Spread Through Air Spaces in Residual Tumor Classification for Clinical IA Lung Adenocarcinoma

BACKGROUND We aimed to validate the prognostic implication of uncertain resection [R(un)] proposed by International Association for the Study of Lung Cancer (IASLC) and evaluate the prognostic value of spread through air spaces (STAS) in reclassifying R classification among patients with lung adenocarcinoma following segmentectomy. METHODS We enrolled 1,007 patients who underwent segmentectomy for c-stage IA lung adenocarcinoma between 2014 and 2017. Recurrence-free survival (RFS) and overall survival (OS) were compared to evaluate the prognostic value of IASLC-R(un) and STAS. And whether STAS would skip into complementary lobectomy was evaluated in a prospective cohort. RESULTS Current IASLC-R(un) failed to significantly stratify the RFS (p=0.078) in segmentectomy and STAS was a stronger risk factor of poor prognosis (both RFS and OS: p<0.001). Moreover, the presence of STAS was associated with increased locoregional recurrence in patients undergoing segmentectomy (p<0.001) but not in those treated with lobectomy (p=0.187), indicating that only STAS-positive segmentectomy was consistent with the concept of R(un) in relapse pattern. After reclassifying STAS-positive segmentectomy into R(un) category, the proposed R(un) showed an improvement in prognosis stratification. In addition, 2 of 30 (6.2%) patients in the prospective cohort who underwent initial segmentectomy and complementary lobectomy had STAS clusters in the complementary lobectomy specimens. CONCLUSIONS Unfavorable prognosis, relapse patterns consistent with R(un), as well as pathological verification that saltatory spread of STAS observed in complementary lobectomy specimens supported reclassifying STAS-positive segmentectomy as R(un). And STAS is a critical concern for the surgical completeness evaluation following segmentectomy.