Pre-Operative Radiotherapy and Deep Inferior Epigastric Perforator Flap Reconstruction - II Trial (PRADA-II Trial)

Research question

Is preoperative radiotherapy superior to postoperative radiotherapy in improving patient-reported satisfaction with autologous breast reconstruction, 2-years following surgery? Background

Research into novel treatment sequences to improve quality of life for patients undergoing breast reconstruction and radiotherapy ranked as a high priority in a James Lind Alliance partnership and in NICE guidance. Of ~15,000 women undergoing mastectomy each year in the United Kingdom (UK), ~2000 receive autologous breast reconstruction. If radiation is required after surgery to improve disease control, several problems arise.

Radiation damages reconstructions causing pain and stiffness due to fibrosis (RR=35) and contracture (RR=11), volume loss and asymmetry (RR=8) leading to poor breast-related quality of life. Critically, ~30% of doctors do not offer immediate reconstruction when radiation is required. These women are left flat chested for on average ~50 weeks and some idefinitely.

Evidence suggests that preop radiation to the breast may improve patients’ quality of life and shorten the treatment journey but an RCT is urgently required to confirm these benefits. Aims and objectives

The main aim is to determine whether preop radiation prior to autologous breast reconstruction is superior to postop radiation in patient-reported satisfaction with their breasts at 2-years. Feasibility to recruit will be assessed with an internal pilot. Methods

We will conduct an RCT in ~26 reconstructive centres spaning the UK, recruiting from diverse socioeconomic and ethnic groups. After consent, locally advanced breast cancers requiring mastectomy and suitable for microvascular reconstruction will be randomly allocated to either preop or postop radiation. Breast-related quality of life will be measured using validated questionnaires (BREAST-Q).

The primary outcome is BREAST-Q satisfaction with the breast, 2-years following surgery. We will also measure general quality of life (EQ-5D-5L), validated expert panel assessment of cosmesis (Visser scale), perioperative complications (e.g. skin necrosis, reconstruction failures, etc), oncologic outcomes (recurrence, survival, etc) and treatment time (days).

Costs and cost savings for the NHS will be measured. Process evaluation will identify barriers, enablers and facilitators to adoption of preop radiation. Timelines for delivery

The study will last 6.25-years in total. After 9 months of study set-up and opening sites, a pilot for 12 months will be conducted to evaluate recruitment and if necessary, mitigation plans to increase accrual. The main phase will recruit over 24 months with 24 months follow-up. The final 6 months will be for used database queries and database lock, as well as analyses and writing reports.

Dissemination and Impact

Results will be disseminated in publications, presentations and via national and international associations and networks of breast, plastic and reconstructive surgeons, and to patients via a dedicated trial website, webinar and video. If this work shows benefit, there will be national support to change practice to improve reconstructive outcomes, enhance quality of life and shorten the treatment journey.

Practice change would lead to substantial health economic benefits and improve access for patients to the quality of life benefits of immediate reconstruction. Preop radiation will be written into national best practice guidelines for oncoplastic breast surgery.