Abstract GS2-03: Prime 2 randomised trial (postoperative radiotherapy in minimum-risk elderly): Wide local excision and adjuvant hormonal therapy +/- whole breast irradiation in women =/&gt; 65 years with early invasive breast cancer: 10 year results
Authors: Kunkler Ian H , Williams Linda J , Jack Wilma , Cameron David A , Dixon Michael 
Published: February 2021

Abstract
Background: There is limited level 1 evidence on the long term outcomes after loco-regional radiotherapy after breast conserving surgery (BCS) in older patients when they are also receiving appropriate systemic therapy. Practice and guidelines vary. PRIME 2 is an international phase 3 RCT designed to address this specific question.
Methods: From April 2003 to December 2009, 1326 patients were randomised to receive (n=658) or not receive (n=668) whole breast radiotherapy (RT). Eligible patients were aged ≥ 65 years, T1-2 (up to 3cm) NO, MO, hormone receptor positive, clear excision margins (minimum 1mm), axillary node negative (pNO) receiving adjuvant hormonal therapy. Patients were eligible if they had grade 3 tumours or lymphovascular invasion but not both. The target accrual was 1300 patients based on detecting a difference in local recurrence rates between 5% in the no RT arm and 2% in the RT arm at 5 years, with 80% power and 5% significance. Ipsilateral breast tumour recurrence (IBTR) was the primary endpoint. Secondary endpoints were regional recurrence, contralateral breast cancer, distant metastases and overall survival.
Results: Median follow up is 7.3 years. At 10 years IBTR was 9.8% (95% CI 6.5, 13.2%) in the no RT arm and 0.9% (95% CI 0.1, 1.6%) in the RT arm. The hazard ratio for IBTR for those receiving RT was 0.12 (95% CI 0.05, 0.31)(p&lt;0.0001). Significant differences were found in regional recurrence (2.3% no RT vs 0.5% RT (p=0.014), but not in contralateral breast cancer (1.0% no RT, 2.2% RT, p=0.20) or distant metastases (1.4% no RT, 3.6% RT, p=0.07). Breast cancer free survival was 12.7% (95% CI 9.1, 16.2%) for the no RT arm and 6.6% (95% CI 4.1, 9.1%) for the RT arm. Breast specific survival: no RT 98.2% (95% CI 96.9, 99.4%; RT 97.8% (95% CI 96.0,99.5%) p=0.91. Overall survival at 10 years was 80.4% (95% CI 76.4, 84.5%) without RT and 81.0% (95% CI 76.7, 85.3%) with RT (p=0.68), with most deaths (80/88 no RT vs 76/79 RT) not linked to breast cancer recurrence with no influence of RT (p=0.17). Causes of death are shown in Table.
Conclusions: 10 year follow data from the PRIME 2 trial shows that the omission of RT after BCS in women aged ≥ 65 years with T1-2, pN0 hormone receptor positive breast cancer results in only 9.8% IBTR. While this rate is significantly reduced by RT (to 0.9%), the absolute reduction is modest, and there were no differences in the secondary endpoints of distant metastases, contralateral breast cancer or overall survival and a small but significant difference in regional recurrence. These data suggest that postoperative radiotherapy in this patient group who are receiving adjuvant hormonal therapy does not impact on overall survival in the context of modern approaches to local and systemic adjuvant therapy, with most patients in both arms dying of causes unrelated to breast cancer or its treatment.
Cause of deathNo RTRTTotalCancer25 (28%)29 (37%)54Of which breast cancer8 (9%)3 (4%)11Cardio-vascular9 (10%)14 (18%)23Other/unknown54 (61%)36 (45%)90Total8879167
Citation Format: Ian H Kunkler, Linda J Williams, Wilma Jack, David A Cameron, Michael Dixon. Prime 2 randomised trial (postoperative radiotherapy in minimum-risk elderly): Wide local excision and adjuvant hormonal therapy +/- whole breast irradiation in women =/&gt; 65 years with early invasive breast cancer: 10 year results [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr GS2-03.