Novel Insights Into the International Association for the Study of Lung Cancer Grading System for Lung Adenocarcinoma

Kay See Tan; Allison Reiner; Katsura Emoto; Takashi Eguchi; Yusuke Takahashi; Rania G Aly; Natasha Rekhtman; Prasad S Adusumilli; William D Travis

doi:10.1016/j.modpat.2024.100520

Novel Insights Into the International Association for the Study of Lung Cancer Grading System for Lung Adenocarcinoma

Mod Pathol. 2024 May 21;37(7):100520. doi: 10.1016/j.modpat.2024.100520. Online ahead of print.

Authors

Kay See Tan¹, Allison Reiner², Katsura Emoto³, Takashi Eguchi⁴, Yusuke Takahashi⁵, Rania G Aly⁶, Natasha Rekhtman⁶, Prasad S Adusumilli⁷, William D Travis⁶

Affiliations

¹ Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York. Electronic address: tank@mskcc.org.
² Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York.
³ Department of Pathology, Keio University School of Medicine, Tokyo, Japan.
⁴ Division of General Thoracic Surgery, Department of Surgery, Shinshu University School of Medicine, Matsumoto, Japan.
⁵ Division of Thoracic Surgery, Jikei Medical University, Tokyo, Japan.
⁶ Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York.
⁷ Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York; Center for Cell Engineering, Memorial Sloan Kettering Cancer Center, New York, New York.

PMID: 38777035
DOI: 10.1016/j.modpat.2024.100520

Abstract

The new grading system for lung adenocarcinoma proposed by the International Association for the Study of Lung Cancer (IASLC) defines prognostic subgroups on the basis of histologic patterns observed on surgical specimens. This study sought to provide novel insights into the IASLC grading system, with particular focus on recurrence-specific survival (RSS) and lung cancer-specific survival among patients with stage I adenocarcinoma. Under the IASLC grading system, tumors were classified as grade 1 (lepidic predominant with <20% high-grade patterns [micropapillary, solid, and complex glandular]), grade 2 (acinar or papillary predominant with <20% high-grade patterns), or grade 3 (≥20% high-grade patterns). Kaplan-Meier survival estimates, pathologic features, and genomic profiles were investigated for patients whose disease was reclassified into a higher grade under the IASLC grading system on the basis of the hypothesis that they would strongly resemble patients with predominant high-grade tumors. Overall, 423 (29%) of 1443 patients with grade 1 or 2 tumors classified based on the predominant pattern-based grading system had their tumors upgraded to grade 3 based on the IASLC grading system. The RSS curves for patients with upgraded tumors were significantly different from those for patients with grade 1 or 2 tumors (log-rank P < .001) but not from those for patients with predominant high-grade patterns (P = .3). Patients with upgraded tumors had a similar incidence of visceral pleural invasion and spread of tumor through air spaces as patients with predominant high-grade patterns. In multivariable models, the IASLC grading system remained significantly associated with RSS and lung cancer-specific survival after adjustment for aggressive pathologic features such as visceral pleural invasion and spread of tumor through air spaces. The IASLC grading system outperforms the predominant pattern-based grading system and appropriately reclassifies tumors into higher grades with worse prognosis, even after other pathologic features of aggressiveness are considered.

Keywords: cribriform; nonmucinous lung adenocarcinoma; pathologic tumor grading; prediction model; spread of tumor through air spaces.