The QUEST study: a multicentre randomised trial to assess the impact of the type and timing of breast reconstruction on quality of life following mastectomy

Background

Breast reconstruction is performed to improve the quality of life and body image for women facing mastectomy. Whilst significant anecdotal evidence and surgical dogma exists regarding the optimal reconstructive practice, a comprehensive MEDLINE literature review has revealed a paucity of well designed, statistically powered studies to address the impact of either the type or the timing of breast reconstruction on these key patient-reported outcomes. There is little high-quality evidence to support the benefit of immediate versus delayed breast reconstruction, for example, or to suggest the superiority of autologous over implant-assisted reconstructions in terms of improvements in quality of life or body image, particularly in the context of postoperative radiotherapy (RT). There is also very limited evaluation of the impact of latissimus dorsi (LD) breast reconstruction, although this is the procedure most commonly offered by oncoplastic breast surgeons in the UK. There is currently, therefore, very little to guide patients or their surgeons in making important decisions regarding their reconstructive options.

Study aim

The Quality of Life following Mastectomy and Breast Reconstruction (QUEST) study aims to apply rigorous scientific methodology to definitively address causality and to address key reconstructive questions, thus ultimately providing patients and their surgeons with high-quality evidence as the basis for truly informed consent.

Study design

The QUEST study is the first multicentre statistically powered randomised controlled trial to assess the impact of the type and timing of the most commonly offered form of breast reconstruction on quality of life following mastectomy. The study consists of two parallel randomised controlled trials, with study entry determined by a preoperative assessment of the requirement for postoperative RT (see Figure 1). Women unlikely to require postoperative RT will be randomised to either autologous or implant-assisted LD breast reconstruction, while those requiring RT will be randomised to either immediate or delayed extended LD procedures. These approaches are consistent with current accepted reconstructive practice. The use of a randomised methodology in the context of patient-centred procedures of this kind has been much criticised on the basis of additional patient stress and the view that patients who consent to randomisation are likely to differ significantly from the population as a whole, thus limiting the generalisability of the results. The QUEST study, however, addresses this issue by recruiting patients declining or not eligible for randomisation to a prospective cohort study, thus creating a comprehensive cohort and allowing the impact of the decision-making process to be assessed.

Figure 1

The QUEST study flow chart. ADH, atypical ductal hyperplasia; DCIS, ductal carcinoma in situ; ELD, extended latissimus dorsi; LCIS, lobular carcinoma in situ. *Prospective patients will undergo preoperative evaluation of the breast (mammogram/ultrasound scan/MRI and core biopsy) and axilla (ultrasound scan and fine-needle aspiration of suspicious nodes or preoperative sentinel lymph node biopsy) to determine whether they are likely to require postoperative radiotherapy (RT) according to each centre's local RT guidelines (for example, multifocality, grade 3, lymphovascular invasion and nodal involvement). **Delayed reconstructions must be performed within 12 months of randomisation. ***Patients in the delayed arm will complete baseline questionnaires prerandomisation and at 3 months and 6 months post mastectomy, then prereconstruction (usually approximately 12 months postoperative). Following reconstruction, follow-up will be as per the other arms – 3 months, 6 months, 12 months and annually for 5 years.

Patients

Women requiring mastectomy for invasive breast cancer, ductal carcinoma in situ, atypical ductal hyperplasia, lobular carcinoma in situ or other premalignant condition who request LD breast reconstruction are eligible for inclusion in the study.

Sample size

A power calculation has suggested that 150 patients will be required in each study arm to detect an effect size of 0.4 at the 5% level with 90% confidence. As a randomised trial in breast reconstruction is a challenging prospect, the main study will be preceded by a 12-month feasibility study of the same design to assess patient recruitment to each study arm.

Conclusion

As the survival rate from breast cancer increases, quality of life becomes an increasingly significant outcome. This is an exciting, innovative and challenging project, but it is only through the use of rigorous scientific methodology that definitive evidence can be produced. Women facing mastectomy deserve truly informed decision-making regarding their reconstructive options. This is the QUEST.