Randomized Trial Validates Advantages of SNB

SAN ANTONIO—A 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 anxiety scores.

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.