In an editorial accompanying the article by Boughey et al, Monica Morrow, MD, and Chau T. Dang, MD, of Memorial Sloan-Kettering Cancer Center, New York, question whether sentinel lymph node biopsy can be considered a part of standard management in patients with initial clinically node-positive disease. They point out that the finding in the Boughey et al study that the false-negative rate of sentinel node sampling dropped below 10% only when three or more sentinel nodes were removed is similar to the findings of the SENTINA trial, in which initially node-positive patients had to be clinically node-negative after neoadjuvant chemotherapy in order to undergo sentinel lymph node biopsy.

In addition to the findings of the SENTINA trial suggesting that false-negative rates are not improved by selecting patients with clinically node-negative disease following neoadjuvant chemotherapy for sentinel lymph node biopsy, the two studies together clearly show that only when at least three lymph nodes are harvested during sentinel node biopsy is the false-negative rate for patients initially presenting with clinically node-positive disease comparable to that in patients initially presenting with clinically node-negative disease who undergo sentinel lymph node procedures after chemotherapy or in patients who have sentinel lymph node biopsy prior to chemotherapy.

Nevertheless, they point out, “Whether the random removal of additional nodes for patients with fewer than 3 [sentinel nodes] results in equivalent false-negative results is uncertain, and random sampling cannot be advocated as standard management.”

Importance of False-Negative Rates?

Drs. Morrow and Dang go on to question the assumption that false-negative rates > 10% for sentinel node biopsy is important, noting that a large experience with sentinel node biopsy in patients having surgery before chemotherapy shows an incidence of clinical nodal recurrence substantially lower than the false-negative rate. As examples, they cite the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-32 trial, in which the false-negative rate of sentinel node biopsy was 9.8% and only 0.7% of patients developed their first recurrence of cancer in the axilla, and the American College of Surgeons Oncology Group (ACOSOG) Z0011 trial, in which almost all patients received systemic therapy and radiotherapy and in which 27% of patients receiving sentinel lymph node biopsy had axillary lymph node cancer that was not removed during surgery but only 0.9% had their first cancer recurrence in the axilla. This 27% figure is similar to the 31% false-negative rate after the removal of one sentinel node in the Boughey et al study.

As the commentators stated, “The patients who did not have [axillary lymph node dissection] in the ACOSOG Z0011 study did not experience an excess of distant metastases and death … strongly arguing that undetected microscopic cancer in patients presenting with clinically node-negative disease does not result in a clinically important increase in recurrences despite being left in place.”

Further Considerations

Finally, the commentators point out that decisions about using systemic therapy after neoadjuvant therapy are not dependent upon identifying residual cancer in lymph nodes when all the planned chemotherapy is given preoperatively to maximize the cancer response. They note that identification of residual lymph node cancer may be important in trials of new agents in which post-neoadjuvant treatment decisions may depend on detection of residual disease. However, in considering what information can be derived from an initial sentinel node biopsy, they maintain that it must be recognized that patients with residual cancer after neoadjuvant therapy have some level of resistance to systemic therapy. Such patients might require more aggressive local therapy such as complete axillary lymph node dissection or axillary radiation therapy.

In this regard, Drs. Morrow and Dang state, “Because there is no information regarding long-term local cancer control or survival for patients initially presenting with clinically node-positive disease who receive neoadjuvant therapy, but have a 20% to 30% rate of residual cancer in the axilla following [sentinel node] biopsy, we do not believe that [sentinel node] biopsy, regardless of the number of [sentinel nodes] removed, can be considered standard management for these patients.”

It may be that in the future, identification of residual disease after neoadjuvant therapy will change subsequent systemic management, in which case prognostic information obtained from residual nodal disease after neoadjuvant therapy is likely to become increasingly important in determining the need for additional therapy. “If that is true,” concluded the commentators, “research in ways to improve the performance of [sentinel node] biopsy after neoadjuvant therapy is needed for this approach to become a viable management strategy.” ■

Disclosure: Dr. Morrow and Dr. Dang reported no potential conflicts of interest.

Reference

1. Morrow N, Dang CT: Editorial. Sentinel node biopsy after neoadjuvant chemotherapy: A new standard for patients with axillary metastases? JAMA 310:1449-1450, 2013.