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EDITORIALS |
From the Joyce Eisenberg Keefer Breast Center and the John Wayne Cancer Institute at Saint John’s Health Center, Santa Monica, California.
Correspondence: Address correspondence to: Armando E. Giuliano, MD, John Wayne Cancer Institute, 2200 Santa Monica Blvd., Santa Monica, CA 90404; Fax: 310-998-3995; E-mail: giulianoa{at}jwci.org
In this issue1 of the Annals of Surgical Oncology, Shivers et al. present the results of the Department of Defense’s lymphatic mapping trial. As such, this represents one of the largest multicenter studies to date (965 patients) to investigate the technical issues of selective (sentinel) lymph node dissection (SLND). The main aims of this study were 2-fold: to determine the success of teaching community surgeons the technique of breast lymphatic mapping and to assess the role of preoperative lymphoscintigraphy in this process. This study, similar to other multicenter trials evaluating breast SLND,2,3 demonstrates that surgeons can master the technique of SLND after a short, but intensive, learning period (10–30 cases). Surprisingly, the rate of successfully identifying an axillary sentinel lymph node (SLN) in the community and regional hospitals included in this study was substantially lower (85.2%) than that of the university hospitals (91.4% to 92.8%). Nevertheless, the small (4%) false-negative rate noted in this study indicates that the technique of SLND is ready to move from the university setting into the community.
There are important "pearls" that may be gleaned from this study regarding the successful performance of SLND. First, a nonstained lymph node with a blue afferent channel should be classified as an SLN which the dye has not yet reached or whose uptake of dye may be blocked by overgrowth of tumor. We reported this phenomenon, which we frequently noted during the development of SLND, in 1991 when we included patients with palpable malignant lymph nodes. We also occasionally noted unstained nonmalignant lymph nodes with blue afferent channels, which we speculated might have been because of insufficient time from injection or inadequate volume of injected dye to stain the SLN in these cases. Second, the accuracy of SLND may depend on whether an intact tumor or a biopsy cavity is present. Surgeons in this study identified the SLN only 82% or 86% of the time after core or excisional biopsy, respectively; the SLN was identified 89% of the time after fine-needle aspiration. It is somewhat unclear if these small differences are significant. Our experience with SLND indicates that there is no significant correlation between either the size of the tumor or the method of biopsy and the ability to identify the SLN.4 Lastly, the lymphoscintigram must include a lateral image to unmask the axillary SLN from the star artifact of the primary tumor. This is a very important technical point for lymphoscintigraphy.
As this study shows, the success of breast SLND depends on the well-coordinated efforts of a multidisciplinary team of surgeons, pathologists, radiologists, and operating room staff. In any setting, demonstration of a < 5% false-negative rate should be achieved before this team undertakes SLND without completion axillary lymph node dissection (ALND). The authors have used a combination of vital blue dye and radiocolloid in a majority of their patients, which is probably the easiest way to learn the technique. The optimal technique for identifying the SLN will continue to be debated as technical innovations, such as alternative injection sites and new agents, are described. The present study shows that the SLN is successfully identified only 82% of the time from inner quadrant tumors. Collectively, these results and the results of other studies clearly support the use of multiple agents to identify the SLN in obese patients, large breasts, and medial tumors.5,6 Several years ago we began to use radiocolloid in addition to dye in these circumstances.
The role of SLND in the management of breast cancer patients continues to evolve. The immunohistochemical and molecular analysis of the SLN may provide significant additional prognostic information that cannot be obtained from analysis of either the primary tumor or the entire axillary contents. This is being investigated by a number of different groups nationwide and as part of the American College of Surgeons Oncology Group (ACOSOG) Z0010 study. Most experienced centers have long omitted ALND for patients with a negative SLN, and some centers now are omitting ALND for an SLN with micrometastases detected only by immunohistochemistry. This study noted that the SLN was the only positive lymph node in 63% of the cases. The question of whether ALND may be omitted for certain breast cancer patients with a positive SLN7 is being addressed as part of the ACOSOG Z0011 study. Many of the centers that contributed to the Department of Defense’s study are contributing to this study.
There are several important questions raised by this study. Can the results of preoperative lymphoscintigraphy spare certain patients (i.e., those without demonstrable axillary drainage) from any type of axillary staging? Lymphoscintigraphy failed to identify any preoperative drainage 34% of the time in this study. However, the combination of blue dye and the more sensitive handheld gamma probe identified an SLN in 67% of these patients. Approximately 11% of the 617 patients who underwent lymphoscintigraphy did not have an SLN localized preoperatively or intraoperatively; half of these patients might still be expected to have disease in level I or II lymph nodes. Clearly preoperative imaging studies alone would not be able to determine whether selected patients could be excluded from any form of axillary staging. What is the clinical significance of multidirectional lymphatic flow? How should we manage patients with extra-axillary (i.e., internal mammary and supraclavicular) drainage, which the authors identified 19% of the time by lymphoscintigram? The identification of extra-axillary drainage may have profound staging and/or treatment implications, such as the widening of radiation treatment fields or upstaging cancers with the discovery of metastatic disease in internal mammary or supraclavicular lymph nodes. Nevertheless, as the authors suggest, it is unclear whether the clinical behavior of these upstaged tumors is really significantly different than that of tumors with metastases only in the axilla. We acknowledge this uncertainty and continue to address extra-axillary drainage on a case-by-case basis. These questions will be answered in multi-institutional trials.
This well-done study should serve as a model for community and regional hospitals that are interested in performing lymphatic mapping as part of the care offered to breast cancer patients. Clearly, these hospitals must be able to achieve an SLN identification rate of 85% and a false-negative rate of <5% before omitting ALND. This study capably demonstrates that these goals can be met if hospitals use a formal training course, a learning phase, and the coordinated efforts of a multidisciplinary team. There are a number of questions that remain to be answered. It is anticipated that the results from ongoing studies may answer these questions and provide additional evidence as to the clinical benefit of performing SLND in breast cancer patients. This group of investigators is to be congratulated for their contributions to the teaching and dissemination of sentinel node biopsy.
Footnotes
Supported by the Leslie and Susan Gonda (Goldschmied) Foundation, Los Angeles, CA; the Ben B. and Joyce E. Eisenberg Foundation, Los Angeles, CA; the Associates for Breast and Prostate Cancer Studies, Santa Monica, CA; and QVC and the Fashion Footwear Charitable Foundation, New York, NY.
Received for publication April 5, 2002. Accepted for publication April 22, 2002.
REFERENCES
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