SAN ANTONIO — Sentinel lymph node biopsy is as accurate as the traditional surgical practice of dissecting the entire axillary lymph node chain in women with breast cancer but inflicts far less nerve damage and fewer other complications, Mark Kissin, M.Chir., reported during a breast cancer symposium sponsored by the Cancer Therapy and Research Center.

The results of the first large-scale randomized trial of sentinel lymph node biopsy in breast cancer patients featuring comprehensive functional and quality of life assessment are so compelling that British health officials who have seen the data have directed that all U.K. surgeons undergo formal training in the technique, according to Dr. Kissin.

“There shouldn't really be a choice anymore. Sentinel node biopsy, for the patient, should be the standard of care,” he declared.

Dr. Kissin was a coinvestigator in the Axillary Lymphatic Mapping Against Nodal Axillary Clearance (ALMANAC) trial, a multicenter U.K. study in which 1,031 women with clinically node-negative breast cancer were randomized to sentinel lymph node biopsy (SLNB) or to the traditional surgical practice of dissecting the entire axillary lymph node chain. Surgeons who participated in the trial were required to have undergone systematic training in SLNB with demonstrated technical competence in its performance.

ALMANAC featured both patient assessments of functional status and quality of life as well as objective measurements of arm and shoulder morbidity, anxiety, and resource utilization at 1, 3, 6, 12, and 18 months. The 6-month follow-up data were the focus of presentations at the San Antonio meeting, although the 18-month data are being processed and should be available soon.

Only one-quarter of patients assigned to SLNB proved SLN-positive. That means three-quarters of women who undergo routine axillary node clearance needlessly experience the considerable associated morbidity that was documented in ALMANAC, Dr. Kissin, who is a surgeon at Royal Surrey County Hospital in Guildford, England, explained at the meeting.

During the first 3 months of follow-up, 83% of women who received standard axillary node dissection experienced at least one arm problem—lymphedema, shoulder stiffness and loss of range of motion, and/or sensory deficits; for 79%, the problem remained at 18 months.

For example, at 1 month, 62% of women randomized to axillary node clearance experienced sensory loss secondary to damage to the intercostal-brachial nerve, as did 43% at 6 months. In contrast, this was the case at 1 month in only 18% assigned to SLNB, and at 6 months in 16%.

It is worth emphasizing that ALMANAC employed an intent-to-treat analysis. Since all patients with a positive SLNB subsequently underwent full axillary clearance, and the associated morbidity was recorded on the SLNB side of the ledger, the study greatly underestimated the true benefits of having a negative SLNB.

At 6 months, 3% of women in the axillary clearance group had moderate to severe lymphedema, a rate that was sixfold greater than that of the patients in the SLNB group.

ALMANAC principal investigator Robert E. Mansel, M.D., reported that the SLNB group had significantly lower infection rates and operating times and shorter hospital stays.

There was no difference between the two study arms in anxiety levels as measured by the Spielberger State-Trait Anxiety Inventory.

That's an important finding, noted Dr. Mansel, who is professor of surgery at the University of Wales, Cardiff. Had patients undergoing SLNB experienced increased anxiety, he said, it might have cancelled out many of the other observed benefits.

ALMANAC isn't powered to reach definitive conclusions regarding breast cancer recurrence and survival. It's unlikely substantial differences exist in these end points between patients undergoing SLNB compared with routine axillary clearance, since patients with clinically node-negative disease enjoy a generally favorable long-term prognosis.

For most candidates, the substantial quality of life advantages and reduced morbidity entailed by SLNB will be the decisive factor.

For recurrence and survival data, oncologists will look to the results of the National Surgical Adjuvant Breast and Bowel Project B-32 trial, the largest-ever randomized prospective trial evaluating SLNB in clinically node-negative patients.

Thomas B. Julian, M.D., presented preliminary technical results from the phase III trial in which 5,210 participants were randomized to SLNB with or without immediate conventional axillary dissection.

A total of 26% of patients in both the SLNB and conventional axillary dissection groups proved SLN-positive. In 61.5% of SLN-positive patients, it was the only positive node.

The overall accuracy of SLNB was 97.2%, with a negative predictive value of 96.1% and a false-negative rate—“the number you've all been waiting for,” Dr. Julian said—a less than stellar 9.7%.

The false-negative rate was not affected by a surgeon's case experience, but it was influenced by the biopsy method employed. The highest false-negative rate—15.2%—occurred with excisional biopsy, for reasons not yet clear, according to Dr. Julian of NSABP headquarters in Pittsburgh.

Surgeons participating in NSABP B-32 had to complete a training protocol that included manualized instruction, a site visit, and performance of qualifying cases.

Researchers Embrace Sentinel Lymph Node Biopsy