Abstract
Background
This study aimed to evaluate the dynamic impact of the micropapillary (MIP) component on local recurrence (LR), distant metastasis (DM), and multiple recurrence (MR) of pathological stage IA3 lung adenocarcinoma.
Methods
Between July 2012 and July 2020, a total of 351 patients at two medical institutions were enrolled in this study. Cumulative incidence of curves, dynamic risk curves, and time-dependent multivariate analysis was performed to evaluate the effect of the MIP component on patients.
Results
The 5-year cumulative incidence of total recurrence with or without an MIP component was 34.2% and 12.3%, respectively (p = 0.001). In three recurrence patterns, our findings revealed that the 5-year cumulative incidence of LR (p = 0.048) and DM (p = 0.005) was higher in the ‘MIP-present’ group than in the ‘MIP-absent’ group. In the dynamic recurrence curve, the risk of the three recurrence patterns was different and varied over time between the two groups, especially in DM. Moreover, the dynamic cumulative event curve showed that after 1, 2, and 3 years of survival, the cumulative incidence of DM in the group with MIP continued to be higher than that in the group without MIP (all p < 0.05). Time-dependent Cox regression analysis indicated that the MIP component continued to be an independent risk factor for the cumulative incidence of DM in patients with 3-year survival.
Conclusions
Of the three recurrence patterns, the MIP component mainly aggravated the risk of DM in patients with pathological stage IA3 lung adenocarcinoma, which persisted for 3 years.
Similar content being viewed by others
Data availability
The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.
References
Houston KA, Mitchell KA, King J, White A, Ryan BM. Histologic lung cancer incidence rates and trends vary by race/ethnicity and residential county. J Thoracic Oncol. 2018;13(4):497–509.
Bray F, Ferlay J, Laversanne M, Brewster DH, Gombe Mbalawa C, Kohler B, Piñeros M, Steliarova-Foucher E, Swaminathan R, Antoni S, et al. Cancer incidence in five continents: Inclusion criteria, highlights from volume X and the global status of cancer registration. Int J Cancer. 2015;137(9):2060–71.
Kelsey CR, Fornili M, Ambrogi F, Higgins K, Boyd JA, Biganzoli E, Demicheli R. Metastasis dynamics for non-small-cell lung cancer: effect of patient and tumor-related factors. Clin Lung Cancer. 2013;14(4):425–32.
Watanabe K, Tsuboi M, Sakamaki K, Nishii T, Yamamoto T, Nagashima T, Ando K, Ishikawa Y, Woo T, Adachi H, et al. Postoperative follow-up strategy based on recurrence dynamics for non-small-cell lung cancer. Eur J Cardio-thoracic Surg. 2016;49(6):1624–31.
Arbour KC, Riely GJ. Systemic therapy for locally advanced and metastatic non-small cell lung cancer: a review. JAMA. 2019;322(8):764–74.
Shi Y, Chen G, Wang X, Liu Y, Wu L, Hao Y, Liu C, Zhu S, Zhang X, Li Y, et al. Furmonertinib (AST2818) versus gefitinib as first-line therapy for Chinese patients with locally advanced or metastatic EGFR mutation-positive non-small-cell lung cancer (FURLONG): a multicentre, double-blind, randomised phase 3 study. Lancet Respirat Med. 2022;10(11):1019–28.
Soria JC, Wu YL, Nakagawa K, Kim SW, Yang JJ, Ahn MJ, Wang J, Yang JC, Lu Y, Atagi S, et al. Gefitinib plus chemotherapy versus placebo plus chemotherapy in EGFR-mutation-positive non-small-cell lung cancer after progression on first-line gefitinib (IMPRESS): a phase 3 randomised trial. Lancet Oncol. 2015;16(8):990–8.
Travis WD, Garg K, Franklin WA, Wistuba II, Sabloff B, Noguchi M, Kakinuma R, Zakowski M, Ginsberg M, Padera R, et al. Evolving concepts in the pathology and computed tomography imaging of lung adenocarcinoma and bronchioloalveolar carcinoma. J Clin Oncol. 2005;23(14):3279–87.
Travis WD, Brambilla E, Noguchi M, Nicholson AG, Geisinger KR, Yatabe Y, Beer DG, Powell CA, Riely GJ, Van Schil PE, et al. International association for the study of lung cancer/american thoracic society/european respiratory society international multidisciplinary classification of lung adenocarcinoma. J Thoracic Oncol. 2011;6(2):244–85.
Zhao Y, Wang R, Shen X, Pan Y, Cheng C, Li Y, Shen L, Zhang Y, Li H, Zheng D, 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.
Cha MJ, Lee HY, Lee KS, Jeong JY, Han J, Shim YM, Hwang HS. Micropapillary and solid subtypes of invasive lung adenocarcinoma: clinical predictors of histopathology and outcome. J Thoracic Cardiovascular Surg. 2014;147(3):921-928.e922.
Demicheli R, Fornili M, Ambrogi F, Higgins K, Boyd JA, Biganzoli E, Kelsey CR. Recurrence dynamics for non-small-cell lung cancer: effect of surgery on the development of metastases. J Thoracic Oncol. 2012;7(4):723–30.
Watanabe K, Sakamaki K, Ito H, Yokose T, Yamada K, Nakayama H, Masuda M. Impact of the micropapillary component on the timing of recurrence in patients with resected lung adenocarcinoma. Eur J Cardio-thoracic Surg. 2020;58(5):1010–8.
Tsutani Y, Imai K, Ito H, Miyata Y, Ikeda N, Nakayama H, Okada M. Adjuvant chemotherapy for high-risk pathologic stage i non-small cell lung cancer. Ann Thoracic Surg. 2022;113(5):1608–16.
Tsutani Y, Ito M, Shimada Y, Ito H, Ikeda N, Nakayama H, Okada M. The impact of epidermal growth factor receptor mutation status on adjuvant chemotherapy for patients with high-risk stage I lung adenocarcinoma. J Thoracic Cardiovascular Surg. 2022;164(5):1306-1315.e1304.
Motoi N, Szoke J, Riely GJ, Seshan VE, Kris MG, Rusch VW, Gerald WL, Travis WD. Lung adenocarcinoma: modification of the 2004 WHO mixed subtype to include the major histologic subtype suggests correlations between papillary and micropapillary adenocarcinoma subtypes, EGFR mutations and gene expression analysis. Am J Surg Pathol. 2008;32(6):810–27.
Kishi N, Ito M, Miyata Y, Kanai A, Handa Y, Tsutani Y, Kushitani K, Takeshima Y, Okada M. Intense expression of EGFR L858R characterizes the micropapillary component and l858r is associated with the risk of recurrence in pN0M0 lung adenocarcinoma with the micropapillary component. Ann Surg Oncol. 2020;27(3):945–55.
Okada M, Nakayama H, Okumura S, Daisaki H, Adachi S, Yoshimura M, Miyata Y. Multicenter analysis of high-resolution computed tomography and positron emission tomography/computed tomography findings to choose therapeutic strategies for clinical stage IA lung adenocarcinoma. J Thoracic Cardiovascular Surg. 2011;141(6):1384–91.
Ettinger DS, Wood DE, Aisner DL, Akerley W, Bauman J, Chirieac LR, D’Amico TA, DeCamp MM, Dilling TJ, Dobelbower M, et al. Non-small cell lung cancer, version 5, NCCN clinical practice guidelines in oncology. J National Comprehen Cancer Netw. 2017;15(4):504–35.
Vansteenkiste J, Crinò L, Dooms C, Douillard JY, Faivre-Finn C, Lim E, Rocco G, Senan S, Van Schil P, Veronesi G et al. 2nd ESMO Consensus Conference on Lung Cancer: early-stage non-small-cell lung cancer consensus on diagnosis, treatment and follow-up. Ann Oncol. 2014;25(8):1462-1474.
Jaklitsch MT, Jacobson FL, Austin JH, Field JK, Jett JR, Keshavjee S, MacMahon H, Mulshine JL, Munden RF, Salgia R, et al. The American association for thoracic surgery guidelines for lung cancer screening using low-dose computed tomography scans for lung cancer survivors and other high-risk groups. J Thoracic Cardiovascular Surg. 2012;144(1):33–8.
Yun JK, Lee GD, Choi S, Kim YH, Kim DK, Park SI, Kim HR. Various recurrence dynamics for non-small cell lung cancer depending on pathological stage and histology after surgical resection. Trans Lung Cancer Res. 2022;11(7):1327–36.
Kamiya K, Hayashi Y, Douguchi J, Hashiguchi A, Yamada T, Izumi Y, Watanabe M, Kawamura M, Horinouchi H, Shimada N, et al. Histopathological features and prognostic significance of the micropapillary pattern in lung adenocarcinoma. Modern pathology. 2008;21(8):992–1001.
Kamigaichi A, Tsutani Y, Mimae T, Miyata Y, Shimada Y, Ito H, Nakayama H, Ikeda N, Okada M. The prognostic impact of the ground-glass opacity component in nearly pure-solid stage IA non-small-cell lung cancer. Eur J Cardio-thoracic Surg. 2022;62(3):166.
Shigefuku S, Shimada Y, Hagiwara M, Kakihana M, Kajiwara N, Ohira T, Ikeda N. Prognostic significance of ground-glass opacity components in 5-Year survivors with resected lung adenocarcinoma. Ann Surg Oncol. 2021;28(1):148–56.
Maeda R, Yoshida J, Hishida T, Aokage K, Nishimura M, Nishiwaki Y, Nagai K. Late recurrence of non-small cell lung cancer more than 5 years after complete resection: incidence and clinical implications in patient follow-up. Chest. 2010;138(1):145–50.
Hedley BD, Chambers AF. Tumor dormancy and metastasis. Adv Cancer Research. 2009;102:67–101.
Funding
This study was supported by grants from the key laboratory of cardio-thoracic surgery (fujian medical university), fujian province university (no. 0713304); the natural science foundation in fujian province (no. 2020j011004); the fujian provincial health technology project (no. 2020cxa028); the cohort study of the school of public health, fujian medical university (no. 2021hx003); the joint funds for the innovation of science and technology, fujian province (no. 2020y9076); and the national nature science foundation of china (no. 82273415).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Disclosure
Shao-jun Xu, Chao Chen, Jia-hua Tu, Cheng-xiong You, Rui-qin Chen, Zhi-fan Zhang, and Shu-chen Chen declare no potential conflicts of interest.
Ethics statement
This study was reviewed and approved by the Institutional Ethics Review Committee of the Fujian Medical University Union Hospital
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary Information
Below is the link to the electronic supplementary material.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Xu, Sj., Chen, C., Tu, Jh. et al. Dynamic Analysis of the Impact of Micropapillary Component on Different Recurrence Patterns of Pathological Stage IA3 Lung Adenocarcinoma: A Multicenter, Retrospective Study. Ann Surg Oncol 31, 872–882 (2024). https://doi.org/10.1245/s10434-023-14520-1
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1245/s10434-023-14520-1