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Scaling back on lymph node dissection: time for a new standard?
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In the past 1 to 2 years, there has been a lot of new information from clinical series and randomized trials assessing outcomes from sentinel lymph node biopsy and the omission of full axillary lymph node dissection. This has coincided with our appreciation that lymphedema is more prevalent and affects quality of life to a greater extent than we believed earlier.
The practice of sentinel lymph node biopsy (SNLB) was adopted quickly before large-scale trials were able to define a false-negative rate in the 5% to 10% range, and there is a definite learning curve in the proficiency and accuracy associated with this procedure. Outcomes from larger-scale randomized trials have now confirmed a more rapid short-term recovery of function and lower long-term lymphedema rates with sentinel compared with full axillary node dissection without any increase in the risk for locoregional or distant recurrence.
Of all the advances in breast cancer therapy, SNLB is one that is directly relevant to the patient experience. This is no small matter, because one of the key barriers to women seeking evaluation and care of a breast mass or mammographic abnormality is the fear of therapy and its consequences.
The next bold question to be posed has been a little harder for the medical community to digest. Can full axillary node dissection be avoided even in the presence of one or more positive sentinel nodes?
Low mortality, recurrences
The American College of Surgeons Oncology Group Z0011 trial was designed to address this question in patients with clinical T1 or T2 and N0 breast cancer who were to receive whole-breast opposing tangential-field radiation therapy. The endpoint of this trial was survival, but as the trial progressed, it became clear that the mortality rate was too low to show a difference, even if the planned 1,900 patients were all accrued. Therefore, the study was closed early with 856 patient enrolled, but the very low number of deaths (OS, 92%) and locoregional recurrences (overall, 3.6%) numerically favored the SNLB group, although the differences were not statistically significant.
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The authors said there is a very small chance that the number of recurrences would end up being higher in the SNLB group. At the 2011 Miami Breast Cancer Conference, there was considerable debate as these and other data were presented: Is the surgical community ready to omit dissection in the case of a positive SLNB?
On one hand, the under accrual coupled with short follow-up of a disease with a long natural history make such an adoption difficult. On the other, the risk for lymphedema for a negligible gain in survival, if any, does not seem to serve the patient well. The consensus, at least from this conference, reflected a strong reluctance to abandon a full dissection with a positive sentinel node. But the discussion revealed that this was an uncomfortable reluctance because for the first time, it contradicted the available data, even if the data were not felt to be as solid as they could be.
Small steps
Are we at a point of paralysis on this issue? Not really, because slow adoption can actually be a good thing. It allows physicians to initially select patients for a new procedure that have the smallest chance of harm in the event that we made the wrong conclusion. Perhaps it is best to start with omitting axillary lymph node dissection (ALND) with only one positive sentinel lymph node and with smaller tumors of lower grade. As the data from this study matures (not that it will ever have the statistical power originally planned), it may give us more confidence to push the envelope with higher risk cases and more positive sentinel nodes. Of course, the omission of ALND for a positive sentinel node has to be done in the context of the trial design, specifically in patients with tumors smaller than 5 cm who will receive radiation therapy.
Also in this trial, 96% of patients received some form of systemic therapy, and 58% received chemotherapy. Most agree that the broader use of systemic therapy has lowered the overall recurrence and mortality rates in early stage trials, with modern day randomized trials now requiring several thousand patients. Yet, it is not clear to what extent systemic therapy is needed to negate a potential difference based on the extent of lymph node dissection. Nevertheless, the planned use of systemic therapy might be another requirement for early adoption of ALND omission for positive sentinel lymph node.
Even if the act of additional node removal does not influence outcome, might the information gained from identifying additional positive nodes affect radiation and systemic therapy decisions that would modulate recurrence risk? Although this question cannot be easily answered, it is tempered by the growing awareness that staging might be trumped by biological factors. The application of gene profiling to large tissue sets has certainly supported this new hierarchy. However, for a given gene profile score, the number of nodes still matters and predicts a higher risk of recurrence. For the moment, it appears that anatomic staging is still important, perhaps explaining reluctance to adopt the Z0011 findings.
The trend for more focused local therapy, both surgical and radiation, is a welcome advance. At the same time, it is clear that local control affects OS — particularly in younger patients who have a long life ahead. Balancing these facts with early data from an underpowered trial is indeed difficult. Currently, it makes sense to discuss these issues with each patient and to omit dissection in selected cases that reflect both the level of comfort of the physician and patients and the eligibility criteria of the Z0011 trial.
Debu Tripathy, MD, is a HemOnc Today Editorial Board member and professor of medicine, University of Southern California, Norris Comprehensive Cancer Center. He is also course director for the Miami Breast Cancer Conference. He reports no financial disclosures.
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