In September 2025, the IASLC Pathology Committee proposed a two-tier grading system for resected lung SqCC based on tumor budding.
Of these, 88.9% had low-grade tumors and 11.1% had high-grade tumors according to the IASLC tumor budding criteria.
Hong reported that patients with high-grade tumor budding were significantly more likely to have pathologic stage II or III cancers than those with low-grade tumor budding, at 75.4% versus 43.3%.
When the patients were stratified by tumor budding grade, there was also no benefit from adjuvant chemotherapy among low-grade patients.
Exploratory genomic profiling in a case-matched subset (n=100) showed that genetic alteration patterns differed by tumor budding grade.
A tumor budding-based grading system recently developed by the International Association for the Study of Lung Cancer (IASLC) could provide a more precise way to stratify risk in resected lung squamous cell carcinoma (SqCC) and help identify patients who may benefit from adjuvant chemotherapy, Korean research suggests.
“Our findings show that the newly proposed IASLC tumor budding-based grading system can identify patients with resected lung squamous cell carcinoma who have a poorer prognosis, while also suggesting that high-grade patients may be the group most likely to derive benefit from adjuvant chemotherapy,” said T.H. Hong, MD, PhD, of Yonsei University School of Medicine in Seoul, Republic of Korea. He presented the findings at the IASLC 2026 World Conference on Lung Cancer.
Hong explained to delegates that, despite being a major thoracic malignancy, lung SqCC has no standardized pathologic grading system, meaning that clinicians do not have a reproducible tool to stratify risk and guide adjuvant treatment. Traditional keratinization-based grading has limited and inconsistent prognostic utility among these patients, Hong said.
In September 2025, the IASLC Pathology Committee proposed a two-tier grading system for resected lung SqCC based on tumor budding.
Although the system was validated across more than 1500 cases from multiple institutions, with high-grade tumors defined as 10 or more buds per 0.785 mm2, the findings were not externally validated in a real-world setting, did not assess predictive value for clinical benefit of adjuvant therapy, and did not include genomic characterization.
To address this, Hong and team retrospectively reviewed data for 585 consecutive patients with lung SqCC who underwent upfront resection with curative intent at a single center in Korea between 2015 and 2022. Of these, 88.9% had low-grade tumors and 11.1% had high-grade tumors according to the IASLC tumor budding criteria.
Hong reported that patients with high-grade tumor budding were significantly more likely to have pathologic stage II or III cancers than those with low-grade tumor budding, at 75.4% versus 43.3%.
Patients with high-grade tumors also had a significant 1.84-fold increased risk for death and a 1.88-fold increased risk for disease recurrence or death than those with low grade tumors, after adjustment for potential confounders.
In a subgroup analysis among 371 patients with pathologic stage IB–III disease who were eligible for adjuvant treatment, the researchers found that there was no overall disease-free survival (DFS) benefit from adjuvant chemotherapy.
When the patients were stratified by tumor budding grade, there was also no benefit from adjuvant chemotherapy among low-grade patients.
There was, however, a clinically meaningful trend toward DFS benefit from adjuvant chemotherapy among high-grade patients, at a non-significant hazard ratio of 0.52.
This suggests that “grade may help identify who benefits from adjuvant therapy,” said Hong.
Exploratory genomic profiling in a case-matched subset (n=100) showed that genetic alteration patterns differed by tumor budding grade. For example, PI3K3CA missense mutations only occurred among patients with low grade tumors whereas disruptive TP53 mutations increased across budding categories and were more common in high-grade tumors.
“This exploratory analysis suggests that that distinct biological programing may underlie this new grading system,” Hong remarked.
He concluded that the findings “extend the clinical and biological relevance of the newly proposed grading system,” noting that prospective multicenter validation is now warranted.
