Clinical Trial Details
— Status: Recruiting
Administrative data
NCT number |
NCT04373655 |
Other study ID # |
EUBREAST 3 |
Secondary ID |
|
Status |
Recruiting |
Phase |
|
First received |
|
Last updated |
|
Start date |
April 28, 2020 |
Est. completion date |
April 2030 |
Study information
Verified date |
February 2024 |
Source |
European Breast Cancer Reseach Association of Surgical Trialists |
Contact |
Thorsten Kühn, Prof. |
Phone |
+49711 3103-3051 |
Email |
info[@]eubreast.com |
Is FDA regulated |
No |
Health authority |
|
Study type |
Observational [Patient Registry]
|
Clinical Trial Summary
The optimal surgical axillary staging technique in patients who convert from the clinically
positive to clinically negative lymph node status under neoadjuvant therapy (cN+ → ycN0)
remains to be clarified. Different strategies (axillary lymph node dissection, sentinel node
biopsy, targeted axillary dissection) are currently used in different countries. A
prospective analysis comparing these techniques regarding feasibility, safety, morbidity and
surgical effort is urgently needed. Due to high complexity and discordant recommendations, a
randomized trial comparing different techniques is hardly feasible. Therefore, the EUBREAST
study group decided to initiate a prospective cohort study as an international project that
aims at comparatively evaluating data on axillary staging after neoadjuvant therapy.
Description:
For many decades, axillary lymph node dissection (ALND) has been considered standard of care
in breast cancer (BC) patients. The procedure aimed at assessing the pN status to guide
adjuvant therapy decisions as well as ensuring adequate locoregional control. However, ALND
is associated with high morbidity and may therefore lead to reduced quality of life in BC
patients.
In women undergoing primary surgery, ALND as a staging tool has been replaced by the less
invasive sentinel lymph node biopsy (SLNB) without compromising the disease-free or overall
survival (DFS, OS). Since then, the therapeutic benefit of ALND in patients with clinically
occult metastasis in the sentinel lymph node (SLN) has been challenged as well. According to
the current national and international guidelines (e.g. ESMO, NCCN, German S3 guideline and
AGO recommendations) completion ALND can be safely omitted in selected patients with 1-2
positive sentinel lymph nodes.
The feasibility and safety of the SLNB after neoadjuvant chemotherapy (NACT) has been
controversially discussed, particularly regarding women who initially presented with positive
lymph nodes (cN+) and converted to ycN0 following NACT. In these patients, two large
prospective multicenter trials reported a false-negative rate (FNR) of 12 and 14%,
respectively, thus exceeding the generally accepted (albeit arbitrarily chosen) cutoff of
10%. The clinical relevance of an FNR > 10% and its impact on oncological endpoints (DFS, OS)
remains unclear. For this reason, numerous national guidelines still recommend ALND in these
patients.
Possible ways to further reduce the FNR in cN+ patients have been extensively discussed in
the recent years. In 2016, a novel surgical approach (TAD = targeted axillary dissection) has
been reported that consists of inserting a marking (e.g. a clip or a radioactive tracer) into
the metastatic lymph node before NACT. In patients in whom the marked lymph node (target
lymph node = TLN) and the sentinel node had been successfully removed, the FNR was as low as
1.4%. These retrospectively analyzed data from a prospective register support the hypothesis
that TAD can improve the relatively low success rates of SLNB and reduce the long-term
morbidity of patients undergoing axillary surgery in the neoadjuvant setting.
Several issues regarding currently used axillary staging techniques remain yet to be
clarified. Based on the unclear evidence, the guideline recommendations for the cN+ → ycN0
patients differ strongly. The current ESMO guidelines state that (1) SLNB may be carried out
in selected cases, and, if negative, further axillary surgery may be avoided and (2) the FNR
of SLNB alone can be improved by marking the biopsied positive node(s) to verify the removal.
In Germany, the S3 guideline (last version: 2020) recommends ALND in patients with initial
nodal involvement. In contrast, the German Working Group Gynecological Oncology (AGO) changed
their recommendations in 2019 and endorsed TAD as a technique of choice for this patient
subgroup. In several European countries (Sweden, Norway, Finland) ALND is still considered
standard of care for these patients. In others, such as Italy, most patients receive SLNB
alone without marking and removing the target lymph node. In the current NCCN guidelines the
TAD is considered an optional technique. A prospective analysis comparing different
techniques regarding feasibility, safety, morbidity and surgical effort is urgently needed.
Due to high complexity and discordant recommendations, a randomized trial comparing different
techniques is hardly feasible and therefore would not clarify currently open issues within a
reasonable timeframe.
Based on the lack of sufficient evidence and discrepancies between different national and
institutional standards, the EUBREAST study group (www.eubreast.com) decided to initiate a
prospective cohort study as an international project that aims at comparatively evaluating
data on axillary staging after NACT.