Prognostic factors of patients with pathologic stage I lung adenocarcinoma

Introduction

Lung cancer remains one of the most common causes of cancer-related deaths worldwide. Increasingly more research is aimed at investigating the clinicopathologic parameters or gene mutations involved in the survival of patients with lung cancer. Although the 5-year survival rate of stage I non-small cell lung cancer (NSCLC) is between 68% and 92% (stage IA1 to IB) (1), there is still much scope for progress. In our previous study (2), we reviewed the predictors of postoperative recurrence in NSCLC and postulated that those results may help optimize patient selection for specified surveillance guidelines and personalized adjuvant therapies to prevent potential occult micrometastases. In Taiwan, lung adenocarcinoma is the most common histologic subtype (12,648/21,536, 58.73%) that had become more prevalent among non-smoking women (3). Moreover, predictors of postoperative outcomes in lung adenocarcinoma have been a popular investigatory target in recent years. Therefore, we used the search engine PubMed and reviewed papers about the risk factors of postoperative outcomes in patients with stage I lung adenocarcinoma (Table 1).

Table 1 Comparison of prognostic factors for patients with stage I lung adenocarcinoma
Full table

Risk factors of postoperative outcomes in pathologic stage I lung adenocarcinoma

We utilized key words such as “predictors” or “risk factors” and “stage I lung adenocarcinoma” in PubMed. Twenty-nine papers were found published between 1994 and 2017. Among these, 21 (72.41%) papers were published in the last 5 years and the patient populations of 22 studies were Asian. Therefore, an increasing number of patients with early-stage lung adenocarcinoma have been treated in the recent decades and therapeutic outcomes are still being investigated. The studies listed in Table 1 provide a broad overview of the geographical distribution and high prevalence of lung adenocarcinoma in Asia.

Micropapillary components were thought as predictors of poor outcomes in patients with stage I lung adenocarcinoma in 4 studies (4-7). They have been proven to reflect an aggressive subtype of lung adenocarcinomas with poor prognosis (33-36). De Oliveira Duarte Achcar et al. (37) concluded that K-ras, EGFR, and BRAF mutations occur at increased frequencies in lung adenocarcinomas showing greater than 75% micropapillary growth. There is a close relationship between histology appearances and gene mutations. Other predictors for pathologic stage I lung adenocarcinoma are clinicopathologic parameters, such as tumor size (4,16), TNM stage (4,13), aerogenous spread (5,9), tumor differentiation (4), bronchial involvement (4), lymphovascular invasion (4,18,23,26), positive thyroid transcription factor-1 (TTF-1) expression (19,28), lepidic growth pattern (16), sex (16), age (22), tumor budding (14), pleural invasion (29), carcinoembryonic antigen levels (30), and standardized uptake value (SUV) index (<1.0) (25). Epigenetic factors or gene mutations involved with surgical outcomes of patients with stage I lung adenocarcinoma include BRCAl (8,20) and ERBB3 (8), K-ras mutation (10,32), HIF1A (20), DLC1 (20), XPO1 (20), MDM2 protein (11), increased nuclear CCND1 (12), tumoral CD10 (15), ACTN4 (17), EGFR (21), Podoplanin-positive CAFs (24), eukaryotic initiation factor 4E and 4E binding protein 1 (eIF4E and 4E-BP1) (27), CD117 (c-kit) (31), and p53 expression (32).

Conclusions

The studies identified in this review concluded many different factors affecting surgical outcomes of patients with stage I lung adenocarcinoma. It is difficult to clarify why these predictors showed different results in various studies. Although there are too many confounding factors, such as patient selection criteria, surgical techniques, or other comorbidities, these pathways could be novel therapeutic strategies for lung adenocarcinoma and these predictors could help in selecting high-risk patients with stage I lung adenocarcinoma for adjuvant therapy, such as target therapy, chemotherapy, radiotherapy, or immunotherapy.

Acknowledgements

None.

Footnote

Conflicts of Interest: The authors have no conflicts of interest to declare.

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