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What is the best way to treat the axilla?. 19 th century. 21 st century. Jayant S Vaidya MBBS MS DNB FRCSGlag PhD FRCS(Gen Surg). For. Axillary Sampling …with a choice of flavours… Clearance 4-node Sample Blue dye guided Sample Sentinel Node biopsy for … A CHOICE
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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)
For Axillary Sampling …with a choice of flavours… Clearance 4-node Sample Blue dye guided Sample Sentinel Node biopsy for… A CHOICE ofaxillary samplingprocedures
Once upon a time….. Tata Memorial Cancer Centre Axillary Clearance
Middlesex Hospital, University College London Axillary Clearance Sentinel Node Biopsy
Ninewells Hospital, University of Dundee Axillary Clearance Sunshine in Oct Axillary Sample – best of bothworlds Sentinel Node Biopsy Snowshine in Feb
False negative rateThe chance of missing a positive axilla Could cause harm by Axillary relapse Missed opportunity to institute systemic adjuvant therapy
Mathematical Model
Mathematical Model
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
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.
Mathematical Model • Age 60 years • Grade 1 • 0.5cm • ER negative • Estimated Node Positivity (ENP) = 10%
The 10-Year mortality risk Node negative women 3% 1 to 3 - Node positive women 13%
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%
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%) Increased Mortality due to axillary recurrence + Increased mortality due to “no 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 assumption that she is node negative (FNR=100%) Increased Mortality due to axillary recurrence + Increased mortality due to “no chemotherapy” 1% + 0.26% = 1.26%
More Tweaks… Increase tumour size and grade Size 2cm Grade 2
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%) Increased Mortality due to axillary recurrence + Increased mortality due to “no chemotherapy” 0.29% + 0.11% = 0.4%
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=20%) Increased Mortality due to axillary recurrence + Increased mortality due to “no chemotherapy” 0.6% + 0.22% = 0.82%
Tweaks… Increase tumour size, grade and reduce age Size 2cm Grade 3 Age 40
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 (FNR=9.7%) Increased Mortality due to axillary recurrence + Increased mortality due to “no chemotherapy” 0.34% + 0.22% = 0.56%
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 (FNR=9.7%) Increased Mortality due to axillary recurrence + Increased mortality due to “no chemotherapy” 0.34% + 0.22% = 0.56%
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 (FNR=20%) Increased Mortality due to axillary recurrence + Increased mortality due to “no chemotherapy” 0.7 + 0.46% = 1.16%
We need to inform our patients and take a shared decision about using Sentinel Node Biopsy?
NSABP B-32 Smoothed Technical Failure Rates 15 10 p < 0.0001 Percentage Technical Failure 5 0 0 50 100 150 Surgeon Case Number NSABP B-32 Smoothed False Negative Rates 60 40 p = 0.30 Percentage False Negative 20 0 0 50 100 150 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!
Is there an alternative?
There is an alternative
Replace “dogma” with “informed choice”
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
Sample Clearance (202) (199) Mean Number 4.8 20.6 Positive 85(42%) 80 (40%) Failure 1 0 Technical Success
False negative rate In 135 patients, randomisation was done after sampling N Positive Additional Positive Sample only 68 26 (38%) - Sample +Clearance 67 26 (39%) 0