What is the best way to treat the axilla?

What is the best way to treat the axilla?

Jayant S VaidyaMBBS MS DNB FRCSGlag PhD FRCS(Gen Surg)

19th century19th century 21st century21st century

ForAxillary Sampling …with a choice of

flavours… Clearance

4-node SampleBlue dye guided Sample

Sentinel Node biopsy

for…A CHOICE

of axillary sampling procedures

Tata Memorial Cancer Centre

Axillary Clearance

Once upon a time…..

Middlesex Hospital, University College LondonMiddlesex Hospital, University College London

Sentinel Node Biopsy

Axillary Clearance

Ninewells Hospital, University of Dundee

Axillary Clearance

Sunshine in Oct

Snowshine in Feb

Axillary Sample –

Sentinel Node Biopsy

best of both worlds

False negative rateThe chance of missing a

positive axillaCould cause harm by

Axillary relapse

Missed opportunity to institute systemic adjuvant therapy

How Much?

MathematicalModel

MathematicalModel

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 womenThis would be similar to additional benefit of chemotherapy in ER positive women on top of hormone therapy

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 recurrence1% more will die as a consequence.

Mathematical Model

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

The 10-Year mortality risk

Node negative women3%

1 to 3 - Node positive women13%

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%

Difference in benefit “if NN” vs. “if NP”

is

3.4% minus 0.8% = 2.6%

Let us assume the False Negative Rate of SNB is

9.7%

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%

Mathematical Model

Actual chance of missing a positive axilla in this patient is (AFN=ENP x

FNR)1%

Increased mortality due to axillary recurrence

1/10th of 1% = 0.1%

Mathematical Model

Actual chance of missing a positive axilla in this patient is (AFN=ENP 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%

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%

Tweak…Increase False Negative Rate to

20%

100%

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(FNR=20%)



chemotherapy”0.2% + 0.05%

= 0.25%

Unsuspected harm in this SNB-negative woman (60yrs, 0.5cm,

Grade i, ER-ve) because of omitting chemotherapy on




chemotherapy”1% + 0.26%

= 1.26%

False negative rate does not

matter…

But…

More Tweaks…

Increase tumour size and grade

Grade 2

Size 2cm

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(FNR=9.7%)




= 0.4%


ii, ER-ve) because of omitting chemotherapy on





= 0.82%

Tweaks…Increase tumour size, grade and reduce age

Grade 3

Size 2cm

Age 40


iii, ER-ve) because of omitting chemotherapy on





= 0.56%






chemotherapy”0.34%0.34% + 0.22%

= 0.56%






chemotherapy”0.70.7 + 0.46%

= 1.16%

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

NSABP B-32 Smoothed False Negative Rates

p = 0.30

Surgeon Case Number

0

20

Per

cen

tag

e F

alse

Neg

ativ

e

0 50 100 150

40

60

NSABP B-32 Smoothed Technical Failure Rates

p < 0.0001

0 50 100 150

0

5

10

15P

erc

en

tag

e T

ech

nic

al F

ailu

re

Surgeon Case Number

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

“barking dogs do not bite”

but

the dog doesn’t know that

SNB is appealing because it is precise

and logical But

breast cancer doesn’t know the rules!

In 10% of cases tumour skips the sentinel lymph node

Is there an alternative?

There isan alternative

Replace “dogma” with

“informed choice”

Edinburgh Studies

Prof Bob Steele, Mr Udi Chetty, Sir Patrick Forrest and colleagues

Mastectomy (417)Breast conservation (466)

RANDOMISATION

4- node sample

Axillary clearance

Outcome- local relapse, survival and morbidity

Technical Success

Sample Clearance

(202) (199)

Mean Number 4.8 20.6

Positive 85(42%) 80 (40%)

Failure 1 0

In 135 patients, randomisation was done after sampling

N Positive Additional Positive

Sample only 68 26 (38%) -

Sample+Clearance 67 26 (39%) 0

False negative rate

Overall Survival

Axillary Recurrence

Arm Oedema

4-node samplethe Edinburgh technique

Near 100% detection rate

Near 0% false negative rate

Low morbidity

Survival and local relapse equivalent

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

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.

RADIATION HAZARD

Applying the Mathematical model to 4 node sampl e

• FNR = 0%

• Effect of mortality = 0

• Effect of local recurrence = 0

Node positivity in trials of SNB

26%

On average,

1 in 4 patients have a second operation

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)

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 (don’t bother about FNR)

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.

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

Vote for choice

If you believe that Surgeons and

Patients should be allowed to

make an informed choice

Vote for the action

If you wish to just replace the

dogma of Axillary

clearance to the dogma of Sentinel node

biopsy

Vote against the action

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What is the best way to treat the axilla?