The SUPREMO randomised, controlled, phase 3 trial evaluated the role of adjuvant chest wall radiotherapy after mastectomy in women with intermediate-risk breast cancer. The primary trial previously reported no effect on 10-year overall survival. The UK quality-of-life (QOL) substudy examined patient-reported outcomes at baseline and at 1, 2, 5, and 10 years after randomisation. This report presents the prespecified 5-year QOL results, including predefined subgroup analyses.
SUPREMO was an international, parallel-group, randomised phase 3 trial. Eligible women were aged 18 years or older with intermediate-risk breast cancer, defined as pT1-2N1, pT3N0, or pT2N0 with histological grade 3 disease or lymphovascular invasion or both. All participants had undergone mastectomy with axillary surgery. Patients were randomised 1:1 to receive chest wall radiotherapy or no radiotherapy. Radiotherapy dose regimens were 40–50 Gy delivered in 15–25 fractions. Randomisation used permuted blocks with varying block length, stratified by centre, and was open-label for patients and investigators.
All UK trial participants were invited to join the QOL substudy. Consenting patients completed validated questionnaires before randomisation and at 1, 2, 5, and 10 years. The QOL substudy's prespecified primary outcomes included global QOL, fatigue, physical function, chest wall symptoms, shoulder and arm symptoms, body image, anxiety, and depression. Analyses used intention-to-treat principles and repeated measures mixed-effects models to examine differences between treatment groups over time.
The substudy used several validated patient-reported outcome measures: the European Organisation for Research and Treatment of Cancer Quality of Life Core 30-item questionnaire (EORTC QLQ-C30), the EORTC Quality of Life Questionnaire–Breast Cancer Module (QLQ-BR23), the Body Image Scale, and the Hospital Anxiety and Depression Scale. Assessments were performed at baseline (pre-randomisation), and at 1, 2, 5, and 10 years post-randomisation. This report focuses on the 5-year timepoint.
The prespecified primary QOL endpoints were analysed using repeated measures mixed-effects models in the intention-to-treat population. The report provides effect estimates with 95% confidence intervals and p values for differences between the chest wall radiotherapy and no-radiotherapy groups, and for interactions with other treatments such as chemotherapy or surgical approach.
Between Aug 4, 2006, and April 29, 2013, SUPREMO recruited 1,691 patients overall; 1,679 were randomised to chest wall radiotherapy (n=845) or no radiotherapy (n=834). From UK centres, 1,233 patients were eligible for the QOL substudy (619 randomised to radiotherapy, 614 to no radiotherapy). Of these, 989 (80%) consented to QOL follow-up and 947 (96% of consenters) returned baseline questionnaires. At year 5, 620 of 832 expected questionnaires were returned, representing a 75% return rate for the anticipated respondents.
At 5 years, patients assigned to chest wall radiotherapy reported worse chest wall symptoms compared with those who did not receive radiotherapy. The reported effect estimate for chest wall symptoms was 1.99 (95% CI 0.36 to 3.62; p=0.017). Symptoms in the radiotherapy group showed improvement between years 1, 2, and 5.
No statistically significant differences were observed between treatment groups at 5 years for the other prespecified QOL domains: arm or shoulder symptoms, body image, fatigue, pain, overall quality of life, physical functioning, anxiety, and depression. These findings indicate that, aside from chest wall toxicity, the measured aspects of patient-reported functioning and wellbeing were similar between groups at the 5-year assessment.
The substudy examined prespecified subgroups and interactions. Chemotherapy was associated with less improvement in chest wall symptoms over time (effect estimate 2.97, 95% CI 0.24 to 5.71; p=0.033), although there was no statistical interaction between chemotherapy and radiotherapy assignment reported.
A notable surgical subgroup finding concerned axillary management: patients who underwent an initial sentinel lymph node biopsy followed by axillary lymph node clearance and received chest wall radiotherapy reported worse chest wall symptoms compared with those who had a single axillary procedure. The difference (radiotherapy vs no radiotherapy) in this subgroup was −5.29 (95% CI −8.53 to −2.05; p=0.0015), indicating a clinically relevant detriment in chest wall symptoms associated with the combined surgical and radiotherapy approach.
At 5 years, the SUPREMO QOL substudy shows that adjuvant chest wall radiotherapy after mastectomy is associated with increased chest wall toxicity but does not adversely affect the other measured QOL domains including general quality of life, physical functioning, body image, fatigue, pain, or psychological symptoms. Chest wall symptoms improved between years 1 and 5, suggesting partial recovery over time, but remained statistically worse in the radiotherapy group at year 5.
The subgroup analyses raise concerns about additional adverse QOL effects when radiotherapy is combined with certain surgical approaches (axillary clearance after sentinel node biopsy) and when chemotherapy is administered, with chemotherapy associated with less symptom improvement over time. These findings may inform multidisciplinary decision-making about adjuvant treatment sequencing and the potential trade-offs between locoregional control strategies and longer-term patient-reported toxicity.
The report focuses on 5-year outcomes; results at 10 years and longer-term impacts were not presented in this abstract. Clinicians should interpret subgroup findings cautiously and consider them in the context of overall clinical benefit, survival results, and patient preferences.
The study was funded by the UK Medical Research Council, National Institute for Health and Care Research, the European Organisation for Research and Treatment of Cancer, Edinburgh Trustees of the Breast Cancer Institute and the Edinburgh Cancer Centre NHS Endowment funds, the Dutch Cancer Society, and other trustees. Conflicts of interest are disclosed for several authors as reported in the trial abstract. Trial registration: ISRCTN61145589.