Mediastinal dissection for lung cancer is one of the controversial but a cross-cutting surgical management aspect of lung cancer. This presentation, which is based on the 9th ed. of TNM staging of lung cancer and associated IASCLC update on lymph node mapping, gives a good summary of the up-to-date approach to investigate the node status of lung ca. More importantly, it brings together the summary of the literature on the spearhead studies done to compare mediastinal lymph node dissection to systematic sampling.

1. Current Evidences on Mediastinal Lymph
Node Dissection for Lung Cancer
Ruhama Yoseph (CTF)
Moderator- Dr. Seyoum
May, 2025

2. introduction
TNM Staging and LN Mapping
Approaches of Invasive Staging
Options of mediastinal lymph node dissection
The evidences

3. Introduction
● The technique of mediastinal lymph node dissection (MLND) was first
described in detail in 1951, differentiating simple pneumonectomy from
radical pneumonectomy
● MLND differed in practice from mere inspection of unopened
mediastinum to radical lymphadenectomy
● MLND as a “standard” was followed by only 57.8%
● The effect of MLND was debated
● Later technique of mediastinal staging preceding surgical resection
introduced- Mediastinoscopy became a requirement for selected group
since 1993

4. Introduction
Naruke
LN map
introduced
1976
Martini
Modern MLND
technique
introduced
1995
1933
Graham
First successful
pneumonectomy
Allison
Radical
Pneumonectomy
1949
Cahan
Intrathoracic LN
dissection
1951

5. introduction
TNM Staging and LN
Mapping
Approaches of Invasive Staging
Options of mediastinal lymph node dissection
The evidences

6. LN Staging
The IASLC Ninth Ed cTNM Staging of Lung ca

7. LN Staging

8. History of the LN map…
The Naruke lymph node map for the staging of lung
cancers as recommended by the Japan Lung Cancer
Society, 1978
Interpretation of lymph node levels varied because of
the lack of precise anatomic definitions.
Confusion of stations 4 Vs 10, stations 1 through 4,
station 5 Vs 6, which were later modified

9. The Naruke LN map
History of the LN map…
Later modifications of station
10

10. The Mountain-Dresler modification of LN map (1997),
originally proposed by the American Thoracic Society, was
based on structures readily identified by CT scans
History of the LN map…

11. History of the LN map…
The IASLC ( International Association for the study of Lung
Cancer) LN map (2007) shows clear anatomic landmarks and
addresses controversial areas that had inter-observer variation for
labeling.
Controversial areas were:
● Right paratracheal and hilar lymph nodes
● Left inferior paratracheal and aortopulmonary lymph nodes
● The subcarinal and right hilar lymph nodes.

12. IASLC Nodal Chart

13. IASLC Nodal Chart

14. IASLC Nodal Chart

15. IASLC Nodal Chart
Intraoperative view of right
superior mediastinal and hilar
nodes

16. Intraoperative view left superior
mediastinal, aortopulmonary and
hilar nodes
IASLC Nodal Chart

17. IASLC Nodal Chart
Intraoperative view of right
subcarinal area
Lower limit is lower border of
bronchus intermedius

18. IASLC Nodal Chart

19. IASLC Nodal Chart

20. IASLC Nodal Chart

21. IASLC Nodal Chart

22. IASLC Nodal Chart

23. introduction
TNM Staging and LN Mapping
Approaches of Invasive
Staging
Options of mediastinal lymph node dissection
The evidences

24. Approach for C-Staging of Non-metastatic Lung Cancer
Positive lymph
nodes defined us
greater than 1 cm
in short axis

25. Approach for C-Staging of Non-metastatic Lung
Cancer
Who needs invasive LN staging?
● Patients who fulfill criteria based on CT-PET finding, OR
● Patients who are predicted to have N2/N3 disease based on prediction
models
Invasive staging preferentially beings with EBUS, EUS, EBUS/EUS

26. Invasive mediastinal staging
Lymph node sampling establishes nodal involvement for patients without evidence
of extrathoracic disease.
Based on CT-PET findings, it is recommended in the following scenarios:
● Patients without evidence of distant metastasis with evidence of mediastinal
and/or hilar node enlargement ( 1 cm),
≥ regardless of FDG uptake on PET
● Patients without distant metastases with normal-sized mediastinal and/or hilar
lymph nodes (<1 cm) on CT with FDG avidity on PET
● Patients with central tumor
● Patients with tumor size greater than 3 cm

27. Adenopathy in Lung cancer (HAL) prediction model:
A multivariable logistic regression model to predict the likelihood of N2/N3
disease based on age, the location and histology of the primary cancer, and the
N stage by CT and PET imaging
ESTS recommends that surgical candidates with a 10% or less predicted
chance of N2 disease may proceed directly to surgery without invasive
mediastinal staging
Patients with >10% risk of N2 disease should undergo invasive mediastinal
staging before surgery
Prediction models

28. EBUS and/or EUS
EBUS-TBNA
Needle deployed along the working channel of the flexible scope allows sampling
of paratracheal (2R/L, 4R/L), subcarinal (7), hilar (10R/L), interlobar (11R/L), and
interlobar (12R/L).
EUS-FNA
It allows for the sampling of some mediastinal lymph nodes accessible by EBUS
(2 L, 4 L, 7, 3p) as well as some which are not accessible via EBUS (stations 8, 9)

29. Mediastinoscopy
To be considered when EBUS is inconclusive and/or clinical suspicion remains
high despite negative EBUS/EUS
Allows sampling of stations 2R/L, 4R/L, 10 R/L and 7 via direct visualization or
leveraging of VAM.
Left Anterior Mediastinoscopy (Chamberlain procedure) is an option to
access aortopulmonary window & para-aortic LNs (5&6).

30. Options of mediastinal
lymph node dissection
introduction
TNM Staging and LN Mapping
Approaches of Invasive Staging
The evidences

31. Sampling- Process of harvesting grossly abnormal suspicious LN (keller 2000)
Later definition was extended to include normal looking LN.
Systematic Mediastinal LN Sampling (MLNS)- Routine biopsy of one or more
representative LN at predetermined stations/levels specified by author (Keller 2000)
According to Z0300 trial sampling of the following stations fulfilled criteria of MLNS
● stations 2R, 4R,7 and 10R on the right side
● stations 5, 6, 7 and 10L on the left side
Complete Mediastinal LN Dissection (CMLND)- routine removal of all LN containing
tissue within defined anatomic landmarks/levels indicated by investigators (Keller 2000)
Terminology of MLND

32. Sampling
A staging procedure for patients with proven NSCLC that were candidates for
invasive staging where they undergo rigorous sampling of normal looking
mediastinal and hilar LN (e.g The Z0300 trail)
In previous studies, LN that were grossly abnormal were taken ( e.g RCT by Wu et al.)
The methods:
● EBUS-TBNA/EUS-FNA
● Mediastinoscopy
● VATS/Open thoracotomy (frozen section examination at the time of surgery)

33. Systematic sampling (MLNS)
Systematic invasive sampling of mediastinal LN including all specified node
stations required based on location of the tumour (using EBUS/EUS,
Mediastinoscopy, VATS or thoracotomy)
Knowledge of distribution of nodal involvement in patients with N2 disease
can be helpful
E.g. Stations 5&6 for LUL tumours, 8&9 for lower lobe tumours

34. Complete MLND
By principle, all the mediastinal fatty tissue containing lymphatics should be
dissected and removed systematically.
For pathological staging (pTNM), a complete resection requires a minimum of
six stations including subcarinal station, two mediastinal nodes, and three
hilar or intrapulmonary nodes.
After removal, the different nodal stations will be put in different vials with
separate labeling.

35. Complete MLND…
For tumors on the right, all fatty lymphatic tissue harbouring:
● Paratracheal LNs (stations 2R & 4R) removed
● Prevascular (3a) and retrotracheal (3p) LN removed
● Subcarinal (station 7) removed
● Paraesophageal and inferior pulmonary ligament LN (station 8R & 9R) removed
● N1 zone LN (stations 10R to 14R) removed along or separate from specimen

36. For tumors on the left, all fatty lymphatic tissue harbouring:
● Aortopulmonary window (station 5) & Para Aortic (station 6) LN removed
● Subcarinal (station 7) removed
● Paraesophageal and inferior pulmonary ligament LN (station 8L & 9L) removed
● N1 zone LN (stations 10L to 14L) removed along or separate from specimen
Complete MLND…

37. Complete MLND- Right Thoracotomy
Paratracheal LN (2R and 4R)
Accessed by retracting lung down &
opening pleura above the azygos vein,
developing anterior and posterior pleural
flaps
The upper boundary of dissection is the
right subclavian artery takeoff where the
recurrent laryngeal nerve is also located.
Vessels secured.

38. Subcarinal LN (station 7)
Approached by retracing the lung anteriorly,
opening pleura between azygos and hilum.
Nodal packet lying between carina/right
bronchus superiorly and inferior pulmonary
vein inferiorly swept off proximally along
the right main stem bronchus.
Vessels secured.
Complete MLND- Right Thoracotomy…

39. Complete MLND- Right Thoracotomy…
Inferior mediastinal LN (8R & 9R)
Tension on the RLL allows the opening of
the inferior pulmonary ligament with its
anterior and posterior leaves exposing
station 9 nodes.
The station 8 nodes are located in the
paraesophageal region which will become
evident upon exposure of the esophagus.

40. Hilar LN (10R)
Accessed by opening the (?visceral) pleura
anteriorly along the superior hilum and they
are located along the distal part of bronchus
posterior to the RPA and inferior to azygos.
Interlobar LN (11R) or “sump” nodes
located within bifurcation of upper
bronchus and bronchus intermedius.
Lobar LN (12R) nodes exposed when
bronchus is transected and the rest
Peripheral LN (13R & 14R) in general
included within the lobectomy specimen
Complete MLND- Right Thoracotomy…

41. Complete MLND- Left Thoracotomy
Aortic LN (5 & 6)
To approach LUL retracted inferiorly and
mediastinal pleura opened over the LPA
between phrenic and vagus nerves and
flaps developed towards aortic arch.
Ofnote, station 6 is situated in the
prevascular space.
Station 5 nodes are found more
posteriorly, lateral to ligamentum
arteriosum( medial to it is left paratracheal
or 4L).

42. Complete MLND- Left Thoracotomy…
Subcarinal LN (station 7)
Lung retracted anteriorly and pleura
opened over the groove anterior to
descending thoracic aorta retracting it
posteriorly. The left main bronchus
exposed and LN packet inferior to the
carina grasped.

43. Complete MLND- Left Thoracotomy…
Inferior mediastinal LN (8L & 9L)
Approach same as the right side
Hilar LN (10L)
It is found inferior to the LPA and posterior
to the superior pulmonary vein at the distal
left mainstem bronchus

44. introduction
TNM Staging and LN Mapping
Approaches of Invasive Staging
Options of mediastinal lymph node dissection
The evidences

45. Izbicki et al.
(169 patients-Stage I, II, IIIA NSCLC)
✖
● EFfectiveness of radical systematic mediastinal
lymphadenectomy in patients with resectable non-small cell
lung cancer: Results of a prospective randomized controlled
trial
Studies addressing the survival benefit of complete MLND have been
inconclusive with only one out of three previous randomized prospective trials
reporting a survival advantage ( in pre-mediastinoscope era).
Proponents argue that MLND by removing occult N2 disease, would lower
recurrence and increase survival. However, two-thirds of patients with N2
disease develop distant metastases as their first site of recurrence.
Wu et al.
(532 patients- stage I, II, IIIA NSCLC)
✅ ● A randomized trial of systematic nodal dissection in
resectable non-small cell lung cancer
Sugi et al.
(115 patients-stage I, small
peripheral NSCLC)
✖
● Systematic lymph node dissection for clinically
diagnosed peripheral non-small cell lung cancer less
than 2 cm in diameter.

46. Manser 2005
A Meta-analysis
A meta-analysis of relevant RCTs on this topic ( Sugi 1998,
Izbicki 1998, Wu 2002)
Conclusion- overall survival was superior (pooled analysis) in
patients with resectable stage I to IIIA NSCLC who underwent
resection and CMLND compared with those undergoing
resection and MLNS (hazard ratio 0.63, 95% CI 0.51 to 0.78, P
0.0001) and there was no statistically significant
≤
heterogeneity.
There was a significant reduction in any cancer recurrence
(local or distant) in the CMLND group (RR 0.79, 95% CI 0.66 to
0.95, P = 0.01) and there was no significant statistical
heterogeneity (P = 0.64).
Limitation- small number of participants and methodological
weakness of primary studies

47. Keller 2000
(Part of Intergroup Trial 0115)
Non-randomized prospective trial of 373 patients, patients
with completely resected stages II and IIIa NSCLC,median
survival was 57.5 months for those patients who had
undergone complete MLND (186) and 29.2 months for
those patients who had SS (p 0.004). However, the DFS
advantage was limited to patients with right lung tumors
(66.4 months vs 24.5 months, p < 0.001).
Conclusion- SS was as efficacious as complete MLND in
staging patients with NSCLC. However, complete MLND
identified significantly more levels of N2 disease. CMLND
was associated with improved survival with right NSCLC when
compared with SS.
Limitation- non-randomization, retrospective and relatively
small number of study units, higher stage of disease

48. A series of 100 patients with T1-3 N0-1 (radiologically)
NSCLC disease grouped into CMLND or MLNS groups (50
each) based on preference of surgeon
Significantly longer disease-free survival after MLND
compared with MLNS(60 months vs. 45 months, p < 0.03) in
patients with stage I and a significantly higher local
recurrence rate after MLNS (compared with CMLND 13% vs.
45%, p = 0.02) in patients with stage I disease.
Conclusion- There was no difference observed in overall
survival & DFS except in those with Stage I disease.
Increased recurrence after MLNS observed.
Limitation- non-randomized and retrospective, small sample
size
Lardinois 2005

49. The ACOSOG Z0300 Trial
A multi-institutional prospective RCT conducted 1111
patients (1023 eligible) with N0 or N1 early NSCLC that
were randomized into CMLND and MLNS arm revealed
that there was no statistically significant difference in
median survival (P=0.25), 5-year DFS (P=0.92) and
recurrence (local P=0.51, regional P=0.10, distant
P=0.76)
Conclusion- If systematic through pre-resection
sampling of mediastinal & hilar LN is negative, CMLND
doesn’t improve survival and recurrence rates in
patients with early stage NSCLC.
CMLND didn’t increase morbidity and mortality.
*Not applicable for patients: staged radiologically
only and/or tumours of higher stage.

50. A retrospective study of 1,358 patients clinically staged as N0 who
underwent curative resections and CMLND (not MLNS) was compared
to N2 disease reported by the Society of Thoracic Surgeons (STS)
database( considered to represent MLNS).
In patients who underwent segmentectomy, N2 disease was detected
more frequently(13% vs 5.3%, P<0.001) in patients who had
preoperative clinical N0 disease (EBUS,EUS, Mediastinoscopy) as
compared to the controls.
Conclusion- When CMLND is performed in patients during
pulmonary resection who are clinically node negative, more patients
are pathologically staged with N2 disease.
Limitation- Retrospective, non-randomized, assumption may be
wrong, survival not studied
Cerfolio 2012

51. Conclusion
Meta-analysis of studies done in pre-mediastinoscope era revealed survival advantage of
complete MLND over MLNS which may be relevant for application in the Ethiopian setup.
Nevertheless, the most recent Z0030 trial ,which has superior methodology in terms of
randomization, standardization and sample size, didn’t prove survival advantage of
complete MLND over MLNS even though the context of the study differs largely from the
practice in an average setup.
MLND is safe and superior in detecting clinically “occult” N2 disease.
Recommendation- further studies (trials) on survival advantages of CMLND Vs MLNS in
resource limited setup

52. THANK YOU!

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References

54. References
The Radiology Assistant