Transforming resectable NSCLC care with neoadjuvant/ perioperative IO

Immunotherapy (IO) has shifted the management of resectable non-small-cell lung cancer (NSCLC) towards a multimodality approach that deepens treatment response, resulting in meaningful gains in event‑free survival (EFS) and overall survival (OS). At an industry-sponsored symposium during the 33^rd Annual Scientific Meeting of the Hong Kong College of Radiologists, experts discussed the evidence supporting standard-of-care (SoC) neoadjuvant and perioperative IO in patients with resectable NSCLC, as well as the crucial role of multidisciplinary teams (MDTs) in optimizing treatment outcomes in this population.

Neoadjuvant IO in resectable NSCLC: Improving patient selection
Neoadjuvant IO plus chemother­apy has emerged as SoC for eligi­ble patients with resectable NSCLC. [NCCN Clinical Practice Guidelines in Oncology, Non-Small Cell Lung Can­cer, version 3.2026]

“In a departure from the previ­ous ‘surgery only’ approach, many surgeons now recognize the impor­tance of multimodality treatment of locally advanced NSCLC,” said Dr Teddy Wong of the Division of Car­diothoracic Surgery, Tuen Mun Hos­pital, Hong Kong. [Ann Thorac Surg 2025;119:16-33]

“We are aware that approximately 20 percent of patients may not pro­ceed with surgery after neoadjuvant chemoimmunotherapy,” he noted. [Curr Oncol 2025;32:110] “However, we’ve learnt that a key consideration to ensure lower attrition rates is to improve patient selection.”

“At our institution, we previously offered neoadjuvant chemoimmuno­therapy to patients with borderline re­sectable tumours,” continued Wong. “This resulted in a high attrition rate, with >60 percent of cases unable to proceed with surgery. Nowadays, we include more cases with bulky lymph nodes but readily resectable tumours. This careful selection almost halved our surgery attrition rate in a single year to about 30 percent.” (Table)

“Similarly, the Society of Thoracic Surgeons expert consensus recom­mendations underscore the impor­tance of upfront assessment of sur­gical resectability,” stressed Wong.

“This ensures that patients deemed to have unresectable disease at the outset are not given neoadjuvant therapy in an attempt to convert their disease to a resectable case.” [Ann Thorac Surg 2025;119:16-33]

“Prospective data from the phase III MDT‑BRIDGE trial reinforce this paradigm shift,” added Dr Molly Li of the Department of Clinical Oncology, Chinese University of Hong Kong. “When patients with EGFR/ALK‑negative, clearly resectable stage IIB–IIIB disease received MDT‑guid­ed neoadjuvant IO plus chemother­apy, 93 percent proceeded to sur­gery, implying an attrition rate of only about 7 percent.” [Clin Lung Cancer 2024;25:587-593.e3; Reck M, et al, ESMO 2025, abstract LBA65]

Optimizing neoadjuvant and perioperative IO strategies in resectable NSCLC
“In patients with resectable NSCLC, about half will have disease recurrence after surgery, with adju­vant chemotherapy improving surviv­al by only 5 percent,” noted Li. [Clin Lung Cancer 2024;25:587-593.e3; J Clin Oncol 2008;26:3552-3559]

Neoadjuvant and perioperative IO-based regimens are now pre­ferred for locally advanced resect­able NSCLC. “The three phase III trials studying adjuvant IO produced very conflicting results. In contrast, CheckMate 816, the only neoad­juvant study, showed a statistically significant absolute gain of approxi­mately 10 percent in OS,” explained Li. (Figure) [NCCN Clinical Practice Guidelines in Oncology, Non-Small Cell Lung Cancer, version 2.2026; Lancet 2021;398:1344-1357; Lancet Oncol 2022;23:1274-1286; Goss G, et al, ESMO 2024, abstract LBA48; N Engl J Med 2022;386:1973-1985; N Engl J Med 2025;393:741-752]

CheckMate 816: Neoadjuvant nivolumab improves OS
The open-label CheckMate 816 trial was the first positive phase III study of a neoadjuvant IO-based combination for patients with re­sectable NSCLC. [N Engl J Med 2022;386:1973-1985; Breathe (Sheff) 2024;20:240044]

Significantly more patients who received neoadjuvant nivolumab plus platinum-based chemothera­py achieved pathological complete response (pCR) than those who re­ceived chemotherapy alone (odds ratio, 13.94; 99 percent confidence interval [CI], 3.49–55.75; p<0.001). EFS was also significantly longer in the nivolumab group (hazard ratio [HR], 0.63; 97.38 percent CI, 0.43–0.91; p=0.005). [N Engl J Med 2022;386:1973-1985]

Importantly, long-term follow-up showed a statistically significant benefit with 5‑year OS rates of 65.4 vs 55.0 percent with nivolumab plus chemotherapy vs chemother­apy alone (HR, 0.72; 95 percent CI, 0.523–0.998; p=0.048). (Figure) [N Engl J Med 2025;393:741-752]

“These results also highlight pCR as an important prognostic marker in resectable NSCLC,” pointed out Li. “In the nivolumab group, among patients with pCR, there were no lung cancer–related deaths and the 5‑year OS rate was almost 100 percent [95.3 percent] vs 55.7 per­cent in patients without pCR [HR, 0.11; 95 percent CI, 0.04–0.36]. This suggests that pCR is a near‑surrogate for cure in this setting.” [N Engl J Med 2025;393:741-752; Nat Med 2024;30:218-228]

Checkmate 77T: Perioperative nivolumab improves EFS
“Consistent benefit has also been demonstrated across periop­erative IO-chemotherapy studies,” said Li. [Cascone T, et al, ASCO 2025, abstract LBA8010; N Engl J Med 2023;389:491-503; JAMA 2024;331:201-211; N Engl J Med 2023;389:1672-1684]

The phase III CheckMate 77T trial demonstrated statistically sig­nificant and clinically meaningful im­provements in EFS with periopera­tive nivolumab in patients with stage IIA–IIIB resectable NSCLC. Patients received up to four cycles of neo­adjuvant nivolumab or placebo plus chemotherapy (Q3W), followed by adjuvant nivolumab or placebo for up to 13 cycles (Q4W). Updated results showed that subsequently adding adjuvant nivolumab to this neoadju­vant regimen further improved EFS vs placebo (HR, 0.61; 95 percent CI, 0.46–0.80; 30-month EFS rates, 61 percent vs 43 percent) in all patients, regardless of disease stage, tumour histology, or PD-L1 expression. Lung cancer–specific OS data also demonstrated a favourable trend de­spite data immaturity. [N Engl J Med 2024;390:1756-1769; Cascone T, et al, ASCO 2025, abstract LBA8010]

Individualizing IO strategies by pCR with nivolumab
“Given its profound prognostic im­plications in patients with resectable NSCLC, pCR may become a practi­cal anchor for tailoring IO regimens,” commented Li. “Cross‑trial observa­tions indicate that in CheckMate 816, where adjuvant nivolumab was not mandated, outcomes for patients with pCR were outstanding even without routine postoperative IO, whereas in perioperative trials, patients without pCR appear to derive additional EFS benefit from adjuvant IO.” [N Engl J Med 2025;393:741-752; N Engl J Med 2024;390:1756-1769; N Engl J Med 2023;389:491-503; N Engl J Med 2023;389:1672-1684]

“A patient‑level propensity‑weighted comparison of CheckMate 816 and 77T supports this observa­tion. Survival curves for patients with pCR are similar regardless of periop­erative or neoadjuvant‑only IO, but perioperative nivolumab seems to improve EFS, including in patients without pCR,” shared Li. [Forde PM, et al, WCLC 2024, abstract PL02.08] “Personally, I would favour flexible regimens that permit de‑escalation, potentially omitting or abbreviating adjuvant IO in patients with pCR, while maintaining the option to con­tinue adjuvant nivolumab in those with residual disease.”

MDT-driven perioperative IO in resectable NSCLC
With neoadjuvant and periopera­tive IO recognized as SoC for patients with resectable NSCLC, a multidisci­plinary management approach has become crucial. International recom­mendations specifically suggest that treatment should be individualized and ideally guided by an MDT in a tumour board setting with surgeons, medical oncologists, pathologists, pulmonologists, radiologists and supportive care staff. [J Thorac Oncol 2024;19:1373-1414]

Summary
Neoadjuvant and periopera­tive IO-based therapies, including nivolumab-containing regimens, are supported by data from CheckMate 816 and 77T trials and improve pCR, EFS and long-term OS in patients with resectable NSCLC. pCR may be used to guide adjuvant IO needs. Ef­fective MDT coordination and stream­lined pathways remain essential for minimizing surgery attrition rates and effectively implementing neoad­juvant and perioperative IO-based strategies.