Introduction: Although histological subtype in lung adenocarcinoma has been reported as a poor prognostic factor in several studies, its utility has not yet been revealed as an adaptation criterion of postoperative adjuvant chemotherapy. Methods: Four hundred ninety-four lung adenocarcinoma patients were enrolled in this retrospective study. A subanalysis was performed in 420 lung adenocarcinoma patients with pathological stage 0–I disease for risk factors of postoperative recurrence. Results: Maximum standardized uptake value (SUVmax) (p < 0.01), pathological stage ≥II (p < 0.04), and adjuvant chemotherapy (p < 0.01) were risk factors for recurrence in the multivariate analysis, whereas histological subtype was not a significant factor for recurrence at all stages. In the subanalysis, univariate analysis showed that carcinoembryonic antigen expression (p < 0.01), prognostic nutrition index (p = 0.03), SUVmax (p < 0.01), lymphatic invasion (p < 0.01), vascular invasion (p < 0.01), grade 3–4 differentiation (p < 0.01), pathological stage ≥IA3 (p < 0.01), and histological subtype (p = 0.03) were significant risk factors of recurrence. SUVmax (p < 0.01) was the only risk factor for recurrence in the multivariate analysis, whereas histological subtype was not (p = 0.07). Relapse-free survival (RFS) was significantly worse in the micropapillary- and solid-predominant subtype groups than in the other subtypes (p = 0.01). On the other hand, RFS with or without uracil-tegafur as adjuvant chemotherapy in lung micropapillary- or solid-predominant adenocarcinoma patients with pathological stage IA-IB disease was not significantly different. Conclusion: This study suggested that histological subtypes, such as micropapillary- or solid-predominant pattern, are risk factors for recurrence in pathological stage 0-I lung adenocarcinoma and may be necessary adjuvant chemotherapy instead of uracil-tegafur.

1.
Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin. 2018;68(1):7–30.
2.
Travis W, Brambilla E, Noguchi M, Nicholson A, Geisinger K, Yatabe Y, et al. International association for the study of lung cancer/American Thoracic Society/European Respiratory Society international multidisciplinary classification of lung adenocarcinoma. J Thorac Oncol. 2011;6(2):244–85.
3.
Mansuet-Lupo A, Bobbio A, Blons H, Becht E, Ouakrim H, Didelot A, et al. The new histologic classification of lung primary adenocarcinoma subtypes is a reliable prognostic marker and identifies tumors with different mutation status: the experience of a French cohort. Chest. 2014;146(3):633–43.
4.
Zugazagoitia J, Enguita AB, Nuñez JA, Iglesias L, Ponce S. The new IASLC/ATS/ERS lung adenocarcinoma classification from a clinical perspective: current concepts and future prospects. J Thorac Dis. 2014;6(Suppl 5):S526–536.
5.
Russell PA, Wainer Z, Wright GM, Daniels M, Conron M, Williams RA. Dose lung adenocarcinoma subtype predict patient survival? A clinicopathologic study based on the new International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society international multidisciplinary lung adenocarcinoma classification. J Thorac Oncol. 2011;6(9):1496–504.
6.
Motono N, Matsui T, Machida Y, Usuda K, Uramoto H. Prognostic significance of histologic subtype in pStage I lung adenocarcinoma. Med Oncol. 2017;34(6):100.
7.
Zhang Y, li J, Wang R, Li Y, Pan Y, Cai D, et al. The prognostic and predictive value of solid subtype in invasive lung adenocarcinoma. Sci Rep. 2014;4:7163.
8.
Zhao Y, Wang R, Shen X, Pan Y, Cheng C, Li Y, et al. Minor components of micropapillary and solid subtypes in lung adenocarcinoma are predictors of lymph node metastasis and poor prognosis. Ann Surg Oncol. 2016;23(6):2099–105.
9.
Zhang H, Huang W, Liu C, Giaccone G, Zhao X, Sun X, et al. The prognostic value of non-predominant micropapillary pattern in a large cohort of resected invasive lung adenocarcinoma measuring ≤3 cm. Front Oncol. 2021;11:657506.
10.
Jhala H, Harling L, Rodrigo A, Nonaka D, Mclean E, Ng W, et al. Clinicopathological predictors of survival in resected primary lung adenocarcinoma. J Clin Pathol. 2022;75(5):310–5.
11.
Nitadori J, Bograd AJ, Morales EA, Rizk NP, Dunphy MPS, Sima CS, et al. Preoperative consolidation-to-tumor ratio and SUVmax stratify the risk of recurrence in patients undergoing limited resection for lung adenocarcinoma ≤2 cm. Ann Surg Oncol. 2013;20(13):4282–8.
12.
Brinkman GL, Coates EO. The effect of bronchitis, smoking, and occupation on ventilation. Am Rev Respir Dis. 1963;87:684–93.
13.
Li D, Yuan X, Liu J, Li C, Li W. Prognostic value of prognostic nutritional index in lung cancer: a meta-analysis. J Thorac Dis. 2018;10(9):5298–307.
14.
Qiu C, Qu X, Shen H, Zheng C, Zhu L, Meng L, et al. Evaluation of prognostic nutritional index in patients undergoing radical surgery with nonsmall cell lung cancer. Nutr Cancer. 2015;67(5):741–7.
15.
Zahorec R. Ratio of neutrophil to lymphocyte counts: rapid and simple parameter of systemic inflammation and stress in critically ill. Bratisl Lek Listy. 2001;102(1):5–14.
16.
Shimizu K, Okita R, Saisho S, Maeda A, Nojima Y, Nakata M. Preoperative neutrophil/lymphocyte ratio and prognostic nutritional index predict survival in patients with non-small cell lung cancer. J Surg Oncol. 2015;13:291.
17.
Mizuguchi S, Izumi N, Tsukioka T, Komatsu H, Nishiyama N. Neutrophil-lymphocyte ratio predicts recurrence in patients with resected stage 1 non-small cell lung cancer. J Cardiothorac Surg. 2018;13:78.
18.
Kim YS, Kim SJ, Kim YK, Kim IJ, Kim YD, Lee MK. Prediction of survival and cancer recurrence using F-18 FDG PET/CT in patients with surgically resected early stage (stage I and II) non-small cell lung cancer. Neoplasma. 2011;58(3):245–50.
19.
Motono N, Ueno M, Tanaka M, Machida Y, Usuda K, Sakuma T, et al. Differences in the prognostic significance of the SUVmax between patients with resected pulmonary adenocarcinoma and squamous cell carcinoma. Asian Pac J Cancer Prev. 2014;15(23):10171–4.
20.
Felip E, Altorki N, Zhou C, Csőszi T, Vynnychenko I, Goloborodko O, et al. Adjuvant atezolizumab after adjuvant chemotherapy in resected stage IB–IIIA non-small-cell lung cancer (IMpower010): a randomised, multicentre, open-label, phase 3 trial. Lancet. 2021;398(10308):1344–57.
21.
Wu YL, John T, Grohe C, Majem M, Goldman JW, Kim SW, et al. Postoperative chemotherapy use and outcomes from ADAURA: osimertinib as adjuvant therapy for resected EGFR-mutated NSCLC. J Thorac Oncol. 2022;17(3):423–33.
22.
Kato H, Ichinose Y, Ohta M, Hata E, Tsubota N, Tada H, et al. A randomized trial of adjuvant chemotherapy with uracil-tegafur for adenocarcinoma of the lung. N Engl J Med. 2004;350(17):1713–21.
23.
Tsutani Y, Imai K, Ito H, Miyata Y, Ikeda N, Nakayama H, et al. Adjuvant chemotherapy for high-risk pathologic stage I non-small cell lung cancer. Ann Thorac Surg. 2022;113(5):1608–16.
You do not currently have access to this content.