Introduction:
Spread through air spaces (STAS) is a form of invasion wherein tumor cells extend beyond the tumor edge within the lung parenchyma. In lung adenocarcinoma (ADC), we investigated the (a) association between STAS and procedure-specific outcomes (sublobar resection and lobectomy), (b) effect of surgical margin/tumor diameter ratio in STAS-positive patients, and (c) potential utility of frozen section (FS) for detecting STAS intraoperatively.
Methods:
We investigated 1497 patients who underwent lobectomy (n=970) or sublobar resection (n=527) for T1N0M0 lung ADC, following propensity-score matching. Outcomes were analyzed using a competing-risks approach. The effect of margin/tumor ratio on recurrence pattern (locoregional and distant) was investigated in sublobar patients. Five pathologists evaluated the feasibility of intraoperatively identifying STAS using FS (sensitivity, specificity, interrater reliability).
Results:
On multivariable analysis following propensity-score matching (349 pairs/procedure), sublobar resection was significantly associated with recurrence (subhazard ratio, 2.84; P<0.001) and lung cancer-specific death (subhazard ratio, 2.63; P=0.021) in patients with STAS but not in those without STAS. Patients with STAS who underwent sublobar resection had a higher risk of locoregional recurrence regardless of margin/tumor ratio (margin/tumor ratio ≥1 vs. <1: 5-year cumulative incidence of recurrence [CIR], 16% and 25%); among patients without STAS, locoregional recurrences occurred in patients with margin/tumor ratio <1 (5-year CIR, 7%). Sensitivity and specificity for detecting STAS by FS were 71% and 92%, with substantial interrater reliability (Gwet's AC1, 0.67).
Conclusions:
In T1 lung ADC patients with STAS, lobectomy was associated with better outcomes than sublobar resection. Pathologists can recognize STAS on FS.