Factors influencing accrual to ACOSOG Z0011, a randomized phase III trial of axillary dissection vs. observation for sentinel node positive breast cancer

Abstract

601 Background: The American College of Surgeons Oncology Group opened a phase III randomized trial to assess the value of axillary node dissection (ALND) after positive sentinel node biopsy (SNB). After 5.5 years, the trial closed due to poor accrual with only 891 patients of the planned 1900 accrued. The purpose of the current analysis is to assess factors impacting accrual to Z0011. Methods: Women having SNB for T1 or T2 breast cancer were eligible for participation in the Z0010 trial to assess the significance of micrometastases identified by immunohistochemistry. If the SN was positive for metastasis by H&E, the patient was eligible for randomization on Z0011 trial. Intraoperative (IOR) and postoperative randomization were allowed. Patients having SNB outside of the Z0010 trial were eligible. Results: 1003 patients from the Z0010 trial were eligible for randomization on Z0011. Of these, only 37% were entered in Z0011. Z0010 participants accounted for 42% of patients in Z0011. 16% of patients not randomized refused ALND. 69% of those not randomized had ALND. 67% of these had no additional positive nodes. Only 14% had ≥ 4 positive nodes. Enrollment of eligible Z0010 patients varied by type of institution: 25% at academic sites, 42% at teaching affiliated and 53% at community (p < 0.0001). By geographic region, sites in the South entered 42% of eligible patients compared with 24–36% in other geographic regions (p=0.0027). Only 32% of patients were consented for IOR based on frozen section of the SN. Sites in the South and West were less likely to use IOR (25% and 28%) compared to Northeast and Midwest (45% and 46%) (p < 0.0001). 110 sites participated in Z0011, yet 48% of patients were enrolled by 10% of sites. Conclusions: Failure of this important trial to accrue as planned is likely related to the clinical bias of physicians and patients to standard ALND. Yet, 2/3 of patients had no additional positive nodes and extensive nodal disease was infrequent. While it was thought that IOR might improve accrual to Z0011, the most successful sites were less likely to use this approach. Community surgeons were most successful in randomizing patients. [Table: see text]