A tumor budding–based grading system was able to successfully identify patients with resected lung squamous cell carcinoma who were at a higher risk of poor overall survival and relapse-free survival outcomes, according to findings presented at the International Association for the Study of Lung Cancer (IASLC) 2026 World Conference on Lung Cancer (WCLC; Abstract MO05.05). The system was also potentially beneficial in helping to guide the use of 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 a poorer prognosis, while also suggesting that high-grade patients may be the group most likely to derive benefit from adjuvant chemotherapy,” said Tae Hee Hong, MD, PhD, Assistant Professor in the Department of Thoracic and Cardiovascular Surgery at Yonsei University School of Medicine in Seoul. “Prospective multicenter validation will be important to confirm its potential role in treatment selection.”
Background and Study Methods
In September 2025, the IASLC's Pathology Committee proposed a two-tier grading system for resected lung squamous cell carcinoma based on tumor budding. Multi-institutional analysis demonstrated the prognostic value of the approach, but independent external validation in a real-world clinical setting was not conducted, and assessment of its predictive value for determining adjuvant chemotherapy benefit was not addressed due to absent treatment data.
The researchers noted that this study attempted to fill both of these gaps.
They retrospectively reviewed 611 consecutive patients with lung squamous cell carcinoma who had undergone curative-intent upfront resection at Yonsei University Medical Center between 2015 and 2022. Excluded patients included those receiving neoadjuvant therapy with in-hospital mortality or follow-up of less than 3 months as well as those with combined histology or unexpected pleural seeding.
Tumor budding was independently assessed by two thoracic pathologists and discordant cases were reviewed and resolved by consensus. Low-grade tumors were considered those with less tumor budding than 10/0.785 mm2 and high-grade tumors were those with tumor budding of 10/0.785 mm2 or higher.
The primary endpoints were overall survival and relapse-free survival. A prespecified subgroup analysis also explored adjuvant chemotherapy benefit in patients with pathologic stage IB–III disease (n = 396).
Key Findings
Eighty-eight percent of the included patients had low-grade tumors. High-grade tumors were associated with significantly more advanced pathologic stage distribution (P < .001).
High-grade tumors were independently associated with worse overall survival outcomes (hazard ratio [HR] = 1.63; 95% confidence interval [CI] = 1.14–2.31; P = .007) and relapse-free survival outcomes (HR = 1.69; 95% CI = 1.13–2.55; P = .011). These tumors were also an independent predictor of overall survival on multivariable analysis (HR = 1.54; 95% CI = 1.07–2.21; P = .021).
Among patients in the subgroup eligible for adjuvant chemotherapy, no relapse-free survival benefit was noted (P = .99).
Grade-stratified analysis found a pattern in which no benefit was seen in patients with low-grade tumors (HR = 1.17; 95% CI = 0.79–1.74; P = .43), but benefit was selectively seen in patients with high-grade tumors (HR = 0.54; 95% CI = 0.22–1.13; P = .086).
“These findings confirm real-world reproducibility of the grading system and suggest its potential as a predictive tool for adjuvant treatment selection, one of the key unmet need of the original IASLC proposal,” the study authors concluded.
DISCLOSURES: For full disclosures of the study authors, visit abstractsonline.com.
