Frozen sections accurately predict the IASLC proposed grading system and prognosis in patients with invasive lung adenocarcinomas

•FS (frozen section) had high diagnostic accuracy for IASLC grading system.•The interobserver agreement for IASLC grading system on FS were satisfactory.•Presence of complex glands were associated with discrepancy between FS and final pathology diagnosis.•The IASLC grading system diagnosed by FS could well stratify prognosis for patients with stage I invasive lung ADC. The International Association for the Study of Lung Cancer (IASLC) newly proposed grading system for lung adenocarcinomas (ADC) has been shown to be of prognostic significance. Hence, intraoperative consultation for the grading system was important regarding the surgical decision-making. Here, we evaluated the accuracy and interobserver agreement for IASLC grading system on frozen section (FS), and further investigated the prognostic performance. FS and final pathology (FP) slides were reviewed by three pathologists for tumor grading in 373 stage I lung ADC following surgical resection from January to June 2013 (retrospective cohort). A prospective multicenter cohort (January to June 2021, n = 212) were included to confirm the results. The overall concordance rates between FS and FP were 79.1% (κ = 0.650) and 89.6% (κ = 0.729) with substantial agreement in retrospective and prospective cohorts, respectively. Presence of complex gland was the only independent predictor of discrepancy between FS and FP (presence versus. absence: odds ratio, 2.193; P = 0.015). The interobserver agreement for IASLC grading system on FS among three pathologists were satisfactory (κ = 0.672 for retrospective cohort; κ = 0.752 for prospective cohort). Moreover, the IASLC grading system by FS diagnosis could well predict recurrence-free survival and overall survival for patients with stage I invasive lung ADC. Our results suggest that FS had high diagnostic accuracy and satisfactory interobserver agreement for IASLC grading system. Future prospective studies are merited to validate the feasibility of using FS to match patients into appropriate surgical type.