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. 2018 Dec;9(12):1594-1602.
doi: 10.1111/1759-7714.12866. Epub 2018 Oct 8.

Increased risk of recurrence in resected EGFR-positive pN0M0 invasive lung adenocarcinoma

Masaoki Ito  1 , Yoshihiro Miyata  1 , Kei Kushitani  2 , Tomoharu Yoshiya  1 , Yuichiro Kai  1 , Yasuhiro Tsutani  1 , Takeshi Mimura  1 , Kazuo Konishi  1 , Yukio Takeshima  2 , Morihito Okada  1
Affiliations

Increased risk of recurrence in resected EGFR-positive pN0M0 invasive lung adenocarcinoma

Masaoki Ito et al. Thorac Cancer. 2018 Dec.

Abstract

Background: This study was conducted to evaluate the prognostic and recurrent impact of EGFR mutation status in resected pN0M0 lung adenocarcinoma with consideration of the histological subtype.

Methods: Following retrospective analysis of whole 474 consecutive pathological N0M0 lung adenocarcinoma patients, the prognostic significance of EGFR mutation status was evaluated in limited 394 subjects. Overall survival and recurrence-free interval (RFI) were estimated using the Kaplan-Meier method and compared using a log-rank test. Univariate and multivariate analyses were performed using Cox proportional hazard models.

Results: The five-year RFI was 85.7% and 93.3% for EGFR positive (n = 176) and negative (n = 218) cases, respectively (hazard ratio [HR] 1.992, 95% confidence interval [CI] 1.005-3.982; P = 0.048). Following the exclusion of specific subtypes free from recurrence or EGFR mutation (adenocarcinoma in situ, minimally invasive adenocarcinoma, and invasive mucinous adenocarcinoma), the five-year RFI was obviously poorer in EGFR positive compared to negative cases (80.7% and 92.1%, respectively; HR 2.163, 95% CI 1.055-4.341; P = 0.035). Multivariate analysis excluding the specific subtypes confirmed that male sex, age, current or Ex-smoking status, pleural invasion, and EGFR-positive status were independently associated with shorter RFI. No significant differences in five-year overall survival were found between the EGFR mutation positive and negative groups (88.7% and 93.7%, respectively; HR 1.630, 95% CI 0.787-3.432; P = 0.2).

Conclusion: EGFR mutations are associated with recurrence in pN0M0 lung adenocarcinoma. EGFR mutation status and histological subtype should be considered when evaluating the risk of recurrence in resected lung adenocarcinoma patients.

Keywords: EGFR mutation; histological subtype; lung adenocarcinoma; recurrence; surgery.

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Figures

Figure 1
Figure 1
Consort diagram of the study.
Figure 2
Figure 2
Frequency of EGFR mutation status according to predominant histological subtype. EGFR positive cases are represented by the blue bar, and EGFR negative by the red bar. (formula image) positive, and (formula image) negative.
Figure 3
Figure 3
Kaplan–Meier curves for overall survival (OS) and recurrence‐free interval (RFI) according to EGFR mutation status. Confidence limits are shown as colored shaded areas. (a) OS and (b) RFI curves of all histological subtypes (n = 394). (c) OS and (d) RFI curves of specific subtypes, excluding adenocarcinoma in situ, invasive mucinous adenocarcinoma, and minimally invasive adenocarcinoma (n = 279). (a) (formula image) Negative 93.7%, (formula image) Positive 88.7%, p = 0.2, (b) (formula image) Negative 93.3%, (formula image) Positive 85.7% p = 0.048, (c) (formula image) Negative 94.1%, (formula image) Positive 86.3% p = 0.3, (d) (formula image) Negative 92.1%, and (formula image) Positive 80.7% p = 0.035.
See this image and copyright information in PMC

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