IASLC Tumor Budding Grade Identifies High-Risk Lung Squamous Cell Carcinoma Patients

IASLC Tumor Budding Criteria for Resected Lung SqCC

Lung squamous cell carcinoma lacks a standardized pathologic grading system, leaving clinicians without a reproducible tool to stratify risk and guide adjuvant treatment. Traditional keratinization-based grading offers limited prognostic utility, according to T.H. Hong of Yonsei University School of Medicine in Seoul, Republic of Korea. To fix this gap, the IASLC Pathology Committee proposed a two-tier grading system in September 2025 that classifies resected lung SqCC as low grade or high grade solely based on tumor budding.

While the system was initially validated across more than 1,500 cases from multiple institutions—defining high-grade tumors as 10 or more buds per 0.785 mm2—it lacked real-world external validation and genomic characterization. Hong and his research team sought to evaluate these metrics by retrospectively reviewing 585 consecutive patients who underwent curative-intent upfront resection at Yonsei University Medical Center between 2015 and 2022.

Validation Findings and Survival Risks in Korean Cohort

Among the 585 patients in the Yonsei University cohort, 520 patients, or 88.9%, had low-grade tumors, while 65 patients, or 11.1%, had high-grade tumors, according to data presented at the conference. High-grade tumor budding strongly correlated with advanced disease stages. Patients with high-grade tumors were significantly more likely to present with pathologic stage II or III cancers compared to those with low-grade tumor budding, at 75.4% versus 43.3%.

Adjuvant Chemotherapy Impact on High-Grade and Low-Grade Subgroups

Evaluating treatment response required looking closely at specific clinical subgroups. In a subgroup analysis of 371 patients with pathologic stage IB–III disease eligible for adjuvant treatment, researchers found no overall disease-free survival benefit from adjuvant chemotherapy across the entire group, according to study findings reported by Mirage News. Stratifying these patients by tumor budding grade revealed a clearer split.

Low-grade patients showed no disease-free survival benefit from adjuvant chemotherapy. Conversely, high-grade patients demonstrated a clinically meaningful trend toward disease-free survival benefit from adjuvant treatment, showing a non-significant hazard ratio of 0.52. This indicates that the grading system helps flag the specific patient subset most likely to derive clinical benefit from adjuvant therapy.

Genomic Profiling Reveals Divergent Oncogenic Programs

Exploratory genomic profiling in a case-matched subset of 100 patients demonstrated that distinct biological programming underlies the IASLC tumor budding-based grading system. While global genomic instability showed no difference between grades, genetic alteration patterns shifted noticeably. PI3K pathway alterations, including PI3K3CA missense mutations, occurred exclusively in low-grade tumors. Meanwhile, disruptive and truncating TP53 mutations increased across budding categories and appeared more commonly in high-grade tumors.

These biological differences extend the clinical and biological relevance of the grading framework. Hong noted that prospective multicenter validation remains necessary to confirm its ultimate role in treatment selection.

Frequently Asked Questions

What is the IASLC tumor budding-based grading system for lung cancer?

It is a two-tier grading system proposed by the IASLC Pathology Committee that classifies resected lung squamous cell carcinoma as low-grade or high-grade based on tumor budding counts of 10 or more buds per 0.785 mm2.

How does tumor budding grade affect prognosis?

According to research presented by T.H. Hong, high-grade tumor budding is independently associated with worse overall and disease-free survival, carrying nearly double the risk of death or disease recurrence compared to low-grade tumors.

Can tumor budding grade predict adjuvant chemotherapy benefits?

Yes. Subgroup analyses show that high-grade patients demonstrate a clinically meaningful trend toward disease-free survival benefit from adjuvant chemotherapy, whereas low-grade patients derive no observed benefit.