Clinical Effectiveness of Tumor Markers (CEA, NSE, Cyfra 21-1) in Completely Resected Non-small Cell Lung Cancer

Seok Jin Haam; Gil Dong Kim; Sang Ho Cho; Doo Yun Lee

doi:10.6058/jlc.2006.5.2.75

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Haam, Kim, Cho, and Lee: Clinical Effectiveness of Tumor Markers (CEA, NSE, Cyfra 21-1) in Completely Resected Non-small Cell Lung Cancer

Original Article

J Lung Cancer 2006;5(2):75-83.

Published online: 18 December 2006

DOI: https://doi.org/10.6058/jlc.2006.5.2.75

Clinical Effectiveness of Tumor Markers (CEA, NSE, Cyfra 21-1) in Completely Resected Non-small Cell Lung Cancer

Seok Jin Haam, M.D., Gil Dong Kim, M.D.¹, Sang Ho Cho, M.D.², Doo Yun Lee, M.D.

¹Department of Thoracic and Cardiovascular Surqerv. Yonadona Severance Hospital, Yonsei University College of Medicine, Department of Thoracic and Cardiovascular Suraerv, Eulii University Hospital. Eulii University

²department of Patholoav, Severance Hosoital. Yonsei University College of Medicine, Seoul, Korea

Address for correspondence Doo Yun Lee. M.D. Department of Thoracic and Cardiovascular Suraerv, Yonadona Severance Hospital, Yonsei University Colleqe of Medicine. 146-92, Doaok-dona. Gangnam- au. Seoul 135-720, Korea Tel: 82-2-2019-3380 Fax; 82-2-3461·滷2 E-mail: dylee@yumc.yonsei.ac.kr

Received 12 January 2006 Accepted 15 December 2006

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Purpose:

The applicability of tumor markers still remains controversial in non-small ceil lung cancer (NSCLC) due to lower sensitivity & specificity. And, tumor markers actually have not been used determining treatment plans in NSCLC patients yet. So, we evaluated correlation between levels of serum tumor marker (CEA, NSE and Cyfra 21-1) and prognosis in NSCLC patients underwent complete surgical resection.

Materials and Methods:

We retrospectively studied 64 NSCLC patients underwent complete surgical resection in Yongdong severance hospital from April 2002 to October 2005. Preoperative and postoperative serum levels of tumor markers (CEA, NSE, Cyfra 21-1) were measured with commercialized kits and the correlation between the serum levels of tumor markers and prognosis was evaluated. Normal cutoff values of CEA, NSE and Cyfra 21-1 were 5.0 ng/ml, 12.5 ng/ml and 3.2 ng/ml. We estimated recurrence or distant metastasis with computed tomography, magnetic resonance imaging, whole body bone scan, positron emission tomography and biopsy.

Results:

Preoperative and postoperative serum levels of tumor markers were not significantly correlated with lung cancer stages and histologies. The elevated levels of postoperative CEA (p=0.0142) and Cyfra 21-1 (p=0,0105) were correlated with shortened survival time. And, the shortened disease free interval was significantly associated with the elevated level of postoperative Cyfra 21-1 (p=0.0018). The elevated level of preoperative Cyfra 21-1 (p=0.ᄋ566) had a tendency to relate the shortened survival time, but it didn't reach statistical importance

Conclusion:

Considering previous results, especially Cyfra 21-1 may be useful prognostic factor in predicting survival times, and recurrence or metastasis. But, further study and longer follow-up period were needed to make conclusion regarding usefulness of other t䴸mor markers. (J Lung Cancer 20Q6;5(2):75-83)

Keywords: Non-small cell lung cancer, Tumor markers, CEA, NSE, Cyfra 21-1

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Fig. 1.

Survivals according to preoperative serum tumour markers. There was no correlation between serum tumour marker corxntrations and survival. The elevated level of Cyfra 21-1 had a tendency to relate shortened survival time. But, it didn't reach statistical importance (C).

Fig. 2.

Survivals according to postoperative serum tumor markers. The elevated levels of serum CEA (A) and Cyfra 21-1 (CI were significantly correlated with shortened survival. But, The level of serum NSE was not correlated with survival time.

Fig. 3.

Disease free intefval according to preoperative serum tumour markers. There was no correlation between serum tumour marker concentrations and disease free interval.

Fig. 4.

Disease free interval according to postoperative serum tumour markers. Only high serum Cyfra 21-1 (C) level was significantly correlated with shortened disease free interval The levels of CEA and Cyira 21-1 were not correlated with disease free interval

Table 1.

Characteristics of Patients

Characteristic	No (%)
Number of patients	64
Aae (meanSD, year)	55.59.2
Sex
Male	4S (75.0)
Female	16 (25.0)
Histological types
Squamous cell carcinoma	16 (25.0)
Adenocarcinoma	37 (57.8)
Bronchoalveolar cell carcimona	1 (1.6)
Adenosquamous cell carcinoma	2 (3.1)
Large cell carcimona	1 (1.6)
Carcinoid	1 (1.6)
Others	6 (9.4)
Pathologic stage
la	15 (23.4)
lb	14 (21.9)
lla	2 (3.1)
llb	15 (23.4)
llla	13 (20.3)
lllb	5 (7.8)
Types of surgery
Pneumonectomy	15 (23.4)
Lobectomy	38 (59,4)
Bilobectomy	9 (14.1)
Wedge resection	2 (3.1)

Table 2.

Mean Values of Preoperative and Postoperative Serum Tumor Markers

	MeanSD (ng/ml)
	CEA	NSE	Cyfra 21-1
Preoperative
Normal level group	2.30.1	9.10.2	2.20.1
Higher level group	30.911.0	15.50.8	7.31.3
Postoperative
Normal level group	2.40.1	9.10.2	1.60.1
Higher level group	22.310.4	22.41	6.11.1

Table 3.

Comparison between Preoperative and Postoperative Levels of CEA, NSE and Cyfra 21-1

Tumor marker	MeanSD [range] (ng/ml)		ρ value
Tumor marker	Preoperative	Postoperative	ρ value
CEA	10.727.3 [0.8~172.1]	4.610.6 [0.8~80.1]	0.008
NSE	10.33.2 [5.3~22.7]	12.014.8 [5.0~127.1]	0.370
Cyfra 21-1	3.03.0 [0.6~8.7]	2.11.8 [0.5~10.1]	0.018

Table 4.

Mean Values of Preoperative Serum Tumor Markers according to Pathologic Stage & Histologic Type

Characteristic	Mean + SD (na/ml)
Characteristic	CEA	NSE	Cyfra 21-1
Pathologic stage
l	6.38.3	10.02.9	2.32.2
ll	17.841.4	9.93.1	3.84.2
llla	14.036.3	11.03.9	3.73.3
lllb	3.94.0	11.53.9	2.20.7
p value	0.223	0.666	0.169
Histological types
Squamous cell carcinoma	6.58.6	10.53.4	3.01.6
Adenocarcinoma	14.135.1	10.23.4	2.52.2
p value	0.504	0.614	0.069

Table 5.

Comparison of Serum Tumor Marker Levels among Relapse Sites

Tumor marker	MeanSD [range] (ng/ml)		p value
Tumor marker	Lung	Other sites	p value
Preoperative
CEA	2.30.9 [1.2~3.6]	17.637.3 [1.9~134.5]	0.010
NSE	11.33.7 [7.4~17.6]	9.22.7 [5.3~15.4]	0.181
Cyfra 21-1	1.60.8 [0.6~3.0]	4.03.2 [1.7~12.4]	0.005
Postoperative
CEA	1.70.7 [0.8~2.7]	6.29.4 [1.6~35.6]	0.002
NSE	26.940.5 [9.0~127.1]	7.91.3 [5.0~9.9]	0.000
Cyfra 21-1	1.50.8 [0.5~2.6]	3.22.6 [0.8~9.8]	0.115

Table 6.

Comparison of Serum Tumor Marker Levels between Relapse Group and Non-relapse Group

Tumor marker	MeanSD [range] (ng/ml)		p value
Tumor marker	Relapse group	Non-relapse group	p value
Preoperative
CEA	11.529.4 [12~134.5]	10.426.7 [0.8~172.1]	0.577
NSE	10.03.2 [5.3~17.6]	10.43.2 [5.4~22.7]	0.447
Cyfra 21-1	3.02.8 [0.6~12.4]	3.03.2 [1.0~18.7]	0.638
Postoperative
CEA	4.47.5 [0.8~35.6]	4.711.8 [05~80.1]	0.868
NSE	15.526.4 [5.0~127.1]	10.42.5 [6.9~17.8]	0.297
Cyfra 21-1	2.52.2 [0.5~9.8]	1.91.5 [0.5~10.1]	0.425

Table 7.

Follow Up of Serum Tumor Markers and Timing of Recurrence

Patient/time		1st	2nd	3rd	4th	5th	6th	7th
1	CEA	2.3	3.3	2.9	2.2	3.0	*3.0*
	NSE	14.2	12.8	13.4	13.2	14.1	*13.6*
	Cyfra 21-1	2.8	3.1	2.9	2.0	1.5	*1.7*
2	CEA	4.6	3.8	*3.3*	5.5
	NSE	10.1	16.6	*9.3*	15.2
	Cyfra 21-1	2.8	1.8	*1.0*	1.2
3	CEA	1.4	1.5	1.7	*1.7*	1.9	1.9	1.6
	NSE	6.4	5.7	5.9	*5.7*	5.7	5.1	7.3
	Cyfra 21-1	4.0	2.6	1.5	*2.4*	2.0	2.4	1.4
4	CEA	2.4	4.2	*3.5*	5.9
	NSE	8.6	8.2	*11.1*	5.6
	Cyfra 21-1	0.8	0.6	*1.7*	2.5
5	CEA	2.2	*2.1*	4.5	3.7
	NSE	9.9	*12.7*	13.1	13.6
	Cyfra 21-1	3.7	*2.9*	3.4	3.2
6	CEA	2.3	*1.8*	1.9	2.5
	NSE	11.3	*12.5*	13.2	13.6
	Cyfra 21-1	1.8	*1.3*	1.8	2.0
7	CEA	1.0	*2.6*	*3.5*	3.8
	NSE	6.1	6.1	*7.6*	7.3
	Cyfra 21-1	1.4	1.2	*2.2*	2.4
8	CEA	*3.4*	3.1	7.0
	NSE	*15.5*	17.5	20.5
	Cyfra 21-1	*11.0*	13.3	11.5
9	CEA	2.4	*7.4*	16.6
	NSE	7.8	*7.9*	9.9
	Cyfra 21-1	1.0	*2.6*	2.2

Italic letters timing of recurrence, unit (ng/ml)

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