Spread through air spaces predicted relapse after both lobectomy and segmentectomy in JCOG0802 stage IA NSCLC

A segmentectomy trial that left the place of STAS open

JCOG0802/WJOG4607L randomised patients with small peripheral NSCLC to segmentectomy or lobectomy. STAS and histologic tumour grade had both been reported as adverse prognostic factors in NSCLC before this analysis.

What had not been settled, according to the authors, was how either factor bears on the extent of resection. The trial population gave them a way to test that question in patients who had been randomised between the two operations and followed under a common protocol.

STAS in 38% of tumours, with roughly twice the hazard of relapse

Across all 593 tumours, the presence of STAS gave a hazard ratio of 2.204 for relapse-free survival and 1.917 for overall survival, each with p<0.001.

On multivariable analysis STAS remained an independent adverse factor for relapse-free survival (p<0.001) and for overall survival (p=0.009). STAS was scored by 32 expert pulmonary pathologists from around the world, a feature that can be difficult to score consistently.

Higher local recurrence with STAS after either operation

The association between STAS and local recurrence reached p=0.012 in the 294 tumours removed by lobectomy and p=0.002 in the 299 removed by segmentectomy.

STAS also predicted shorter relapse-free survival independently within each surgical subgroup. For overall survival the picture differed by procedure: STAS was an independent predictor in the lobectomy subgroup and did not reach that threshold in the segmentectomy subgroup. The subgroups are each about half the size of the full cohort, and the abstract does not offer an explanation for the difference.

Grade 3 adenocarcinoma travelled with STAS and predicted survival on its own

Among invasive non-mucinous adenocarcinomas, grade 3 histology showed a strong association with STAS (p<0.001), and grade 3 tumours had poor outcomes.

Both STAS and grade 3 independently predicted shorter relapse-free survival, whereas only grade 3 independently predicted overall survival. The two features are closely associated, and within adenocarcinomas the overall survival signal appeared to track with grade more than with STAS.

Both factors proposed for risk stratification in pT1a/bN0 disease

The authors conclude that the results reinforce STAS and high-grade adenocarcinoma as clinically significant prognostic factors, and that they support incorporating both into risk stratification for patients with pT1a/bN0 NSCLC.

In this analysis STAS was scored by pathologists on tumours that had already been resected. For STAS to guide the choice between segmentectomy and lobectomy, it would need to be identified before or during the operation, and the abstract does not address how reliably that can be done.