Ground glass opacity resection extent assessment trial (GREAT): A study protocol of multi-institutional, prospective, open-label, randomized phase III trial of minimally invasive segmentectomy versus lobectomy for ground glass opacity (GGO)-containing early-stage invasive lung adenocarcinoma

Abstract

BackgroundWith widely use of computed tomography (CT) screening, an increasing number of early-stage lung cancers appearing as ground glass opacity (GGO) have been detected. Therefore, attempts have been made to investigate the feasibility of segmentectomy instead of lobectomy for those patients with GGO. However, the two recently released phase III trials failed to distinguish between GGO-containing lesions from pure solid nodules in the inclusion criteria, and the surgical methods did not distinguish between minimally invasive surgery and open thoracotomy. In addition, total lesion size≤ 2cm was taken as the inclusion criterion, instead of the solid part size recommended in the eighth edition of Union for International Cancer Control/International Association for the Study of Lung Cancer/American Joint Committee on Cancer (UICC/IASLC/AJCC) staging system. Hence, this present trial aims to figure out whether minimally invasive segmentectomy shows superiority in perioperative outcomes and non-inferiority in oncological prognosis over minimally invasive lobectomy among patients with GGO-containing clinical stage T1a-T1b lung invasive adenocarcinoma (IADC).Methods/designSample sizes are 1024 patients, who will be randomized into minimally invasive segmentectomy and lobectomy groups . Patients will be collected from 19 hospitals in China. Patients with peripheral mixed ground glass opacity (mGGO) with 0.5cm<total lesion size ≤ 3cm and 0.5cm<solid component size ≤ 2cm in lung window on CT scan are enrolled. The primary endpoint is 5-year recurrence-free survival (RFS). The secondary endpoints are 5-year overall survival (OS), perioperative outcomes and pulmonary function preservation. Kaplan-Meier curves are plotted to compare the survival outcomes between the two arms. Subgroup analyses are also performed to investigate the benefit of segmentectomy among different clinical variables.DiscussionsIf the primary endpoint shows at least non-inferiority in 5-year RFS of segmentectomy to lobectomy, minimally invasive segmentectomy can be recommended as an alternative to minimally invasive lobectomy. If second endpoints show non-inferior 5-year OS along with better perioperative outcomes and/or better pulmonary function preservation of segmentectomy compared with lobectomy after the primary endpoint has reached, minimally invasive segmentectomy may become a preferred procedure for patients with GGO-containing clinical stage T1a-T1b IADCs.Trial registrationChinese Clinical Trial Registry. Trial registration number: ChiCTR2000037065.Clinical trial registrationhttps://www.chictr.org.cn/, identifier ChiCTR2000037065.