What is the best way to treat the axilla?

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What is the best way to treat the axilla?
19th century
21st century
Jayant S Vaidya MBBS MS DNB FRCSGlag PhD FRCS(Gen
Surg)
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For

• Axillary Sampling with a choice of flavours
• Clearance
• 4-node Sample
• Blue dye guided Sample
• Sentinel Node biopsy
• for
• A CHOICE
• of axillary sampling procedures

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Once upon a time..
Tata Memorial Cancer Centre
Axillary Clearance
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Middlesex Hospital, University College London
Axillary Clearance
Sentinel Node Biopsy
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Ninewells Hospital, University of Dundee
Axillary Clearance
Sunshine in Oct
Axillary Sample
best of both worlds
Sentinel Node Biopsy
Snowshine in Feb
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False negative rateThe chance of missing a
positive axilla
Could cause harm by Axillary relapse Missed
opportunity to institute systemic adjuvant therapy
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How Much?
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Mathematical Model
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Mathematical Model
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The mathematical model- the known facts
(NSABP B-32) trial False negative rate
(FNR) SEER dataset Estimated node positivity
(ENP) www.adjuvantonline.com Benefit from
chemotherapy in ER negative women This
would be similar to additional benefit of
chemotherapy in ER positive women on top of
hormone therapy
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The mathematical model- the known facts
NSABP B-04 (Fisher, 2002) 50 of involved
nodes cause local recurrence Overview (Peto
R, 2004) 20 of local recurrence translates
into mortality (for example, if
LR increases by 10 the mortality increases
by 2) Thus, if 10 of patients have untreated
axillary disease, 5 will have local
recurrence 1 more will die as a consequence.
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Mathematical Model

• Age 60 years
• Grade 1
• 0.5cm
• ER negative
• Estimated Node Positivity
• (ENP) 10

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• The 10-Year mortality risk
• Node negative women
• 3
• 1 to 3 - Node positive women
• 13

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• The Benefit from adjuvant chemotherapy
• (reduction in 10 year mortality)
• If Node negative
• (adjuvantonline.com)
• 0.8
• If (1 to 3) Node positive
• (adjuvantonline.com)
• 3.4

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• Difference in benefit if NN vs. if NP
• is
• 3.4 minus 0.8 2.6

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• Let us assume the False Negative Rate of SNB is
• 9.7

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Mathematical Model

• Actual (chance of )False Negative axilla in this
  patient undergoing SNB is
• AFN FNR x ENP
• e.g., if FNR 9.7 and ENP is 10
• AFN 1

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Mathematical Model

• Actual chance of missing a positive axilla in
  this patient is (AFNENP x FNR)
• 1
• Increased mortality due to axillary recurrence
• 1/10th of 1
• 0.1

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Mathematical Model

• Actual chance of missing a positive axilla in
  this patient is (AFNENP x FNR)
• 1
• Increased mortality due to no chemotherapy
• 2.4 times D (diff. in benefit in NN and NP)
• 1 x 2.6
• 0.02

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• Unsuspected harm in this SNB-negative woman
  (60yrs, 1.5cm, Grade I, ER-ve)
• because of omitting chemotherapy on assumption
  that she is node negative
• Increased Mortality due to axillary recurrence
• Increased mortality due to no chemotherapy
• 0.1 0.02
• 0.12

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• Tweak

Increase False Negative Rate to
20
100
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• Unsuspected harm in this SNB-negative woman
  (60yrs, 0.5cm, Grade i, ER-ve)
• because of omitting chemotherapy on assumption
  that she is node negative
• (FNR20)
• Increased Mortality due to axillary recurrence
• Increased mortality due to no chemotherapy
• 0.2 0.05
• 0.25

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• Unsuspected harm in this SNB-negative woman
  (60yrs, 0.5cm, Grade i, ER-ve)
• because of omitting chemotherapy on assumption
  that she is node negative
• (FNR100)
• Increased Mortality due to axillary recurrence
• Increased mortality due to no chemotherapy
• 1 0.26
• 1.26

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False negative rate does not matter
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But
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• More Tweaks

Increase tumour size and grade
Size 2cm
Grade 2
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• Unsuspected harm in this SNB-negative woman
  (60yrs, 2 cm, Grade ii, ER-ve)
• because of omitting chemotherapy on assumption
  that she is node negative
• (FNR9.7)
• Increased Mortality due to axillary recurrence
• Increased mortality due to no chemotherapy
• 0.29 0.11
• 0.4

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• Unsuspected harm in this SNB-negative woman
  (60yrs, 2 cm, Grade ii, ER-ve)
• because of omitting chemotherapy on assumption
  that she is node negative
• (FNR20)
• Increased Mortality due to axillary recurrence
• Increased mortality due to no chemotherapy
• 0.6 0.22
• 0.82

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• Unsuspected harm in this SNB-negative woman
  (60yrs, 1.5cm, Grade I, ER-ve)
• because of omitting chemotherapy on assumption
  that she is node negative
• (FNR100)
• Increased Mortality due to axillary recurrence
• Increased mortality due to no chemotherapy
• 3 1.11
• 4.11

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• Tweaks

Increase tumour size, grade and reduce age
Size 2cm
Grade 3
Age 40
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• Unsuspected harm in this SNB-negative woman
  (40yrs, 2 cm, Grade iii, ER-ve)
• because of omitting chemotherapy on assumption
  that she is node negative
• (FNR9.7)
• Increased Mortality due to axillary recurrence
• Increased mortality due to no chemotherapy
• 0.34 0.22
• 0.56

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• Unsuspected harm in this SNB-negative woman
  (40yrs, 2 cm, Grade iii, ER-ve)
• because of omitting chemotherapy on assumption
  that she is node negative
• (FNR9.7)
• Increased Mortality due to axillary recurrence
• Increased mortality due to no chemotherapy
• 0.34 0.22
• 0.56

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• Unsuspected harm in this SNB-negative woman
  (40yrs, 2 cm, Grade iii, ER-ve)
• because of omitting chemotherapy on assumption
  that she is node negative
• (FNR20)
• Increased Mortality due to axillary recurrence
• Increased mortality due to no chemotherapy
• 0.7 0.46
• 1.16

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• Unsuspected harm in this SNB-negative woman
  (60yrs, 1.5cm, Grade I, ER-ve)
• because of omitting chemotherapy on assumption
  that she is node negative
• (FNR100)
• Increased Mortality due to axillary recurrence
• Increased mortality due to no chemotherapy
• 3.5 2.31
• 5.81

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• We need to inform our patients and take a shared
  decision about using Sentinel Node Biopsy?

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NSABP B-32 Smoothed Technical Failure Rates
15
10
p lt 0.0001
Percentage Technical Failure
5
0
0
50
100
150
Surgeon Case Number
NSABP B-32 Smoothed False Negative Rates
60
p 0.30
40
Percentage False Negative
20
0
0
50
100
150
Surgeon Case Number
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• We need to accept that this 10 false negative
  rate is not a correctable technical error
• It is an indicator of the biological behaviour
  of breast cancer

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• barking dogs do not bite
• but
• the dog doesnt know that

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• SNB is appealing because it is precise and
  logical
• But
• breast cancer doesnt know the rules!

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• In 10 of cases tumour skips the sentinel lymph
  node

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Is there an alternative?
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There is an alternative
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Replace dogma with informed choice
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Edinburgh Studies
Prof Bob Steele, Mr Udi Chetty, Sir Patrick
Forrest and colleagues Mastectomy (417) Breast
conservation (466)
4- node sample
RANDOMISATION
Axillary clearance
Outcome- local relapse, survival and morbidity
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Technical Success

• Sample Clearance
• (202) (199)
• Mean Number 4.8 20.6
• Positive 85(42) 80 (40)
• Failure 1 0

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False negative rate
In 135 patients, randomisation was done after
sampling N Positive Additional
Positive Sample only 68 26 (38) - Sample Cl
earance 67 26 (39) 0
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Overall Survival
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Axillary Recurrence
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Arm Oedema
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4-node sample the Edinburgh technique Near 100
detection rate Near 0 false negative rate Low
morbidity Survival and local relapse equivalent
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• 4-node sample - Other benefits
• No need of costly equipment
• No need of Nuclear medicine and ARSAC
• No need of radiation protection
• Needs proper surgical training

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Study of biology of

• Biological tissues are NOT contaminated with
  radiation
• So can be stored in tissue bank for further study
  e.g., gene microarray analysis.

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Applying the Mathematical model to 4 node sampl e

• FNR 0
• Effect of mortality 0
• Effect of local recurrence 0

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Node positivity in trials of SNB

• 26
• On average,
• 1 in 4 patients have a second operation

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Patient Choice

• A. ¾ chance of an unnecessary axillary procedure,
  but the full treatment is completed in one
  operation (AC)
• B. ¼ chance of 2nd operation 1/10 chance of a
  missed positive node (SNB)
• C. ¼ chance of a 2nd procedure 0 chance of a
  missed positive node (AS)

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What is the right way?

• INFORMED CHOICE AND PATIENT SELECTION
• Those with high risk of nodal metastasis
  Axillary clearance
• Those with medium risk of nodal metastasis
  Axillary sample
• Those with low risk of nodal metastasis
• Sentinel node biopsy (dont bother about FNR)

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REMEMBER WHEN YOU VOTE

• If you Vote for the action then you are voting
  for a choice surgeon choice and patient choice-
  in different ways of sampling the axilla
  Clearance-Sample-SNB
• If you Vote against the action then you are
  voting against such an informed and wise choice
  and NOT for Sentinel node biopsy.

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Remember

• VOTING AGAINST this action is NOT the same as to
  VOTING FOR SNB
• So if you believe that SNB
• is
• A right way
• then you should vote FOR the action

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Vote for choice
If you wish to just replace the dogma of
Axillary clearance to the dogma of Sentinel node
biopsy Vote against the action

• If you believe that Surgeons and Patients should
  be allowed to make an informed choice
• Vote for
• the action

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