Dr Grant on the Unanswered Questions in Perioperative NSCLC

When you look at a lot of our symposiums over the course of this entire weekend, a lot of our oral presentations focus on our ctDNA, and I think what we see is, in prime time right now, we are not ready.

Chris Grant, MD, a hematology-oncology fellow at the University of California, San Diego, discussed unresolved questions in the perioperative management of non–small cell lung cancer (NSCLC), including neoadjuvant versus perioperative sequencing, selection for adjuvant immunotherapy, and the readiness of circulating tumor DNA (ctDNA).

At the 2026 IASLC World Conference on Lung Cancer (WCLC), Grant noted that ctDNA featured across multiple oral sessions. The current standard for assessing response remains CT-guided imaging, with event-free survival, disease-free survival, and overall survival as the downstream measures. Before liquid assays can be incorporated, he said, tumor-informed platforms need to demonstrate adequate sensitivity and specificity for detecting recurrence relative to imaging — and studies must evaluate ctDNA both alongside and independent of diagnostic CT. He characterized the field as closer than in prior years but not yet there.

Whether patients should receive neoadjuvant therapy alone or a full perioperative course remains unsettled, Grant said. He pointed to cooperative group trials as the mechanism needed to compare the 2 strategies directly. Regimens also differ in duration: the phase 3 CheckMate 816 trial (NCT02998528) used 3 cycles of chemoimmunotherapy, while other perioperative regimens use 4.

In practice, he said, the decision often turns on patient priorities and on resectability — if a surgeon deems a tumor unresectable, a longer neoadjuvant course may be favored, though he noted that approach lacks supporting data.

A related question is whether patients achieving a pathologic complete response (pCR) need adjuvant immunotherapy at all. In the CheckMate 816 subgroup analysis, 24% of patients achieved a pCR, and Grant said survival benefit was present among those who went on to receive adjuvant immunotherapy. On that basis, he said the field is likely over-treating some of these patients, and that the case is harder to assess in those with a major pathologic response.

Better stratification, in his view, would draw on disease stage, nodal status — particularly bulky N2 disease, which he acknowledged is difficult to define consistently — and passenger mutations. He also raised trial design directly, asking where randomization should occur: whether patients should be randomized at the time of surgery to receive adjuvant therapy or not, using pCR or companion biomarkers to guide the assignment.

In a separate segment at WCLC 2026, Grant discussed how early-career oncologists can navigate large disease-specific meetings, identify mentors, and develop research questions during fellowship.