A preliminary study on the consistency between the non-surgical staging and the surgical–pathological staging in oesophageal carcinoma

Abstract

OBJECTIVES

To evaluate the consistency between the clinical staging of non-surgically treated oesophageal carcinoma (preliminary draft) and the surgical–pathological staging of the oesophageal carcinoma.

METHODS

Comprehensive clinical data from 112 patients with oesophageal cancer were collected from January 2009 to June 2010. Based on the clinical staging standard for oesophageal carcinomas treated with non-surgical methods, the preoperative TNM staging was performed and the results were compared with pTNM. The Kappa statistic was used to analyse the degree of consistency.

RESULTS

The Kappa values from the T staging, N staging and TNM staging of surgical–pathological results were 0.545, 0.615 and −0.090, respectively.

CONCLUSIONS

Consistency was observed between the non-surgical T staging and N staging and the postoperative pathological T staging and N staging, but the degree of consistency was only moderate. Additionally, no consistency was observed between the TNM staging results from the two staging systems. Whether the non-surgical staging system can replace the pathological staging system and its significance in evaluating the prognosis remain to be determined.

INTRODUCTION

TNM Staging Standard for Malignant Tumors (the 4th edition), published by the Union for International Cancer Control (UICC) and the American Joint Committee on Cancer (AJCC), is a regularly updated manual for the classification of malignant tumours. It was intended to formulate a unified standard for the staging of tumours, in order to optimize treatment plans, facilitate prognosis and compare treatment effects. Currently, the TNM staging is widely used throughout the world. The latest version of the TNM staging for oesophageal carcinoma, the 7th edition, was issued in 2009. Unfortunately, the TNM staging cannot be applied in patients with an inoperable oesophageal carcinoma. The Clinical Staging Standard for Esophageal Carcinoma Treated with Non-Surgical Methods (draft) was proposed by an expert panel, and published in the Chinese Journal of Radiation Oncology in 2010. Presently, the draft is in trial in China, but specific staging and other criteria lack high-level evidence and remain controversial. Thus, the accuracy of this clinical staging system remains to be further verified. The aim of this study was to compare the pathological staging with the new clinical staging system in order to determine its significance in clinical practice. Currently, all staging systems for the oesophageal carcinoma are pathological. Clinically, in many patients who are diagnosed with oesophageal carcinoma, surgery is not an option; therefore, chemoradiation is the best choice for these patients. This draft is the newest staging system based on the clinical practice and prognosis of a large series. China was the first to propose this draft for staging, and currently, similar drafts in many other countries exist. This draft of the staging system is suited for patients with oesophageal carcinoma who cannot undergo a surgical operation.

MATERIALS AND METHODS

Clinical data

Data were collected from 112 patients with oesophageal carcinoma admitted to the Department of Cardiothoracic Surgery of our hospital from January 2009 to June 2010. Patients underwent a barium meal, neck and chest CT, gastroscopic examination and biopsy, and abdominal ultrasound prior to operation. Epigastric CT, ECT or PET-CT was performed if necessary. No distant metastases were observed in any of the cases. All patients underwent surgical treatment, and intraoperative lymph node dissection was performed according to the AJCC criteria, i.e. no less than 12 lymph nodes were removed. Postoperative pathological examinations were performed in all the cases. Patient characteristics are listed in Table 1.

Table 1:

Patient characteristics

	Cases
Gender
Male	89
Female	23
Postoperative pathological type
Squamous cell carcinoma	101
Adenocarcinoma	11
Lesion location
Cervical portion	18
Upper thoracic segment	57
Lower thoracic segment	37
Degree of differentiation
Highly differentiated	47
Moderately differentiated	21
Poorly differentiated	30
Undifferentiated	14

Evaluation methodology

Pathological staging

The methods/criteria listed in the AJCC/UICC TNM Staging Standard for Esophageal Carcinoma, 7th Edition [1], were followed for the pathological staging in this study.

Clinical staging

The methods/criteria listed in the Clinical Staging Standard for Esophageal Carcinoma Treated with Non-Surgical Methods (Draft) [2] were followed for clinical staging in this study. Comparisons between the clinical staging and the pathological staging are described in Tables 2 and 3.

Table 2:

Comparison between the TNM staging system of the seventh edition and the clinical staging standard for oesophageal carcinoma treated with non-surgical methods

TNM staging system of the 7th edition (2009)						Clinical staging standard
T: primary tumour						T1  Lesion length in barium meal ≤3 cm and the diameter of oesophageal section with the largest lesion in CT ≤ 2cm, and no involvement of adjacent structures
Tx Primary tumour cannot be assessed						T2  Lesion length in barium meal >3–5 cm, and the diameter of oesophageal section with the largest lesion in CT >2–4 cm, and no involvement of adjacent structures
T0 No evidence of primary tumour						T3  Lesion length in barium meal >5–7 cm, and the diameter of oesophageal section with the largest lesion in CT >4 cm, and no involvement of adjacent structures
Tis Carcinoma in situ						T4  Lesion length in barium meal >7 cm, and the diameter of oesophageal section with the largest lesion in CT >4 cm, with involvement of adjacent structures (including trachea, bronchus, aorta, and pericardium)
T1a Tumour invades the lamina propria						Lymphadenectasis is the criterion for cancerous metastasis; the general standard is the short-axis diameter of lymph node ≥10 mm, the long-axis diameter of para-oesophageal lymph node, and lymph node in tracheoesophageal sulcus and pericardial lymph node ≥5 mm, and abdominal lymph node ≥5 mm
T1b Tumour invades the submucosa						N0 No enlargement of lymph node
T2 Tumour invades the muscularis propria						N1 Enlargement of lymph nodes in chest (para-oesophageal and mediastinum), carcinoma of inferior segment of oesophagus with left gastric lymphadenectasis, carcinoma of cervical portion of oesophagus with enlargement of supraclavicular lymph nodes
T3 Tumour invades the adventitia						N2 Carcinoma of the middle and lower thoracic oesophagus with enlargement of supraclavicular lymph nodes, carcinoma of any segment of oesophagus with enlargement of abdominal para-aortic lymph nodes
T4a Tumour invades the pleura, pericardium, diaphragm						M  Distant metastasis
T4b Tumour invades other adjacent structures						M0 No distant metastasis
N: Regional lymph nodes						M1 Distant metastasis
Nx Regional lymph nodes cannot be assessed
N1a 1–2 regional lymph nodes metastasis
N1b 3–5 regional lymph nodes metastasis
N2 6–9 regional lymph nodes metastasis
N3 ≥10 regional lymph nodes metastasis
M: Distant metastasis
Mx Distant metastasis cannot be assessed
M0 No distant metastasis
M1 Distant metastasis
H: Cell types
H1 Squamous cell carcinoma
H2 Adenocarcinoma
G: Degree of differentiation
Gx Cellular differentiation cannot be assessed
G1 Highly differentiated carcinoma
G2 Moderately differentiated carcinoma
G3 Poorly differentiated carcinoma
G4 Undifferentiated carcinoma
Subgroup	T	N	M	H	G	Clinical staging
0	is	0	0	–	1	Stage I: T1–2N0 M0
Ia	1	0	0	–	1	Stage II: T2N1M0, T3N0–1 M0
						Stage III: T4N0–2 M0
	1	0	0	2	2	Stage IV: T1–4N0–2M1
Ib	1	0	0	1	2
	1	0	0	–	3–4
	2	0	0	–	1
II	2	0	0	–	2–4
	3–4a	0	0	–	–
	1–2	1	0	–	–
IIa	3–4a	1a	0	–	–
IIb	3–4a	1b	0	–	–
	–	2	0	–	–
III	4b	–	–	–	–
	–	3	–	–	–
	–	–	1	–	–

Table 3:

Pathological and clinical staging

Staging standard	TNM staging
	I	II	III	IV
Pathological staging	46	51	15	0
Clinical staging	16	19	51	26
Staging standard	T staging
	T 1	T 2	T 3	T 4
Pathological staging	14	38	57	3
Clinical staging	11	49	37	15
Staging standard	N staging
	N0	N1(N1 + N2)		N2 (N3)
Pathological staging	55	51		6
Clinical staging	52	39		21

Statistical analysis

SPSS 13.0 was used for the data analysis, and the Kappa test was used to evaluate the consistency between the methods.

RESULTS

Based on the preoperative examination and clinical staging standard, consistency in the postoperative T staging, N staging and TNM was evaluated (Kappa values were 0.545, 0.615 and −0.090, respectively). The results are shown in Table 4.

Table 4:

Analysis of the degree of consistency between the TNM staging system of the 7th edition and clinical staging (the value of Kappa)

Staging	Pathological staging: clinical staging
TNM staging	−0.090
T staging	0.545
N staging	0.615

DISCUSSION

Recently, it was reported in a large series that the 5-year survival rate of oesophageal carcinoma was as high as 42% [3]. Its prognosis, however, was not good compared with other cancers in the alimentary tract. Numerous factors affecting the prognosis of the oesophageal carcinoma exist; of these, the lesion size and lymph node metastases are major influential factors [4]. Worldwide, literature reports have revealed that the 5-year survival rate of patients receiving concurrent chemoradiation was close to that of patients who underwent surgical treatment. Additionally, radiation therapy is quickly becoming a first choice in the treatment of oesophageal carcinoma. In the 6th edition of the TNM staging standard issued by the UICC, the N staging for the oesophageal carcinoma was only divided into N0 and N1 according to the presence of lymphatic metastasis [5]. In the 7th edition, the N staging was divided into N0, N1a, N1b, N2 and N3; however, the new TNM staging system can only be applied to cases of simple surgical resection [1].

In this study, the clinical T staging and the surgical–pathological T staging demonstrated consistency, but the degree of consistency was not sufficient (Kappa = 0.545 < 0.75). In the clinical staging, the variation in T1–T4 mainly involves the lesion size and length, as well as its involvement of adjacent structures; however, in the pathological staging, this variation mainly concerns the depth of infiltration. The heterogeneity of the proliferation and differentiation of the tumour cells and the irregularity of lesions are determined by the tumour's biological characteristics. Although, in this study, the consistency of these two systems was not very good, the results did demonstrate that the clinical staging could provide a more accurate assessment of the proliferation of tumour cells compared with the pathological staging.

The clinical N staging and the pathological N staging demonstrated consistency (P < 0.01) in this study, but the degree of consistency was only moderate (Kappa = 0.615 < 0.75). In retrospect, results from earlier studies showed poor consistency between the clinical N staging and the pathological N staging; however, the Kappa value of the clinical staging has increased significantly in the recent literature, mainly due to the number of lymph node dissections meeting the UICC staging standards (the number of lymph nodes dissected should be no less than 15, otherwise the staging is not reliable). Secondly, according to the evaluation standard for the surgical operation of an oesophageal carcinoma, the CT scan standard for the enlargement of lymph nodes was previously ≥1 cm; thus, it was of high specificity, but low sensitivity and accuracy [6]. In the new clinical staging system, the evaluation criteria for lymphatic metastases were the long diameter of the para-oesophageal lymph nodes, the lymph nodes in the tracheoesophageal sulcus and pericardial lymph nodes ≥5 mm and abdominal lymph nodes ≥5 mm; this has significantly increased the accuracy of the N staging. The evaluation criteria in the pathological N staging mainly relates to the number of lymph nodes, while the clinical N staging mainly involves the location of the primary lesion and metastatic lesions. The criteria of the two systems are different, and the evaluation of the clinical N staging includes supraclavicular and abdominal para-aortic lymph nodes, which are not included in the pathological staging system. In addition, the N staging in the pathological staging system is solely based on the number of lymphatic metastases. Therefore, the consistency of the N staging between these two systems is not satisfactory.

Compared with the TNM staging system, the degree of consistency between these two systems was poor (Kappa = −0.090). This was mainly due the tremendous difference between the evaluations of the M staging. In the pathological M staging, metastases to the supraclavicular and abdominal para-aortic lymph nodes are classified as distant metastases, i.e. M1; however, in the new clinical staging system, these are categorized as regional lymph nodes, and thus are categorized as the N staging. Metastasis of oesophageal carcinoma to the supraclavicular and abdominal para-aortic lymph nodes is of high incidence, and in this study, the incidence was 13/112 (11.6%). No patients recruited into this study had organ metastases, which also reduced the consistency of the clinical M staging and pathological M staging.

In summary, the T staging and N staging of the non-surgical staging system and postoperative pathological staging system demonstrated a certain amount of consistency, but the degree of consistency was not high. In addition, no consistency was observed in the TNM staging between the two systems. The clinical staging standard for the non-surgically treated oesophageal carcinoma has been adopted for a short period; however, a greater number of cases and more clinical practice are required to verify its validity. Its application in clinical practice will lay the foundation for the improvement of the non-surgical staging. Whether it can replace the pathological staging system and its significance of evaluating the prognosis remain to be seen.

Conflict of interest: none declared.