SAN ANTONIOA randomized, multicenter trial from the
United Kingdom has demonstrated what clinicians have instinctively felt: that
sentinel node biopsy (SNB) is associated with less morbidity and better
quality of life than standard axillary node surgery. Professor Robert E.
Mansel, University of Cardiff, Wales, presented the results of the Axillary
Lymphatic Mapping Against Nodal Axillary Clearance (ALMANAC) trial at the 27th
Annual San Antonio Breast Cancer Symposium (abstract 18).
Morbidity commonly associated with axillary clearance
includes arm muscle weakness, stiffness, numbness, impaired mobility, pain,
and lymphedema. Up to 83% of women have at least one of these problems, and
79% have a persistent problem.
Results from several small, nonrandomized, mostly
observational studies suggest that SNB decreases arm morbidity. "A high
proportion of patients have symptoms, many of which are persistent. The
question has been whether we actually know that sentinel node biopsy is
associated with low morbidity," Dr. Mansel said. This information is now
obtained from "the first large multicenter randomized controlled trial of SNB
with a comprehensive quality-of-life assessment . . . producing an
astronomical amount of data," he said.
ALMANAC included 1,031 clinically node-negative invasive
breast cancer patients randomized to SNB (n = 515) or axillary clearance (n =
516). Patients with positive sentinel nodes (26% of the cohort) went on to
axillary clearance or received axillary radiotherapy. Patients were followed
periodically up to 18 months. The current analysis is based on 6-month data.
Patients with positive lymph nodes who received further
treatment remained in the SNB arm for analysis, "which understates the benefit
of SNB but is a purer way to analyze the data," Dr. Mansel said.
The randomized study was preceded by a validation phase.
Surgeons achieving a set standard (localization rate of at least 90%;
false-negative rate of 5% or less) in a consecutive series of 40 patients were
allowed to participate in the randomized phase. Most surgeons reached the 90%
success point after 10 cases.
Primary endpoints were quality of life (by FACT-B+4 domains
and the Spielberger State-Trait Anxiety Inventory); arm and axillary morbidity
(sensory loss, shoulder stiffness, lymphedema, drain usage, operative time,
hospital stay, and time to return to normal activities); and resource costs. A
newly validated arm morbidity instrument was used for scoring these symptoms.
Arm morbidity was assessed via self-assessment
questionnaires and by objective assessment of arm volume changes (the
contralateral arm was used as a control), shoulder function, and sensory
deficits. The results were cross-correlated with the surgeon’s information
regarding possible nerve damage.
SNB Superior in Several Measures
"Overall, in the first 6 months, SNB yielded lower
morbidity, no increase in anxiety [fears that cancer is not detected], less
use of hospital resources, and time savings," Dr. Mansel reported.
At 6 months, patients in the SNB arm reported significantly
better quality of life, as demonstrated by:
■ Greater decrease in
the trial outcome index, which was the sum of physical, functional, and breast
cancer concerns subscales.
■ Less decrease in the
FACT-B+4 score (all subscales).
■ Greater increase in
the quality-of- life score for arm morbidity.
■ No difference in
Significant differences in symptoms between the arms are
shown in the Table on page 2.
Several other differences were significant. Drains were
necessary for 79% of the standard arm vs 17% having SNB, and percentage of
patients returning to normal activities at 6 months was 93% vs 96%,
respectively. Hospital stay was 5.4 days vs 4.1 days (which includes second
surgeries for about one-quarter of SNB patients); this amounted to 589 total
hospital days avoided with SNB during the trial period. There were also trends
favoring SNB in shorter operative time (20 minutes with standard surgery vs 17
with SNB, which included reoperations) and less postoperative infection (15%
vs 11%, respectively).
Kent Osborne, MD, director of the Breast Center, Baylor
College of Medicine, Houston, commented that the advantages of SNB were
underestimated due to the intent-to-treat analysis. "If you take out the 26%
of cases that were positive with SNB [and went on to have axillary clearance],
you would see a substantial lowering in the incidence of side effects."
Dr. Mansel agreed and said that a sub-analysis is now
underway. "These findings lead to the conclusion that there should not be a
choice anymore. Sentinel node biopsy must be the standard of care for these
patients," he said.