Prognostic effect of adenocarcinoma subtypes in EARLY stage operated lung cancer patients

Adenocarcinoma is the most common subtype of lung cancer. Lung adenocarcinomas are a highly heterogeneous group with five basic histological subtypes, mainly lepidic, acinar, papillary, micropapillary and solid. Most patients have mixed lung adenocarcinoma, and these subtypes are classified according to the predominant type with the most common percentage. Although classification according to the dominant pattern is a prognostic factor in terms of overall survival and recurrence, even cases where high-grade subtypes (such as solid and micropapillary) are not the dominant pattern but are in the tumour structure adversely affect the prognosis. Therefore, it is of great importance to determine the prognosis and the factors predicting recurrence for the control of this disease, which has a high recurrence rate even after curative treatment at an early stage. In our study, it was aimed to investigate the prognostic effect of histological patterns in adenocarcinomas that underwent curative resection at an early stage. 141 patients who underwent curative resection for stage I lung adenocarcinoma in Ankara University Faculty of Medicine, Department of Thoracic Surgery (AUTF) between 2011 and 2019 were evaluated retrospectively. The clinical, laboratory, radiological and pathological data of the patients and the relationship of these data with recurrence and survival were examined. Pathology preparations of the patients were reviewed by two experienced pathologists according to the 2021 World Health Organisation (WHO) classification and the grading system recommended by the 2020 International Association for the Study of Lung Cancer (IASLC) pathology committee. 63% of the patients were male and 37% were female. The mean age was 62 ± 7.8 years. Lobectomy was performed in all patients, and the overall 5-year survival rate was 82.7% in all patients with the survival rate without relapse being 77.6%. The effects of gender, number of lymph nodes sampled, pT stage, F-18 Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (FDG PET/CT) tumor SUVmax uptake, lymphovascular invasion and visceral pleural invasion on the overall survival were found to be statistically significant (p= 0.015, p=0.047, p=0.004, p=0.013, p=0.007, p=0.041, respectively). The effect of tumor SUVmax value of 4.8 and above in FDG PET/CT, presence of STAS, and IASLC Grade 3 and STAS association on recurrence-free survival were statistically significantly worse (p=0.001, p=0.038, p=0.002, respectively). In relapse-free survival analyses with univariate Cox regression, HR was found to be 3.096 for relapse in STAS positivity alone, while it was HR=5.680 for relapse in STAS-positive and IASLC Grade 3 group. Results were significant for both variants (p=0.049 for STAS and p=0.007 for STAS + IASLC Grade), but STAS-positive and Grade 3 tumours were much more at risk for recurrence. Age, gender, and PET/CT SUVmax uptake were statistically significant in the overall survival analyses performed with multivariate Cox regression (p=0.019, p=0.026, p=0.045, respectively). Age, PET/CT SUVmax involvement, and STAS + IASLC Grade combination classification were found to be statistically significant in recurrence-free survival (p=0.015, p=0.005, p=0.021, respectively). In conclusion, the prognostic significance of IASLC Grade 3 tumours and the presence of STAS on recurrence-free survival was confirmed by both univariate and multivariate analyses in our study. Therefore, IASLC Grade 3 and STAS positivity are independent risk factors for poor prognosis and recurrence in patients with resected lung adenocarcinoma. Considering the risk of recurrence after surgical resection in patients with these characteristics, although it is in the early stage, the indication for adjuvant therapy may need to be re-evaluated and a closer follow-up protocol should be applied.