Neoadjuvant chemotherapy with gemcitabine plus cisplatin followed by radical liver resection versus radical liver resection alone in incidentally detected gallbladder carcinoma after simple cholecystectomy – A phase III study utilizing the German Registry

胆囊癌是第五大常见的消化道肿瘤，总的5年生存率不到5%。由于腹腔镜胆囊切除术(LC)的高频率，更多的偶发发现被诊断为胆囊癌。三分之二的胆囊癌被称为偶发胆囊癌(IGBC)。德国的IGBC病例登记在德国偶发胆囊癌登记处(GR)，由当前试验的PI监督。分期调整治疗包括第二次肝脏根治术和LC后的淋巴清扫(IRR-立即根治性再次切除)。根据德国的S3指南，建议在T2期和更晚期的T期患者中使用该方法。IGBC的治疗管理中存在两个主要问题。首先，胆囊癌的外科治疗仍然不充分[1-3]。GR中只有49%的T2-T3癌达到了推荐的IRR。在这项拟议的研究中，作为研究设计的强制性部分，所有试验患者都将获得IRR。第二，即使在根治性手术后，pt2-3癌症--显著代表了大多数肿瘤--的结果仍然很差[3]。根据GR，T2的5年OS在有IRR的情况下是38%，没有IRR的是22%[7，11]。在T3中，有IRR的是18%，没有IRR的是12%[7，11]。通过纯粹的手术概念来治愈这类患者似乎是不可能的。多模式概念在食管胃、直肠和其他恶性肿瘤中的令人鼓舞的结果为在IGBC治疗的早期阶段使用这种治疗提供了额外的理论基础。试验中的患者将随机接受IRR+/-围手术期化疗。主端点是操作系统。

Gallbladder carcinoma is the fifth most common neoplasm of the digestive tract, with an overall 5-year survival less than 5%. Due to the high frequency of laparoscopic cholecystectomies (LC), more incidental findings of gallbladder carcinomas are diagnosed. 2/3 of gallbladder carcinomas are so called incidental gallbladder carcinomas (IGBC). Cases IGBC in Germany are registered in theGerman Registry of Incidental Gallbladder Carcinoma (GR) overseen by the PI of the current trial. Stage-adjusted therapy includes second radical surgery of the liver and lymphadenectomy after LC (IRR -immediate radical re-resection). According to the S3 Guidelines in Germany this is recommended in cases of T2 and more advanced T-stages.There are two main problems in the curative management of IGBC. First of all, surgical management of gallbladder cancer remains inadequate [1-3]. Only 49% of T2-T3 carcinomas in the GR underwent the recommended IRR. In the study proposed, all trial patients will receive the IRR as mandatory part of the study design.Secondly, even after radical surgery, the outcome pT2-3 carcinomas – which notably represent the majority of the tumors, remains poor [3]. According to the GR, the 5-year OS of T2 is 38% with and 22% without IRR [7, 11]. In T3 it is 18% with and 12% without IRR [7, 11]. Cure of such patients by a pure surgical concept does not seem to be achievable. The encouraging results of multimodal concepts in esophagogastric-, rectal-, and other malignancies provide an additional rationale to use this kind of treatment in the early phase of IGBC management. Patients in the trial will be randomized to IRR +/- perioperative chemotherapy. Primary endpoint is OS.