Management Of Axilla

Two main questions in management of axilla are :

  • Optimal extent of axillary dissection
  • Whether radiotherapy can substitute for surgery
    • Specially in the management of patients with clinically-uninvolved (cN0) nodes.

In terms of treatment of axilla, one should ask herself:

  • What to do after positive one lymph node in sentinal lymph node biopsy?
  • What to do after 1-3 LN+ after BCT or Mastectomy?

Assessment of Axilla:

  • Standard at the moment is Sentinal Lymph Node Biopsy (SLND)
  • If that become positive
    • Usually ALND
      • Sufficient ALND is considered > 10 LN
      • If >3 LN+ and/or ECE+
        • RT to axilla + supraclavicular LN
      • If 1-3 LN+
        • if ALND < 10
          • RT to axilla and SCL
        • If sufficient ALND
          • No further treatment

Now you can find evidence behind why we do it this way!

Extent of Axillary Dissection

There is a Japanese trial(by Tominaga)

  • 1991-93
  • Post-Mastectomy patients
  • Compare results between:
    • “complete” axillary dissection (that is, a dissection removing nodes at Levels I, II, and III)
    • Limited dissection (removing only the Level I and II nodes).
  • There was no post-op RT
  • No difference in the morbidity of surgery

RESULTS

  • No difference in overall survival at 10 years
  • Nonsignificant difference in disease-free survival at 10 years favoring the Level III arm
    • (60% versus 53%) in the node-positive patients.

Axillary Radiation Treatment vs Surgical Axillary Lymph Node Dissection

AMAROS TRIAL

After Mapping of the Axilla: Radiotherapy Or Surgery

  • This is an ongoing Randomized Trial which will answer the question wether axillary RT is equivalent to Sx after + SLN.
Untitled.png?ukey=d5535053f557e0ba9980408c9b2aaa2f9c0adcd2
  • Basically three groups of patients :
    • Those with negative SLN and No Further Therapy
    • Those with positive SLN and ALND
    • Those with positive SLN and RT to level I and II
    • There is also a 4th group in which the sentinal node is not found and go through complete axillary dissection.
  • Main objective
    • RT has equivalent local/regional control for patients with proven axillary lymph node metastasis by sentinel node biopsy with reduced morbidity instead of axillary lymph node dissection.
  • Second objective
    • Adequate axillary control can be obtained by not subjecting patients with a negative sentinel lymph node to axillary lymph node dissection.

Selection criteria:

  • Tumor Size : 5 mm - 5 cm
  • Clinical node negative

RESULTS

  • Subset analysis
  • First 2000 patients. SLN identification rate 97%

Outcome:
In General! :

  • SLN- : 65%
  • SLN+ : 34%
    • Macromets 63%
      • Chance of further LN+ : 41%
    • Micromets 25%
      • Chance of further LN+ : 18%
    • ITCs 12%

Institut Curie Trial

This is another randomized trial (by Louis-Sylvestre) which compared RT vs Sx:

  • Basically all patients had lumpectomy followed by RT to breast
      • 55 Gy + 10-15 Gy as boost (total: 65-70 Gy)
  • Axillary management —> two group of patients
    • ALND
      • level I and lower level II
        • If any patient in this group had +LN ==>
          • XRT to SCLV and IM nodes
    • Axillary RT
      • RT to axilla and IMN. Dose to axilla was 50 Gy; dose to SCLV and IM nodes was 45 Gy.
  • 1982-87 - 658 patients
  • Clinically N0
  • T < 3cm
  • Chemo and Hormonal therapy allowed if required.

RESULT

  • Survival (89% vs. 87%)
  • After 15years —> No difference in OS or DFS
    • 15-year OS 75% vs 75%
  • Axillary recurrence after 15yrs:
    • RT —> 3%
    • Sx —> 1%
    • Significantly different ; But RT still a reasonable alternative.

NSABP B-04 (Fisher)

This is an important study. This is the study based on which, the radical mastectomy moved to total mastx. Also this study provided the evidence that For years (from 1895) Halsted method of Mastectomy (Radical Mastectomy) was the standard of care for breast Ca.

To understand this trial you should know Types Of Mastectomy. If you don't know, check!

Primary research question(s):

For clinically NEGATIVE LN:

  • Is Total Mastectomy + ALND of those who subsequently develop positive nodes as effective a therapy as is radical mastectomy in patients with clinically negative axillary nodes?
    • Basically can we salvage axilla if we do not assess it?!
  • Is total mastectomy with postoperative regional radiation as effective as radical mastectomy or total mastectomy with postponement of axillary dissection until positive nodes occur?
    • What if we don't dissect but we give RT; maybe that compensate for dissection!

For clinically POSITIVE LN:

  • Are radical mastectomy and total mastectomy with radiation equivalent procedures in patients with clinically positive nodes?
  • Is there biological significance to be gained that confirms or repudiates the worth of en bloc dissection in cancer surgery?

DESIGN:

For clinically NEGATIVE LN:

  • 1/3 —> Radical Mastectomy
  • 1/3 —> Total Mastectomy + regional RT
  • 1/3 —> Total Mastectomy

For clinically POSITIVE LN:

  • 1/2 —> Radical Mastectomy
  • 1/2 —> Total Mastectomy + RT
  • 1977 (1971-4)

RESULT

  • Out of those who were clinically negative LN eventually 14.2% developed histologically positive nodes ==> ALND
    • Mean time : 12m
    • Range of time to axillary disease: (2-49m)
  • Out of those who were clinically positive LN 2% histologically were LN-.
  • No difference in OS or axillary recurrence.

For clinically NEGATIVE LN:

10 YEARS DFS DDFS OS
RM 47 58 58
TM+RT 48 57 59
TM 42 55 54
25 YEARS DFS RFS DDFS OS
RM 19 53 46 25
TM+RT 13 52 38 19
TM 19 50 43 26

Clinically POSITIVE axilla:

10 YEARS DFS DDFS OS
RM 29 39 38
TM+RT 25 40 39
25 YEARS DFS DDFS OS
RM 11 36 32 14
TM+RT 10 33 29 14

The story behind Sentinal Node Biopsy:

After NSABP-04 the practise of ALND started to be quitted. However there were evidence that axillary recurrence can be as high as 30% in un-assessed axilla in long-term survivors. Also there were evidence that axillary recurrence might affect survival.
So axillary assessment came into practise this time as sentinal node biopsy.

Comparison of SLNB vs ALND

NSABP-032
  • Clinically NODE NEGATIVE
  • Is sentinel node resection alone is equivalent to sentinel node resection followed by conventional axillary dissection?
    • That means if OS, Axillary Recurrence and DFS is the same wether or not you perform a SLNB or ALND
    • Also the prognostic factor of both should be the same.
NSABP-B32?ukey=5427e70d48b69354fd83d0e9f942b8fba7f59791
RESULT
  • SLN+ in both arms 26%
    • In those who had ALND —> 61% had no further disease.==> 40% chance for further disease.
  • If SLN- (74%)
    • ALND- 96%
    • ALND+ 4%
      • False Negative rate 10%
        • If only one SLN removed false negative up to 18%
  • Overall accuracy 97%.
  • OS, DFS, and regional control were statistically similar between groups.

Morbidity :

Bottom line: Less morbidity in SLNB

  • Shoulder range of motion: deficit of 10% or more
    • ALND : 75%
    • SLND : 41%
    • Peak at 1 week
  • Lymphedema and Arm volume: increase of 10% or more(at 36m)
    • ALND : 14%
    • SLND : 8%
  • Sensory: numbness or tingling (peaked at 6 months)
  • ALND : 23%
  • SLND : 10%
ALMANAC
  • Stopped early due to perceived loss of equipoise, with better QoL in SLN arm
  • Arms
    1. SLN
      • SLN+ then:
        • Delayed Axillary Surgery or
        • Axillary RT
    2. Standard axillary surgery
      • Level I-III ALND (75%)
      • 4 node sampling (25%)

RESULTS
Technical outcome: SLN identified in 98%
Clinical outcome:

  • Lymphedema
    • SLN 5%
    • ALND 13%
  • Numbness
    • SLN 11%
    • ALND 31%

Conclusion: SLN is associated with reduced arm morbidity and better quality of life

a. M.D. Anderson → study the pattern of nodal failure in Mastx with no XRT
o 1031 patients with level I and II dissection + chemotherapy with NO XRT;
o Risks associated with recurrence:
• > = 4 LN+
• >20% involved axillary nodes
• gross ECE
b. Post-Mastectomy XRT for LN+ 1-3
o British Columbia
• Risk of >20% LRR for pts with 1-3 LN+ and one of the following:
a. age < 45
b. ER negative
c. medial location
d. >25% LN+