Response to the Letter to the Editor: Multidisciplinary Considerations in the Implementation of the Findings from the American College of Surgeons Oncology Group (ACOSOG) Z0011 Study: A Practice-Changing Trial

Excerpt

The letter from Drs. Batsis and Zoras reflects the widespread interest in the results of the ACOSOG Z0011 trial. We agree that thoughtful review of the data is warranted to apply the results in an appropriate population of patients with early-stage breast cancer. As mentioned, one consideration is that the trial did not enroll the 1,900 patients proposed to meet the primary objective. Although it is desirable to achieve the target accrual, several considerations suggest that this would not have altered the outcomes reported. The statistical considerations in the initial design were based on literature anticipating an 80% 5 year OS rate for patients with one to two positive nodes. However, SLND detects a lower burden of disease than ALND and this, coupled with advances in care, including improvements in imaging, pathology, radiation, and systemic treatment, are likely responsible for the better than anticipated 5 year OS seen in the trial (SLND 92.5% and ALND 91.8%).1 For ALND to confer an OS benefit, it would need to improve locoregional control. After a median follow-up of 6.3 years, axillary recurrence rates were 0.5 and 0.9% in the ALND and SLND groups, respectively,2 and it is unlikely that additional follow-up would alter these recurrence rates enough to impact OS. Finally, the issue of power is not as relevant in a positive trial, such as Z0011. It was designed as a noninferiority trial with a noninferiority margin of a one-sided hazard ratio of less than 1.3, indicating that SLND alone is not inferior to ALND. The confidence interval (CI) did not cross 1.3, hence a positive trial. If the trial had been negative and the CI crossed 1.3, there would have been more concern regarding failure to meet target accrual as each event would cause the CI to become narrower and it may have failed to cross 1.3. …