Lung Cancer 45 Suppl. 2 (2004) S85–S87

www.elsevier.com/locate/lungcan

Mediastinal staging (take home messages)

Bernward Passlick

Dept. of Thoracic Surgery, University Hospital Freiburg, Hugstetter Straße 55,

D-79106 Freiburg, Germany

KEYWORDS

Staging;

lung cancer;

mediastinoscopy;

PET

Summary Mediastinal lymph-node involvement is still the major prognostic

factor in NSCLC. Currently, cervical mediastinoscopy is the gold standard

of mediastinal lymph-node staging. However, less invasive methods such

as transbronchial or transoesophageal FNA are becoming more popular and

might replace or adjunct mediastinoscopy under certain circumstances. It

has been clearly shown that FDG PET is more accurate than CT for the

detection of mediastinal lymph-node metastases. However, a positive finding

on the PET scan implies that these lymph nodes have to examined by

invasive methods (e.g. mediastinoscopy). It has been demonstrated that PET

might be useful in order to detect non-symptomatic distant metastases. The

method of pathological analysis of the lymph nodes is critical for the correct

determination of the N stage.

© 2004 Elsevier Science Ltd.

1. Introduction

Non-small cell lung cancer (NSCLC) metasta-

sizes usually first to the hilar and mediastinal

lymph nodes. During the later course of the disease

distant metastases are very common.

Since the treatment plan and the prognosis are

determined by the extent of the disease at the

time of diagnosis nearly every patient with a newly

diagnosed NSCLC had to undergo certain staging

procedures. In this context the accurate staging

of the mediastinal lymph nodes is of major im-

portance. While contralateral lymph-node involve-

ment generally implies irresectability, the optimal

approach to patients with ipsilateral lymph-node

metastases is the subject of debate (neoadjuvant

therapy?, resection followed by radiotherapy?).

* Prof. Dr. B. Passlick. Arztlicher Direktor, Abteilung fur

Thoraxchirurgie, Universitatsklinikum Freiburg, Hugstetter

Straße 55, D-79106 Freiburg, Germany

Tel.: +49-(761)-270-2457; fax: +49-(761)-270-2499.

E-mail: passlick@ch11.ukl.uni-freiburg.de

Furthermore, it has been shown that within

the group of patients with N2 involvement the

prognoses are extremely heterogeneous: Patients

with preoperative confirmed N2 disease showed a

5-year survival of only 8–10%, while patients with

only intraoperatively diagnosed N2 disease at a

single lymph-node level have survival probability of

about 34% 5 years after surgery.

Therefore, the extent of mediastinal lymph-node

involvement must be determined as precisely as

possible in order to define an optimal treatment ap-

proach for the individual patient.

2. N status and prognosis

In spite of numerous markers and molecular

prognostic factors, the extent of mediastinal lymph-

node involvement (N–status) remains the most

important parameter to determine the clinical

outcome in patients without distant metastases.

Not only the different pN stages (pN0–pN3) are

0169-5002/$ – see front matter © 2004 Published by Elsevier Ireland Ltd.doi:10.1016/j.lungcan.2004.07.000

S86 B. Passlick

of prognostic significance, but also the extent of

lymph-node involvement within a given pN stage.

For example, patients with N1 disease limited to

the intrapulmonary lymph-node levels have a better

outcome than patients with involvement of the hilar

lymph-node levels.

Furthermore it has to be noted that the size

of a lymph node as determined by CT scan is a

poor indicator of malignancy: While 25% of the

lymph nodes less than 1 cm in diameter are tumour-

involved, 23% of lymph nodes larger than 2 cm are

benign.

3. Mediastinoscopy and intraoperative

staging

With respect to mediastinal lymph-node staging,

cervical mediastinoscopy is reported to have a

sensitivity of 72–89%. This observation is mainly

due to the fact that some lymph-node levels

(# 8, 9, 5, 6) are not accessible by the standard

cervical approach. Video-mediastinoscopy allows

the procedure to be even more standardised,

and preliminary data suggest that the sensitivity

might be improved in comparison with conventional

mediastinoscopy. Since histopathological analysis of

surgical biopsies remains the gold standard for the

detection of tumour involvement of lymph nodes or

other tissues, surgical staging approaches, including

mediastinoscopy, have a per se specificity of 100%.

The morbidity and mortality of cervical medi-

astinoscopy is only minimal in experienced centers.

In series with more than 1000 patients the mortality

was almost 0% and morbidity varied between

0.5–1%, consisting mostly of arrhythmias. However,

in smaller series the complication rate is reported

to be higher. Cervical mediastinoscopy can be

performed also as an outpatient procedure.

Currently, almost all national and international

associations (American Thoracic Society, European

Respiratory Society, German Society for Pneu-

monology) recommend a staging mediastinoscopy

only in patients with lymph nodes of more than

1 cm in short-axis diameter on the pretherapeutic

CT scan. This includes also the recent recommen-

dations of the British Thoracic Society.

4. Mediastinal staging – the role of

endobronchial and endo-oesophageal

sonographic guided needle aspiration

It has been demonstrated that transbronchial

needle aspiration (TBNA) with or without ultrasound

guidance is an elegant technique to get cytologic

information from peribronchial lymph nodes. How-

ever, the method requires a lot of experience

and until now has been established only in a

few centers. Oesophageal ultrasound (EUS) with

FNA is a minimally invasive technique to stage

paraoesophageal lymph nodes. Therefore, it is

extremely useful in patients in whom the analysis

of paraoesophageal lymph nodes is critical for the

therapeutic plan. EUS–FNA can access lymph nodes

that are not reachable by cervical mediastinoscopy.

The complication rate is reported to be negligible.

5. FDG PET: advantages for staging the

mediastinum?

It has been shown clearly that FDG PET is

more accurate than CT for the detection of

mediastinal lymph-node metastases. Dual-modality

PET–CT scanners might be even more exact in

staging the mediastinum. However, currently only

a few studies are available.

In view of the high negative-predictive value of

PET a patient with a negative PET scan of the

mediastinum can proceed directly to thoracotomy.

In contrast, a positive finding on the PET scan

implies that these lymph nodes have to examined

by invasive methods (e.g. mediastinoscopy). Until

now a systemic comparison between PET and FNA

procedures (transbronchial or transoesophageal)

have not been performed.

6. Value of FDG PET in the management

of NSCLC

PET might be useful for detecting non-symptomatic

distant metastases. Some studies have demon-

strated that this might be the case in 3–24% of

the patients. However, the brain as a frequent site

of distant metastases in NSCLC cannot be assessed

by PET scanning, and positive findings have to

be confirmed by other methods or by biopsy. The

problem of costs and efforts to rule out false-

positive findings has not been addressed so far.

The authors of the so-called “PLUS” study

concluded that routine PET scanning might be useful

to reduce the number of “futile” thoracotomies

by 20%. However, the study has a number

of methodological problems, including a poor

staging in the control group with only a few

mediastinoscopies and a modern CT scan in only

55% of the patients. Furthermore the definition of

“futile thoracotomies” is the subject of debate.

Repeated PET scanning seems to be very

promising for the evaluation of the therapeutic

efficacy of chemotherapy or radiochemotherapy.

Mediastinal staging (take home messages) S87

7. Histopathologic evaluation of

the mediastinal lymph nodes in

lung cancer

It has been demonstrated that the current methods

for the pathological analysis of the mediastinal

lymph nodes are not standardised. However, some

parameters including the staining methods and the

number of slices per lymph node are important

for the correct determination of the pN status.

Therefore, in order to improve the comparability

of histopathological reports a widely accepted

consensus should be implemented.

8. Conclusion

Currently, cervical mediastinoscopy is the gold stan-

dard of mediastinal lymph-node staging. However,

less invasive methods such as transbronchial or tran-

soesophageal FNA are becoming more popular and

might replace or adjunct mediastinoscopy under

certain circumstances. It has been shown clearly

that FDG PET is more accurate than CT for the

detection of mediastinal lymph-node metastases.

However, a positive finding on the PET scan implies

that these lymph nodes have to examined by

invasive methods (e.g. mediastinoscopy).