Completion Axillary Lymph Node Dissection for Breast Cancer: Immediate Versus Delayed Versus None

Axillary lymph node dissection (ALND) for women with breast cancer was relegated to the status of a mere staging procedure long ago. More recently, even this role has been reduced because sentinel lymph node (SLN) biopsy has been shown to predict which patients will or will not have positive nodes in the axilla with a high degree of accuracy. The main advantages of SLN biopsy over standard ALND are more accurate staging and decreased morbidity, especially lymphedema and arm dysfunction. The benefits of replacing ALND with SLN biopsy are undeniable,butthistransitionhasalsoraisednewquestions.Althoughthe SLNbyitselfwill indicatethenodalstatus(positiveornegative), ithasbeen routine for most women with positive sentinel nodes to undergo a completion ALND (cALND), even though other nodes may contain metastases in only 40% of these patients. The American College of Surgeons Oncology Group (ACOSOG) Z0011 trial was designed to determine whether cALND was beneficial in patients with positive SLN, but was terminated because of poor accrual; so the question of SLN biopsy alone compared with cALND remains open in this group of patients. Meanwhile, a number of variables and methods have been described to help determine the likelihood of finding positive non-SLNs, which may influence patients’ and doctors’ decisions about whether a cALND is worthwhile. The role of cALND in patients with micrometastases remains particularly unsettled. In most centers, SLN are routinely sent to pathology for intraoperative assessment, with cALND being performed immediately if metastases are identified. False-negative results intraoperatively lead to the need for a secondary or delayed cALND procedure, which has generally been assumed to be less desirable. However, in this issue of Journal of Clinical Oncology, John Olson and colleagues report that among 1,003 patients enrolled in the ACOSOG Z0010 and Z0011 trials, short-term morbidities were actually higher with immediate cALND compared with delayed cALND, and late quality of life indicators were not different between the two approaches. A number of different histopathologic methods have been advocated for intraoperative SLN assessment, with the goal of maximizing sensitivity to avoid the need for a second operation, while not sacrificing specificity. Fortunately, the false-positive rates reported have been extremely low, so that unnecessary cALND occurs only rarely, but false-negativeratesmaybeashighas50%,resultingintheneedfordelayed cALND. The results reported by Olson and colleagues force us to ask—if immediate cALND is not better, then why bother with intraoperative examination of SLNs? The quick answer is that avoidance of a second operation (and a second anesthetic) has rather obvious benefits not measured in this study, such as decreased patient anxiety, lower costs, less time away from work, and less delay to the start of adjuvant therapy. Moreover, because the ACOSOG trials did not include women having total mastectomies, these results do not necessarily apply to such patients, where the consequences of re-operation may be greater, particularly in women who have undergone immediate reconstruction. Potential consequences of a second operation in those patients include damage to the blood supply to a free flap, infection of a prosthetic implant, and a much more difficult ALND because of the presence of a flap or tissue expander. In the post-SLN era, the need for cALND in all patients with positive SLN is now being challenged, and the main argument in favor of delayed cALND is that it allows for a discussion of the pros and cons with the patient before proceeding. This is analogous to the abandonment of frozen section examination of breast biopsies and immediate mastectomy for cancers; when there is equipoise between the options to consider, then the patient should have a chance to have input rather than agreeing to hypothetical procedures. This may be particularly important for patients with micrometastases in SLN or other factors that may predict a low likelihood of having other positive nodes. A number of such variables, such as tumor size, grade, lymphovascular invasion (LVI), estrogen receptor (ER) status, and method of detection of micrometastases have been described in the past few years. For patients who are judged to have a low likelihood of having positive non-SLN or in those who have overriding concerns about the consequences of an ALND, the data presented in the Olson et al article make it reasonable to omit intraoperative examination of the SLN selectively, chancing a second procedure. Fortunately, the same factors that predict low risk of positive non-SLN are often associated with a lower likelihood of a positive SLN, so that the frequency of having to reoperate on these patients should be low. But why not take this approach in everyone electing a SLN biopsy? The answer to this question is also articulated in the data presented here from the ACOSOG trials: identifying positive SLNs on intraoperative pathology and performance of an immediate cALND was associated with a much higher likelihood of finding positive nonSLN (43% v 27%) and a greater number of positive non-SLN (median, 2 v 1). This is also consistent with the finding that patients undergoing immediate cALND had, on average, larger tumors and more ER-negative tumors. All of these findings are consistent with the fact that finding SLN metastases on intraoperative examination is likely to be associated with larger tumor burden and larger foci of JOURNAL OF CLINICAL ONCOLOGY E D I T O R I A L VOLUME 26 NUMBER 21 JULY 2