CALGB 140503 and the shift to sublobar resection for small, peripheral, node-negative NSCLC: historical context, secondary analyses, and next steps

The surgical management of early-stage non-small cell lung cancer (NSCLC) has been reshaped by contemporary randomized data supporting lung-sparing approaches in carefully selected patients. CALGB/Alliance 140503, a multicenter phase III trial, compared sublobar resection (wedge or segmentectomy) with lobectomy for peripheral, clinically node-negative NSCLC ≤2 cm, randomizing patients only after rigorous intraoperative nodal assessment. Sublobar resection proved noninferior to lobectomy with respect to disease-free survival, with comparable overall survival and recurrence patterns. Alongside other important randomized trials like JCOG 0802/WJOG 4607L, sublobar resection has now been established as an acceptable - and for some patients preferable - strategy for stage IA (≤ 2 cm) NSCLC. Beyond its primary results, CALGB 140503 has generated a series of secondary and exploratory analyses that continue to refine day-to-day clinical decision-making. This mini-review aims to synthesize the current state of insights from this trial, highlighting ongoing controversies and key gaps for future investigation that will further optimize the management of early-stage NSCLC.