Multidisciplinary considerations in the implementation of the findings from the American college of surgeons oncology group (ACOSOG) Z0011 study: A practice-changing trial

Surgical management of breast cancer has evolved from routine use of radical mastectomy to less disfiguring and extensive procedures, including breast-conserving approaches, for appropriately selected patients. Whereas this transition occurred over several decades, until recently axillary lymph node dissection (ALND) remained standard practice for patients with both node-positive and node-negative breast cancer. The introduction of sentinel lymph node dissection (SLND) was a major departure from ALND allowing for an alternative for nodal staging with less morbidity for the increasing population of patients presenting with clinically node-negative disease.1,2 Although some early studies suggested a survival advantage for patients who undergo ALND compared with no axillary surgery, the likelihood that removing negative nodes could improve outcomes has been questioned. SLND has become the standard of care for patients with clinically node-negative disease. With fewer nodes removed, pathologists can perform a more detailed examination. This allows for improved staging and increases the detection of small-volume metastases. As the population of patients with small burden nodal disease has increased, there has been a growing debate regarding the optimal treatment of node-positive disease. The consensus statement from the American Society of Clinical Oncology and the guidelines from the National Comprehensive Cancer Network recommend a completion ALND (cALND) when metastases are identified on SLND.3,4 These recommendations are supported by data from a meta-analysis of 69 trials, which included 8,059 patients who underwent SLND and cALND, where 53% of the patients with a positive SLN were found to have additional disease in non-SLNs.5 The cALND allows for assessment of the total number of nodes involved, which has prognostic and potentially therapeutic implications. The American Joint Committee on Cancer staging system includes designations for metastases in ≥10 lymph nodes (pN3), 4–9 lymph nodes (pN2), and 1–3 lymph nodes (pN1), as well as micrometastasis (pN1mi; >0.2–2.0 mm) and isolated tumor cells (pN0(i +); ≤0.2 mm).6 The extent of nodal disease may have implications in terms of local-regional control as well as use of systemic therapy and regional and nodal irradiation.7,8 Although cALND has been standard practice when SLNs are involved with metastatic disease, many have questioned the need for cALND in patients with small-volume metastases. The meta-analysis previously discussed showed that 53% of patients had additional nodes with metastatic disease on cALND.5 When considering patients with micrometastatic disease in the SLN(s), the rate of non-SLN involvement is as low as 20%; and for patients with isolated tumor cells the rate decreases to 12%.9,10 These findings have prompted a trend toward omitting cALND in selected patients. In an analysis of the surveillance, epidemiology, and end results (SEER) data from 1998 to 2004, up to 16% of SLN-positive patients did not undergo cALND—a trend seen in older women with low-grade, estrogen receptor (ER)-positive tumors. Considering only patients with micrometastasis in the SLN, the proportion treated with SLND alone increased from 21 to 38%.11 Similarly, a review of the National Cancer Data Base (NCDB) data from 1998 to 2005 revealed that 20.8% of patients with a positive SLN did not undergo cALND. To evaluate a more contemporary cohort, these authors analyzed data from patients diagnosed between 2004 and 2005 and found that the proportion of patients who underwent SLND alone increased in patients with micrometastases, whereas the proportion of patients who underwent SLND alone after macrometastases were identified in the SLN declined slightly during the same time period. At a median follow-up of just more than five years, there were no differences in axillary recurrence rates or survival for patients who underwent SLND alone versus SLND with cALND. This was true for patients with both micrometastases and macrometastases in the SLN.12 These data suggest that many clinicians do not believe that cALND plays an important role in the management of patients with small-volume metastases in the SLN. The American College of Surgeons Oncology Group (ACOSOG) recently reported the results of the Z0011 trial—a prospective, randomized trial designed to evaluate the impact of cALND on local-regional recurrence and survival in patients with early-stage breast cancer and a positive SLN. The purpose of this article is to review the results of the Z0011 trial and to discuss how these data can be implemented in multidisciplinary practice.