Staging of lung cancer: endoscopic examinations

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Staging of lung cancerendoscopic examinations

• Kurt TOURNOY
• Ghent University Hospital - BE

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Staging

• Staging of NSCLC determines
• Treatment options
• Prognosis
• cTNM should be available before anti-cancer
  therapy is administered
• cT mainly by CT and bronchoscopy (no major
  changes past 5 y)
• cM mainly by CT, PET/CT, bone scan (no major
  changes past 5y)
• cN new tools challenge the current standard of
  care

Invasive Staging The Guidelines Chest 2003
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Mediastinal Staging

• In NSCLC, mediastinal staging should be performed
  whenever
• Enlarged LN are present (CT scan)
• FDG avidity is documented in a mediastinal LN
• Specific situations representing a  higher than
  expected risk  for LN or mediastinal invasion
• Regardless the technique, mediastinal staging
  should report on
• Mediastinal LN invasion (N2/3)
• Direct mediastinal Tumor invasion (T3/4)
• Imaging techniques (CT and integrated FDG-PET/CT)
  are contributive, but the current consensus is
  that neither is accurate enough to rule in/out
  locally advanced disease

Lung Cancer, Lippincot Williams Wilkins,
2005 Gould, M.K. Ann.Int.Medicine 2003
Tournoy, K.G. Thorax 2007
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Current standard of care

• Cervical mediastinoscopy
• Extended mediastinoscopy
• Parasternal medastinoscopy
• Mediastinotomy
• VATS

Invasive Staging The Guidelines Chest,
2003 Annema,J. JAMA 2005
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The challenge linear endoscopic ultrasonography
X


target
target
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Linear Endoscopic Ultrasound Equipment

• EBUS-TBNA
• bronchoscope (Ø 6 mm - L 60 cm)
• ultrasound-head (4 x 9 mm)
• real time controlled puncture
• Endoscopic landmarks (stereo view)

• EUS-FNA
• gastroscope (Ø 12 mm - L 160 cm)
• ultrasound-head (12 x 13 mm)
• real time controlled puncture
• Ultrasound landmarks

Real time guided puncture (what you see is what
you get) is the main reason why techniques such
as (blind) TBNA and radial EBUS followed by
(blind) TBNA did not become common practice
(Holty, Thorax 2005)
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EUS-FNA and EBUS-TBNA are compementary
EUS 2R/2L/4L/5/7/8/9 EBUS 2R/2L/4R/4L/7 Blind
spots EUS 2R,4R, Hilar LN Blind spots EBUS 5,8,9
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OUTLINE

• RESULTS what is (not) known about EUS-FNA and
  EBUS-TBNA
• IMPACT ON PATIENT MANAGEMENT
• IMPACT ON STAGING ALGORITHMS

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EBUS-TBNA
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EBUS-TBNA the studies

• Linear EBUS-TBNA and mediastinal T(4)-staging
  no data
• Linear EBUS-TBNA and N-staging 5 papers
• Yasufuku Chest 2004 ? 70 ptn sens 97
• Yasufuku Lung Cancer 2005 ? 105 ptn sens 95
• Yasufuku Chest 2006 ? 102 ptn sens 92 (PET )
• Herth Thorax 2006 ? 502 ptn sens 94
• Herth ERJ 2006 ? 100 ptn sens 92 (LN lt1cm)

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EBUS-TBNA the studies

• Prospective study (Yasufuku Chest 2006)
• 102 lung cancer pts CT/PET-CT and EBUS-TBNA
• N2/3 prevalence 26

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EBUS-TBNA impact

• Prospective study (Yasufuku Lung Cancer 2005)
• ? in a study of 108 pts, EBUS detected 64 / 68
  pts with N2/3 (sens 94)
• avoidance of 29 MS, 8 TT, 4 VATS and 9 CT guided
  PCNB 50
• ? this means that EBUS impacts the staging trajet
  in 50/108 pts (46)

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EUS-FNA and T-diagnosis / stage
T4 or not is EUS reliable ?
Studies 1/ radial EUS sens 83 (10/12 pT4
pts), spec 98 2/ linear EUS sens 44 (7/17
pT4 pts), spec 100 ? Message no solid data,
cautious interpretation
Schroder,C. Chest 2005 Annema,J. JAMA 2005
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EUS-FNA and N-stage
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EUS-FNA and N-stage

• Several series have been published, together
  including gt500 pts
• Eloubeidi, Ann Thorac Surg 2005 (104 pts, LNgt1cm)
• Annema, JAMA 2005 (107 pts, LNgt1cm)
• Annema, JCO. 2005 (242 pts, LNgt1cm)
• Tournoy, Chest 2005 (67 pts, LNgt1cm)
• Le Blanc, AJRCCM 2005 (62 pts, LNlt1cm)
• Wallace, Ann Thorac Surg. (69 pts, LNlt1cm)

Prev 70 Sens gt90-95 Spec 100
Prev 34-36 Sens 36-61 Spec 100
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PET-CT for US-guided targeting of mediastinal LN
?

Idea FDG-PET/CT high NPV (sens
gt90) EUS-FNA high PPV (spec 100) Why not
combining the best of these two ? Kramer (Thorax
2004) analysis in PET mediastinal LN

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EUS-FNA impact
If EUS-FNA is available what is the clinical
impact ? - prospective study, 242 pts
(LNgt1cm), prevalence N2-3 71 - prevention of
surgical procedure in 169/242 pts N2
49 N3 3 T4N2 5 T4N0 4 SCLC
8 70 - cost reduction (less
hospitalisation - 40) Annema, JCO
2005 Kramer, Thorax 2004
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EUS-FNA and re-staging
Varadarajulu, S. (Respiration 2006) pilot
study 14 IIIA NSCLC treated with Chemo-radiation
therapy 8 had residual N disease, 6 were
tumor free. EUS detected 7/8 with residual
disease. Accuracy 86 Annema, J. (Lung
Cancer 2003) pilot study 18 IIIA NSCLC treated
with chemotherapy 12 had residual N disease,
and EUS detected 9/12 Accuracy 83
Message - no solid data on restaging -
role of re-mediastinoscopy ? (De Leyn, JCO 2006
243333) - role of PET/CT ?
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EUS-FNA is a (r)evolution !

• Safe
• Minimally invasive
• Ambulatory
• Reduces hospitalisation and costs
• Is very sensitive to detect malignant LN and is
  good for demonstrating immediate
  irresectability (N2/N3 detection)
• Has an impact on pt management (avoids surgery
  in 50-70)

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EUS and mediastinoscopy ?

• Is there an added value of mediastinoscopy
  to EUS-Fna or vice versa?
• Annema, JAMA 2005 EUS followed by mediast in
  NSCLC
• 100 ptn with N2/3 prevalence of 36
• EUS-FNA positive in 22/29 (reachable LN) ? sens
  72
• Mediastinoscopy positive in 19/29 (reachable
  LN) ? sens 66
• EUS-FNA followed by mediastinoscopy positive in
  31/36 ? sens 86
• ? Eloubeidi, Ann.Thorac.Surg. 2005 Mediast
  followed by EUS in NSCLC
• 35 pts suspect for N2/N3 but negative
  mediastinoscopy underwent EUS-FNA
• 13/35 pts had malignant N2/3 disease (37.1)

? Neither is perfect
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A revolution ? Or not ?

• Regardless the technique, mediastinal staging
  should report on
• - Mediastinal LN invasion (N2/3)
• - Direct mediastinal Tumor invasion (T3/4)
• Which are the problems EUS and/or EBUS are faced
  with?
• 1/ All data are subjected to selection-bias
  (analysis in enriched populations with a
  prevalence of malignant LN 50-85) ? lack of
  randomized trials
• 2/ Neither EUS, nor EBUS allow a complete (L/R)
  pathology LN mapping
• 3/ EUS and EBUS have their own blind spots and
  thus potentially miss N3
• 4/ The demonstration of single level N2 might
  be to minimalistic
• 5/ The NPV of EUS and EBUS remains lt95 ?
  confirmation necessary
• 6/ The data about mediastinal (T4) invasion are
  premature, for EUS and EBUS
• 7/ There is a current lack of training
  facilities ? results transferable to not-expert
  centers ?

Sakao,Y. ATS. 2006
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But how should I stage anno 2007 ?

• CT FDG-PET/CT
  mediastinoscopy EUS-FNA
  EBUS-TBNA
• TAKE HOME
• whenever mediastinal staging of lung cancer is
  needed, consider EUS-FNA or EBUS-TBNA because
  these techniques can show immediate
  irresectability in a substantial amount of
  patients.
• the gaps (single level staging, no firm data on
  T4, insufficient NPV) should however always be
  kept in mind and will guide new clinical trials
  in 2007