Tumor Budding Grading May Predict Chemotherapy Benefit in Resected Lung Squamous Cancer

Outcomes after resection for lung squamous cell carcinoma (SqCC) vary substantially, and the uneven benefit of adjuvant chemotherapy complicates postsurgical treatment decisions. Pathologic markers that refine risk assessment could help clinicians identify patients most likely to benefit from additional therapy. Supporting this approach, new findings show that the International Association for the Study of Lung Cancer (IASLC) two-tier grading system, based on tumor budding, identifies higher-risk patients and may help guide adjuvant treatment selection.

Investigators evaluated the 2025 IASLC two-tier grading system, which classifies resected lung SqCC as low or high grade based solely on tumor budding, to assess its ability to stratify prognosis and inform adjuvant therapy selection. The findings were presented at the IASLC 2026 World Conference on Lung Cancer (WCLC).

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Investigators retrospectively reviewed 585 consecutive patients who underwent curative-intent upfront resection at Yonsei University Medical Center from 2015 through 2022. The cohort comprised 520 low-grade tumors (88.9%) and 65 high-grade tumors (11.1%). High-grade disease was associated with a more advanced pathologic stage distribution and remained independently associated with worse overall and disease-free survival in multivariable analysis.

In patients with pathologic stage IB–III disease who were eligible for adjuvant treatment, there was no overall disease-free survival benefit from adjuvant chemotherapy across the subgroup. When stratified by tumor budding grade, low-grade patients showed no benefit from adjuvant chemotherapy. By contrast, high-grade patients demonstrated a clinically meaningful trend toward benefit, suggesting the grading system may help identify those most likely to gain from postoperative therapy.

Exploratory genomic profiling of a case-matched subset of 100 tumors found no difference in global genomic instability between grades but revealed differences in specific alterations. Low-grade tumors showed significant enrichment of phosphoinositide 3-kinase (PI3K) pathway alterations, while high-grade tumors showed a trend toward enrichment of truncating TP53 mutations. 

Together with the clinical findings, these results suggest that the tumor budding–based grading system provides independent prognostic stratification and is associated with distinct adjuvant chemotherapy outcomes and genomic patterns. The authors called for prospective multicenter validation to establish its role in guiding treatment selection.

“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 of Yonsei University School of Medicine in Seoul, Republic of Korea.

“Prospective multicenter validation will be important to confirm its potential role in treatment selection,” added Hong.

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