The International Association for the Study of Lung Cancer (IASLC) introduced a validated two-tier tumor budding-based grading system at the IASLC 2026 World Conference on Lung Cancer in Seoul, successfully identifying resected lung squamous cell carcinoma patients at high risk for poor survival outcomes and guiding adjuvant chemotherapy selection.
Validating the Two-Tier Grading Architecture
A retrospective study presented at the IASLC 2026 World Conference on Lung Cancer addresses this diagnostic gap by independently validating the 2025 IASLC two-tier grading system. The framework classifies resected lung SqCC strictly as low grade or high grade based on tumor budding.
Investigators at Yonsei University Medical Center reviewed 585 consecutive patients who underwent curative-intent upfront resection between 2015 and 2022, according to reporting from Mirage News. Out of this cohort, 520 patients—representing 88.9 percent of the total—exhibited low-grade tumors. Meanwhile, 65 patients, or 11.1 percent, presented with high-grade disease. The data revealed a direct correlation between high-grade classification and a significantly more advanced pathologic stage distribution.
Multivariable analysis confirmed that high-grade tumors were independently associated with worse overall survival and disease-free survival.
Guiding Adjuvant Chemotherapy in High-Risk Cohorts
Beyond prognostic categorization, the grading system holds direct clinical implications for post-surgical therapeutic regimens. Investigators specifically analyzed patients with pathologic stage IB through III disease who were eligible for adjuvant treatment.
Across that broader subgroup, the data showed no overall disease-free survival benefit from adjuvant chemotherapy on an aggregate level. However, stratifying the cohort by tumor budding grade altered the clinical picture. Low-grade patients derived no measurable benefit from chemotherapy, whereas high-grade patients demonstrated a clinically meaningful trend toward benefit from adjuvant chemotherapy.
“Our findings show that the newly proposed IASLC tumor budding-based grading system can identify patients with resected lung squamous cell carcinoma who have poorer prognosis, while also suggesting that high-grade patients may be the group most likely to derive benefit from adjuvant chemotherapy,” stated T.H. Hong of Yonsei University School of Medicine in Seoul, Republic of Korea, as reported by Mirage News.
Divergent Oncogenic Programs and Genomic Signatures
To understand the molecular underpinnings driving these clinical differences, researchers conducted exploratory genomic profiling on a case-matched subset of 100 patients. The molecular analysis exposed contrasts in how low-grade and high-grade tumors evolve.
Global genomic instability rates showed no difference across both grades. Instead, the profiling exposed precise pathway divergence:
- Low-grade tumors showed significant enrichment of PI3K pathway alterations.
- High-grade tumors exhibited directional enrichment of truncating TP53 mutations.
These molecular divergences indicate that low-grade and high-grade lung squamous cell carcinomas utilize divergent oncogenic programs to drive disease progression. Recognizing these distinct pathways reinforces the biological validity of the budding-based grading structure.
Next Steps for Clinical Integration
“Prospective multicenter validation will be important to confirm its potential role in treatment selection,” Hong noted regarding the necessity of upcoming clinical trials.
