和未转化型。未经筛选的IV期胃癌切除原发灶和转移灶并未证实能提高生存率。REGATTA试验发现,对于仅有一个不可治愈因素的IV期胃癌,单纯化疗与姑息性胃切除术后化疗的生存率无显著差异。随着转化治疗的发展,已达成共识,即最初表现为一个非治愈因素的不可切除胃癌患者,如果对化疗有临床反应,可能从随后的R0根治性胃切除术中获得生存益处。在临床实践中,几种新型联合化疗方案偶尔可使最初不可切除的胃癌转化为可切除癌症。转化手术可能使对化疗有反应的选定患者获得长期生存。先前的几项研究评估了化疗后手术对有一个非治愈因素(如腹膜转移、主动脉旁淋巴结转移或肝转移)的IV期胃癌患者的积极预后作用。胃癌本质上是一种高度异质性肿瘤,具有不同的侵袭性生物学特征。肿瘤学上的IV期胃癌是一种全身性疾病,对任何治疗的完全缓解都非常罕见,因此转化治疗对胃癌患者来说是一个巨大的临床挑战问题。由于多途径转移,围手术期全身化疗在IV期胃癌转化治疗中最为重要,根治性手术切除是改善预后的关键。良好的局部控制不一定能延长IV期胃癌患者的生存期,即使在成功进行以局部区域癌症为导向的治疗后,其他部位仍常出现转移。迄今为止,大多数胃癌转化治疗的报告来自单中心或回顾性研究。如果要获得更可靠的证据,必须进行更多的多中心和前瞻性随机对照试验研究。