STAS More than a Prognostic Marker—An Evolving Factor in Operative and Adjuvant Treatment Decisions in Early-Stage NSCLC

Since tumor spread through air spaces (STAS) was first described over a decade ago, numerous studies have demonstrated that it is a high-risk prognostic feature in non-small cell lung cancer (NSCLC). However, due to preoperative and intraoperative limitations in pathologic diagnosis, STAS is generally diagnosed following curative intent resection. While STAS should influence NSCLC treatment strategy-particularly upfront surgical decision-making-postoperative diagnosis of STAS has heretofore limited this possibility. While limited to retrospective studies, the current evidence suggests that patients with tumor STAS should undergo a more extensive anatomical resection-preferably a lobectomy, if they are candidates. These results are particularly important in the setting of the results of the JCOG0802 and CALGB 140503 randomized controlled trials which have begun a paradigm-shift toward sublobar resections for early-stage NSCLC, which may not hold similar benefit for early-stage STAS+ disease. The aims of this review are to: (1) detail the current evidence concerning choice of resection extent for STAS+ disease, (2) summarize the current evidence about optimum surgical margins for STAS+ disease, (3) detail the potential role for adjuvant chemotherapy in early-stage STAS+ disease, (4) assess the current limitations in preoperative STAS risk prediction and intraoperative STAS detection, and (5) highlight promising AI-based advancements which will allow surgeons to risk-stratify STAS probability or confirm STAS status intraoperatively. The main limitation of this review is the reliance on retrospective studies as there is a current lack of prospective or randomized data within STAS+ NSCLC, particularly regarding optimal resection strategy for STAS+ disease.