Day Two: ISOPT Annual Meeting

Van Schil frames the surgeon's job as complete R0 resection, judged on technical resectability, oncological resectability, and the patient's functional operability, always inside a multidisciplinary team. He walks the ESMO-based pathways for stage 1 through 3, then turns to the unsettled definition of resectability itself, where the new EORTC consensus is meant to guide discussion rather than close it.

Key points for clinicians:

• Complete R0 resection is the aim. IASLC criteria from 2005 call for at least six nodal stations removed, three from the mediastinum including subcarinal station 7. Falling short is an uncertain resection and is associated with roughly 20 fewer months of overall survival when nodes are positive.

• Stage 1, medically operable: surgery is preferred. Sublobar resection can be discussed for node-negative tumors under 2 cm, otherwise lobectomy. Larger tumors with EGFR ex19del or L858R receive osimertinib for three years.

• Medically inoperable stage 1 usually starts with SBRT followed by surveillance, with salvage surgery considered on local progression.

• Stage 2 and 3 decisions hinge on EGFR and PD-L1 testing, sorting patients across adjuvant chemotherapy, checkpoint inhibitors, and targeted therapy, with surgery up front for EGFR-mutant or ALK-rearranged resectable disease.

• Resectability is still not harmonized. The EORTC consensus definition of stage 3 NSCLC (Dingemans, Lancet Respiratory Medicine, 2026) is explicitly work in progress. Trials like PACIFIC never gave a precise definition of unresectable disease, and neoadjuvant and perioperative trials often left resectable undefined.

• Anatomy sets limits: T4 by separate nodules or size is generally resectable, while invasion of the myocardium, trachea above the carina, esophagus, or spinal cord is usually unresectable.

Lung cancer has become the working model for precision oncology, and the number of actionable targets in early-stage disease is growing faster than the trials to test them. Professor Fred Hirsch walks through that acceleration and lands on the harder question underneath it: with immunotherapy, only about 40 percent of lung cancer patients see significant benefit, and we still do not select the right ones well.

Hirsch traces the move of targeted therapy and immunotherapy from advanced disease into the adjuvant, neoadjuvant, and perioperative settings, then Professor Oscar Arrieta adds a note of restraint on when a randomized trial is truly required. The through-line is a field advancing quickly on drugs while the questions that matter to patients, cure and treatment duration, are still open.

Key points for clinicians:

• In early-stage EGFR-positive disease, adjuvant osimertinib (ADAURA) showed a clear disease-free survival benefit and, so far, an overall survival benefit. Adjuvant alectinib (ALINA) is now standard of care for ALK-positive patients.

• Fourth-generation EGFR TKIs are being designed for better CNS penetration than third-generation osimertinib, with early data presented at ASCO this year. In unresectable stage 3 EGFR disease, the LAURA study favored osimertinib.

• The proliferation of rare targets, some at 1 to 2 percent of patients, raises a real design question: is a randomized trial needed for every actionable mutation before moving it into early-stage disease?

• With immunotherapy, roughly 40 percent of patients benefit meaningfully. PD-L1 remains the working selector: above 50 percent, IO monotherapy; below 50 percent, chemo plus IO; below 1 percent, chemo plus IO or chemo plus dual IO.

• Neoadjuvant or perioperative immunotherapy carries benefit even in PD-L1 negative tumors, about 20 percent of patients, though the PD-L1 negative space is still unsettled.

• After neoadjuvant therapy, about 20 percent of US patients reach a complete pathologic response, higher in Asia. The SWOG-initiated INSIDE trial tests adjuvant IO versus surveillance in those patients, with a separate ETOP trial for non-pCR.

• Arrieta's caution: not all actionable mutations carry the same magnitude of benefit, and some may not change survival if the same therapy can be given at recurrence.