Gen Thorac Cardiovasc Surg (2009) 57:303–306
DOI 10.1007/s11748-008-0397-6
ORIGINAL ARTICLE
Serum carcinoembryonic antigen level in non-small-cell lung cancer
patients with preoperative normal serum level
Masaki Tomita, MD, PhD · Tetsuya Shimizu, MD, PhD
Masaki Hara, MD, PhD · Takanori Ayabe, MD, PhD
Toshio Onitsuka, MD, PhD
Received: 20 August 2008 / Accepted: 26 December 2008
© The Japanese Association for Thoracic Surgery 2009
Abstract
Objective. The prognostic significance of serum carcino-
embryonic antigen (CEA) levels in non-small-cell lung
cancer (NSCLC) patients with a normal serum CEA
level (<5.0 ng/ml) was examined.
Methods. A total of 220 consecutive NSCLC patients
with preoperative normal serum CEA levels were
included. Patients were subdivided into two groups: pre-
operative serum CEA level ≥2.5 and <2.5 ng/ml.
Results. The 5-year survival of patients with preopera-
tive serum CEA level less and more than 2.5 ng/ml were
79.62% and 62.0%, respectively (P = 0.0036). Multi-
variate analysis indicated that a preoperative serum
CEA level of ≥2.5 ng/ml was an independent prognostic
factor. Similar results were found in patients with adeno-
carcinoma but not found in others.
Conclusion. NSCLC patients with a high serum CEA
level, especially adenocarcinoma patients, had poorer
prognosis even if their serum CEA levels were within the
normal upper limit.
Key words Carcinoembryonic antigen (CEA) · Non-
small-cell lung cancer · Preoperative · Normal level ·
Survival
Introduction
Several previous reports have indicated that preopera-
tive elevated serum carcinoembryonic antigen (CEA)
M. Tomita (*) · T. Shimizu · M. Hara · T. Ayabe · T. Onitsuka
Department of Surgery II, Faculty of Medicine, University of
Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692, Japan
Tel. +81-985-85-2291; Fax +81-985-85-5563
e-mail: mtomita@med.miyazaki-u.ac.jp
levels are associated with more advanced disease and
with very poor survival rates following surgical resection
in non-small-cell lung cancer (NSCLC).1–7 Most of these
studies examined the prognostic significance of serum
CEA level using a comparison of the patients with ele-
vated and normal serum CEA levels based on the cutoff
value. In general, the cutoff value is defined according
to the 95th percentile of healthy individuals. Therefore,
the real cutoff value of the serum CEA level when the
study population is limited to cancer patients is unknown.
There is a possibility that another cutoff value of serum
CEA exists that could be used to identify patients with
an extremely high probability of long-term survival.
Sawabata et al.8 defined another cutoff value as 2.5 ng/
ml, and they named it the “subnormal level.” Although
the exact mechanism of elevated serum CEA levels in
NSCLC remains unclear, the source of CEA production
might be tumor cells; and the CEA itself might enhance
the malignant process of tumor cells.9 Taken together,
we hypothesized that patients with higher serum CEA
levels had poorer prognosis even if their serum CEA
levels were within the normal upper limit. Therefore, this
retrospective study aimed at investigating whether serum
CEA levels predicted favorable survival for patients with
preoperative normal serum CEA levels.
Materials and methods
The present retrospective study was conducted from
1997 through 2004 and included all patients with NSCLC
who had undergone a thoracotomy for intended surgical
resection. Patients who had preoperative chemotherapy
or radiotherapy were excluded. A total of 220 consecu-
tive NSCLC patients with preoperative normal serum
304 Gen Thorac Cardiovasc Surg (2009) 57:303–306

Table 1 Clinicopathological characteristics

Characteristic CEA ≥ 2.5 ng/ml CEA < 2.5 ng/ml P

Age (years)
≥65 42 48 0.070
<65 78 52
Sex
Male 84 46 0.001
Female 36 54
Histology
Adenocarcinoma 87 78 0.434
Other 33 22
Stage
I 78 76 0.206
II 20 12
III–IV 22 12
pT
1 58 64 0.028
2–4 62 36
pN
0 90 83 0.086
1–2 30 17
Smoking
Never 53 42 0.0011
Current/former 47 78
CEA, carcinoembryonic antigen

CEA levels who underwent surgical resection were

included in this study. There were 130 men and 90
women, with ages ranging from 20 to 90 years (average
65 years).
The baseline characteristics are summarized in
Table 1. The clinical investigation section of our hospital
measured serum CEA levels using the two-site immuno-
enzymometric assay; the normal upper limit for this
assay was 5.0 ng/ml. Pathologic (p) TNM staging was
recorded in all patients.
Data between the two groups were compared using
Fisher’s exact test. Survival curves were obtained accord-
ing to the Kaplan-Meier method. Comparison of sur-
vival curves was carried out using the log-rank test. Fig. 1 Survival of patients based on the preoperative serum car-
Statistical calculations were conducted with JMP (SAS cinoembryonic antigen (CEA) level
Institute, Cary, NC, USA), and values of P < 0.05 were
accepted as significant.
The 5-year survival of patients with preoperative
serum CEA level less and more than 2.5 ng/ml were
Results 79.62% and 62.0%, respectively. As shown in Fig. 1,
patients with a preoperative serum CEA level ≥2.5 ng/ml
The preoperative serum CEA levels of all patients were had a poor prognosis despite the fact that their
<5.0 ng/ml (average 2.7 ng/ml). As shown in Table 1, serum CEA levels were within normal upper limit
most of our patients had adenocarcinoma (165/220) and (P = 0.0036).
stage I (154/220) disease. Based on the previous report,8 The results of the univariate analysis are summarized
patients were subdivided into two groups: preoperative in Table 2. The histological subtype (adenocarcinoma
serum CEA level ≥2.5 ng/ml and <2.5 ng/ml. As shown vs. others), pT status (pT1 vs. pT2–4), pN status (pN0
in Table 1, the clinicopathological data were similar for vs. pN1–2), and preoperative serum CEA level (≥2.5 ng/
the two groups, except their smoking habits. ml vs. >2.5 ng/ml) were related to patients’ prognosis