Adjuvant radiotherapy does not impact overall survival and loco-regional recurrence beyond ten years of follow-up in patients with early breast cancer

Adjuvant radiotherapy after breast-conserving surgery (BCS) is thought to improve long-term survival by preventing local recurrences in breast cancer. The Scottish Conservation trial followed breast cancer patients who underwent BSC and received systemic therapy with or without radiotherapy (RT) for up to 30 years. The outcomes challenged the standard idea, showing that adjuvant RT only reduces local recurrences in the first 10 years of follow-up, but has no impact on recurrence and overall survival thereafter.

The standard of care for most early breast cancer patients is breast-conserving surgery (BCS), adjuvant radiotherapy (RT) and systemic therapy. The Oxford meta-analysis, which included seventeen trials and 10,801 women with early breast cancer treated with BCS with or without RT, had a deep influence on the implementation of this practice. Adding RT to BCS resulted in a 15.7% reduction in first recurrence, either metastatic or local, of which most of them were local recurrences. This resulted in a modest reduction of 3.8% in breast cancer deaths. However, all these studies were focused on the first ten years of follow-up, meaning that very little is known about the impact of RT thereafter. The Scottish Conservation trial showed a loco-regional recurrence (LR, also called ipsilateral breast tumour recurrence (IBTR)) of 24.5% vs. 5.8% in patients with early breast cancer receiving BCS with or without RT at six years after randomisation, and no difference in overall survival (OS). The 30-year follow-up results of this study were presented at EBCC 2022.

Study design

The Scottish Conservation trial recruited 585 patients with early breast cancer between 1985 and 1991. Patients ≤70 years old with tumours ≤4cm (T0,T1a,T2a, N0, N1a, N1b, M0) underwent local excision with a 1cm margin, axillary node sampling or axillary node clearance. Subsequently, patients received adjuvant systemic therapy of tamoxifen or chemotherapy appropriate to the ER status. Patients were randomised (1:1) to RT vs. no RT. The analysis was undertaken based on the original primary endpoint of local recurrence and OS, and the secondary endpoints of regional recurrence, distant metastasis and breast cancer deaths. Data at 10, 20 and 30 years were compared by log-rank test. Hazard ratios (HR) were reported with no RT as the reference.

Results

In total, 291 patients received RT, while 294 did not. The two arms were well balanced for age, menopausal status, adjuvant systemic therapy, type of axillary surgery, laterality, tumour size, grade, histological type, nodal status and ER status. Around 30% of the patients were treated with chemotherapy and 70% with tamoxifen. Over the 30-year period, RT resulted to be extremely effective, reducing the risk of IBTR recurrence by 61% (HR[95%CI]: 0.39[0.27-0.55]; p< 0.0001). However, it showed a differential effect over time, and most benefit was delivered during the first ten years. After this time, less than 1% of the patients have recurrence in both the RT and no RT arms. At 10 years, there was a 22% reduction in LR in the RT arm (vs. no RT arm). Yet, after the first ten years, the annual risk of a recurrence was similar in both groups. As such, 30 years after their treatment, 23.7% of women who had radiotherapy were still alive compared to 27.5% of those who did not. Observations were similar for regional recurrence (RR), and there was no difference in the effect of RT in distant metastasis (HR[95%CI]: 0.82[0.62-1.09]; p= 0.17).

Conclusions

After a follow-up of 30 years, the Scottish Conservation trial showed that adjuvant loco-regional RT after BCS and systemic therapy appropriate to ER status reduces the risk of local recurrence during the first 10 years of follow-up, but has no impact thereafter. Remarkably, there is also no long-term improvement in OS for those women having radiotherapy. “These data challenge the idea that radiotherapy improves long-term survival by preventing recurrences of cancer in the same breast. This may be because, although radiotherapy may help to prevent some breast cancer deaths, it may also cause a few more deaths, particularly a long time after the radiotherapy, from other causes such as heart and blood vessel diseases.” 

Reference

Williams L, Taylor K, Cameron DA, et al. Randomised controlled trial of breast conserving therapy: 30 year analysis of the Scottish breast conservation trial. Presented at EBCC 2022; Abstract PPT-140.