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.