KEY POINTS
- SUPREMO randomized 1,679 women with intermediate-risk breast cancer after mastectomy to chest wall radiotherapy (n=845) or no radiotherapy (n=834). The UK quality-of-life substudy enrolled 989 patients, with 947 baseline questionnaires and 620 expected five-year questionnaires returned.
- Eligibility included pT1–2N1, pT3N0, or pT2N0 with grade 3 disease and/or lymphovascular invasion. Radiotherapy delivered 40–50 Gy in 15–25 fractions; importantly, 69% of substudy patients receiving radiotherapy were treated with the now-familiar 40 Gy in 15 fractions.
- Chest wall symptoms were modestly worse with radiotherapy over follow-up (effect estimate 1.99, 95% CI 0.36–3.62; p=0.017), although symptoms improved between years 1, 2 and 5. At five years, mean symptom scores were 12.0 with radiotherapy versus 9.9 without radiotherapy.
- The proportion experiencing a clinically meaningful worsening of chest wall symptoms narrowed over time: 16% versus 11% at year 1, 15% versus 11% at year 2, and 13% versus 9% at year 5 for radiotherapy versus no radiotherapy.
- Radiotherapy produced no statistically significant adverse effect on arm or shoulder symptoms, body image, fatigue, pain, global quality of life, physical functioning, anxiety or depression. Reconstruction also showed no significant interaction with radiotherapy for the primary quality-of-life outcomes.
- Chemotherapy was associated with less improvement in chest wall symptoms (effect estimate 2.97, 95% CI 0.24–5.71; p=0.033), but there was no interaction with radiotherapy, so the study does not show that chemotherapy magnified the radiotherapy effect itself.
- A prespecified surgical subgroup was notable: patients who underwent sentinel node biopsy followed by axillary clearance had significantly worse chest wall symptoms with radiotherapy than without it (difference −5.29, 95% CI −8.53 to −2.05; p=0.0015). This interaction is clinically interesting but comes from a subgroup analysis.
- These quality-of-life findings sit alongside the previously reported main SUPREMO result of no 10-year overall-survival benefit and less than a 2% absolute reduction in chest wall recurrence. However, the substudy did not include modern 26 Gy in five fractions, so direct extrapolation to current ultrahypofractionated practice is uncertain.
CLINICAL TAKEAWAY
For intermediate-risk patients after mastectomy, chest wall radiotherapy produced a small persistent increase in local symptoms but no meaningful deterioration across most broader quality-of-life domains. Together with the main SUPREMO efficacy results, these data strengthen individualized shared decision-making around omission, rather than suggesting that quality-of-life toxicity alone should determine treatment.